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Background Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. Methods Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. Results All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI): 92.1%-99.0%) and 100% (95% CI: 96.4%-100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred, but unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. Conclusions SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs.

This paper proposes a millimeter-wave phased antenna array configuration, with 2D beam-switching functionality and scalability in terms of the array size and number of switchable beams. A wideband vertically installed planar transition (VIPT) works in conjunction with a flexible substrate to implement a two-stage Rotman lens and to simultaneously increase the scalability and integration space without requiring expensive RF cables and connectors. In addition, owing to the VIPT, the vertical board can be considered a replaceable component and can be replaced by different designs to satisfy different applications. Prototypes of 60 GHz phased antenna array are manufactured and measured. The measurement results confirm that the proposed array configuration can implement 32 different main beam directions with a coverage angle of 70° in terms of both elevation and azimuth. The proposed configuration is a feasible and promising approach for millimeter-wave radio applications.

Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters.We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured byBetween Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 [47%] men and 299 [53%] women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy.The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation.For the Chinese translation of the abstract see Supplementary Materials section.

Adequate bowel preparation is an essential part of a high-quality colonoscopy. Recent studies showed that the small-volume bowel cleansing agent Bowklean performs better in terms of tolerability and acceptability. However, its split-dose regimen is sometimes confusing to the patient. To promote Bowklean in Fu Jen Catholic University Hospital, dedicated staff for patient education on bowel preparation were provided by Universal Integrated Corporation (Taiwan), but not in every period because of the clinic room availability and manpower capacity. This provided us an opportunity to compare the quality of colonoscopy between those with and without the dedicated patient education. This study aimed to compare various quality indices between the two groups. We set bowel preparation quality as the primary endpoint, assessed by modified Aronchick scale, and other quality indices including procedure time and adenoma detection rate as the secondary endpoints. We performed a single institution retrospective study. All patients who received colonoscopy from an outpatient setting with Bowklean as the bowel cleansing agent from October 2020 to November 2020 were reviewed. Primary and secondary endpoints were then compared between the conventional group and the dedicated staff group, with StataSE 14 by Wilcoxon rank sum test or logistic regression. Four hundred ten patients were recruited, including 217 patients with dedicated patient education and 193 without. The proportion of bowel preparation quality "Excellent + Good + Fair" was significantly higher in dedicated staff group than conventional group (97.7% vs 93.3%, P = .03; logistic regression coefficient = 1.12). The cecal intubation time was significantly shorter in the dedicated staff group (3.68 ± 2.02 minutes vs 4.52 ± 3.25 minutes, P.01). After excluding those with polypectomy or biopsy, the total procedure time tended to be shorter in the dedicated staff group (10.2 ± 3.35 minutes vs 9.40 ± 2.43 minutes, P = .06). There was no significant difference regarding adenoma detection rate between the two groups. Our study shows that patient education by dedicated staff can improve bowel preparation quality and has the potential to decrease procedure time. Further large-scale prospective trials are still needed to evaluate if it can also achieve a better adenoma detection rate.

Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6–96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8–99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan.

The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes.Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010-2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy.319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05-4.81); aOR 1.35, 95 %CI 1.12-1.53; aOR 1.88, 95 %CI 0.61-5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90-3.32).FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes.Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010–2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy.319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05–4.81); aOR 1.35, 95 %CI 1.12–1.53; aOR 1.88, 95 %CI 0.61–5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90–3.32).FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.

This article proposes a new wideband active power splitter design where the gain cells along the input transmission line are arranged in interleaf rather than the conventional parallel style, thus the circuit's high-frequency performance can be greatly improved. Both theoretical analysis and circuit simulation have been carried out; as a demonstration, parallel and interleaf active power splitters are designed using 0.1 μm GaAs pseudo-morphic heterostructure field effect transistors (GaAs pHEMT) process and measured on-wafer. The results clearly indicate the superiority of the interleaf topology. A 40 GHz interleaf active power splitter in 90 nm complementary metal-oxide-semiconductor (CMOS) is then presented where the magnitude and phase imbalance between the two output ports are 0.15 dB and 2.6° at 20 GHz, and 0.16 dB and 14° at 40 GHz. The output-port isolation is better than 30 dB across the whole frequency range.

In this study, the authors will investigate the insertion loss (IL) of the broadband 8-way power combiner used in their millimetre-wave power amplifier (PA) design. By treating this combiner as impedance transformer under resistor-capacitor (RC)-loading condition, both the characteristic impedance and electrical length of the constituting metal lines can be obtained, where the much shorter line length suggests wider bandwidth and lower IL. However, proper loss analysis must take into account the multi-reflection of voltage wave along these mismatched transmission lines, i.e. the use of the power attenuation expression e − 2 α L is just not accurate enough. With their derived equations, it shows that the IL of their proposed 8-way combiner can be as low as 0.92 dB at 94 GHz, which is much smaller than the 1.5 dB for the conventional quarter-wavelength combiner. Mathematics for the IL of the drain-bias shunt stub and the output DC-blocking capacitor has also been derived. As a demonstration, a 77–110 GHz 40 nm-complementary metal–oxide–semiconductor PA made of cascode transistors is then designed that has more than 18 dB gain, and its OP1 dB is around 13 dBm across the whole frequency range.

In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4-86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7-88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6-92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters.This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov, NCT01906879.Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 [33%] per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p0·0001), and BQ10 (p0·0001) treatment. Beta diversity was also significantly altered 2 weeks after T14 (p=0·0010), C10 (p=0·0001), and BQ10 (p=0·0001). Alpha diversity and beta diversity were restored at week 8 (p=0·14 and p=0·918, respectively) and 1 year (p=0·14 and p=0·918) after T14, but were not fully recovered at week 8 and after 1 year in patients treated with C10 (p=0·0001 and p=0·013 at week 8; p=0·019 and p=0·064 at 1 year) and BQ10 (p0·0001 and p=0·0002; p=0·001 and p=0·029). A transient increase at week 2 after T14 and C10 of the resistance rates of E coli to ampicillin-sulbactam (12% [15/127] to 66% [38/58] for T14, 7% [10/135] to 64% [28/44] for C10), cefazolin (13% [16/127] to 43% [25/58] for T14, 10% [13/135] to 41% [18/44] for C10), cefmetazole (8% [10/127] to 26% [15/58] for T14, 4% [5/135] to 18% [8/44] for C10), levofloxacin (8% [10/127] to 35% [20/58] for T14, 7% [10/135] to 32% [14/44] for C10), gentamicin (13% [19/146] to 47% [27/58] for T14, 15% [22/149] to 45% [20/44] for C10), and trimethoprim-sulfamethoxazole (33% [48/146] to 86% [50/58] for T14, 28% [42/148] to 86% [38/44] for C10; p0·05 in paired samples in the above analyses) returned to basal state at week 8 and after 1 year. Although bodyweight and body-mass index slightly increased, there were significant improvements in metabolic parameters, with a decrease in insulin resistance, triglycerides, and LDL and an increase in HDL. Overall, there was no significant change in the prevalence of metabolic syndrome at week 8 and 1 year after T14, C10, and BQ10.Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy.National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

This manuscript presents the design of a W-band receiver in which an radio frequency-low noise amplifier (RF-LNA), a wideband mixer, intermediate frequency (IF) amplification, a local oscillator frequency (LO) tripler and a driving amplifier are all integrated into one single chip of 1050 × 820 μm 2 . To effectively extend the mixer's IF bandwidth while retaining its conversion gain, impacts of the mixing transistor's drain bias and output loading impedance are explored using a dual-modulation conversion-matrix method, which allows both the LO-induced transconductance modulation and channel-conductance modulation to be considered simultaneously. It is shown that, by merging the input capacitance of the IF amplifier into a high-impedance artificial transmission line, an actively biased mixer can have constant conversion gain over broad bandwidth. A 77–110 GHz 65 nm-complementary metal-oxide-semiconductor (CMOS) receiver with 33 GHz IF bandwidth is then designed and measured. Its conversion gain and noise figure are 10 and 20 dB, respectively, and the input-referred P1 dB is −15 dBm; the overall power consumption is 330 mW under 1.3 V drain bias.

Background Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. Methods Between July 2019 and March 2020, 1,880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. Results The SVR12 rates by EP and PP analyses were 95.6% (1,798 of 1,880 patients; 95% confidence interval (CI): 94.6%-96.5%) and 99.3% (1,798 of 1,811 patients; 95% CI: 98.8%-99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1,859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. Conclusions SOF/VEL for 12 weeks is efficacious and well-tolerated chronic HCV-infected patients with compensated liver disease in Taiwan.

BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus (BE), making standardization challenging. AIM To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists. METHODS Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE. RESULTS Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001). CONCLUSION Diagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

ObjectiveData regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5.Design191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR12) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed.ResultsThe SVR12 rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR12 rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR12 rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR12 were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations.ConclusionSOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.

Background There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB). Aim To investigate if hepatitis B core-related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation. Methods This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2 months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score. Results During a median follow-up of 25.9 months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5-year cumulative incidence of 56.1% (95% CI 46.7-66.0%) and 8.8% (95% CI 4.3-17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE-B) was calculated by the equation of 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2*age (year) + ALT (U/L) + 40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5 years, respectively. Moreover, HBsAg loss occurred exclusively in low-risk patients predicted by the score. Conclusions Serum HBcrAg and HBsAg levels were independent predictors of off-NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.

A multiphase all-digital crystal-less clock generator (CLCG) with an interpolating digital controlled oscillator (DCO) that achieves an operating frequency of 500 MHz with 10-phase outputs is proposed. The CLCG adopts a specific temperature coefficient of a time-to-digital convertor (TDC) to create a positive or negative temperature coefficient and compensates for the DCO frequency drift. A time amplifier (TA) can extend the timing resolution of the TDC and reduce the effects of process variations in order to tune the TA gains. The frequency compensator adopts the frequency difference between the ring oscillator and DCO to reduce the frequency drift. The frequency accuracy is 69 ppm/°C from - 20 to 80°C. The root mean square jitter and output phase noise are 3.86 ps and - 100.36 dBc/Hz at 1 MHz, respectively. The core area of the test chip is 350 × 420 μm 2 in a 65-nm CMOS process. At a supply voltage of 0.6 V, the power consumption is 1.8 mW for the 5 Gb/s clocking system.

Background & Aims We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. Methods We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. Results H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance–guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. Conclusions Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

Introduction and aim. In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB. Material and methods. We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA > 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated. Results. According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53-0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure. Conclusions. A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.

Exact synthesis of unequal power division filtering rat-race ring couplers is proposed. The power division property results from the half-symmetric core ring structure of the proposed couplers. The proposed core ring was modified from the equal power division rat-race ring in 2015 where the core ring in that circuit is fully symmetric. Due to the half-symmetry of ring and unequal power division characteristics, the signal excitation and circuit partition methods in 2015 cannot be applied. In this paper, the modified signal-excitation method and the source-division technique are proposed to reduce the original four-port rat-race ring couplers into the corresponding two-port networks. These two-port networks can be exactly synthesized by the S-domain filter synthesis method. Alternatively, the simplified design equations are proposed. Using these equations, the rat-race ring hybrid in 2015 can be transformed into the arbitrary power division rat-race ring couplers. Therefore, the final rat-race ring couplers are provided with some user-defined specifications, such as the unequal power division, the input/output impedance transformation, the center frequency, the fractional bandwidth, and the return loss level. Two fifth-order filtering rat-race ring couplers with 3- and 10-dB power division are implemented as examples; in addition, these couplers are with a center frequency of 2 GHz, a fractional bandwidth of 100%, a return loss level of 20 dB, and the input/output impedance transformation of 50/70 $\Omega $ . The measured and simulated results indicate good agreement.

This paper presents high-isolation single-pole-single-throw (SPST) and single-pole-double-throw (SPDT) substrate integrated waveguide (SIW) mechanical switches in $V$ - and $W$ -bands. Four via holes with the proposed ring-and-cross etching patterns on the top side are placed in the middle of SIW path to block or pass the waves. As the ring-and-cross etching patterns being short-circuited, the via holes block the waves just like stockades do, in other words, turning the switch to OFF mode. And the ring-and-cross etching pattern makes the via holes invisible, turning the switch to ON mode. The $V$ - and $W$ -band SIW SPST and SPDT switches are designed and fabricated. The switches show the measured performances of better than 45-dB isolation for SPST and better than 50-dB isolation for SPDT, for $V$ -band operation, and a better than 50-dB isolation for both SPST and SPDT for $W$ -band operation.

BACKGROUND AND AIM Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain. METHODS A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations. RESULTS The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P

Background Endoscopic radiofrequency ablation (RFA) is a treatment option for early esophageal squamous cell neoplasia (ESCN); however, long-term follow-up studies are lacking. The risks of local recurrence and “buried cancer” are also uncertain. Methods Patients with flat-type ESCN who were treated with balloon-type ± focal-type RFA were consecutively enrolled. Follow-up endoscopy was performed at 1, 3, and 6 months, and then every 6 months thereafter. Endoscopic resection was performed for persistent and recurrent ESCN, and the histopathology of resected specimens was assessed. Results A total of 35 patients were treated with RFA, of whom 30 (86 %) achieved a complete response, three were lost to follow-up, and five (14 %) developed post-RFA stenosis. Two patients had persistent ESCN and received further endoscopic resection, in which the resected specimens all revealed superficial submucosal invasive cancer. Six of the 30 patients with successful RFA (20 %) developed a total of seven episodes of local recurrence (mean size 1.4 cm) during the follow-up period (mean 40.1 months), all of which were successfully resected endoscopically without adverse events. Histological analysis of the resected specimens revealed that six (86 %) had esophageal glandular ductal involvement, all of which extended deeper than the muscularis mucosae layer. Immunohistochemistry staining for P53 and Ki67 suggested a clonal relationship between the ductal involvement and epithelial cells. None of the tumors extended out of the ductal structure; no cases of cancer buried beneath the normal neosquamous epithelium were found. Conclusions Because ductal involvement is not uncommon and may be related to recurrence, the use of RFA should be conservative and may not be the preferred primary treatment for early ESCN.

This Letter presents a fully integrated bio-system with the property of high sensitivity for electrochemical detection, which can intrinsically measure electrochemical characteristics with cyclic voltammetry. In normal circumstances, ultra-low electrolytes exist in tissue solution, which is difficult to accurately detect the oxidation/reduction signals, limited by the innate circuit and liquid noise. Hence, the conventional topology of the potentiostat circuit is improved and proposed in this Letter to remove the required analogue-to-digital converter (ADC). The overall operational mechanism of the potentiostat behaves like a single-slope ADC, which achieves a compact, easily implemented, and low-noise design. Additionally, the effective capacitance of potentiostat and liquid resistance make an RC integration to further suppress out-of-band noise, thereby enabling the low-electrolyte detection and improving detecting sensitivity. To simulate the low-electrolyte environment, only 0.01 M ( M = mol/l) phosphate buffered saline background solution is used and required to demonstrate its feasibility of the concept. The measured results show the sensor chip with high sensitivity to sense resistive variation of electrochemical action in low electrolytes.

Background & Aims Endoscopic papillary balloon dilation (EPBD) is an alternative to endoscopic sphincterotomy for choledocholithiasis. Unlike endoscopic sphincterotomy, EPBD preserves biliary sphincter function, reducing long-term risk of recurrent choledocholithiasis by 50%. Guidelines recommend that duration of EPBD exceeds 2 minutes, to adequately loosen the sphincter and reduce risks of failed stone extraction and post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, it is unclear whether this long duration of EPBD impairs sphincter function and negates the long-term benefit of EPBD. We performed a randomized controlled trial to determine whether long-duration (>1 minute) EPBD increases the risk of subsequent choledocholithiasis and hepatobiliary complications compared with short-duration EPBD ( Methods We performed a prospective study of 170 adult patients who underwent ERCP for suspected choledocholithiasis from April 2007 through October 2008 at 2 centers in Taiwan. Patients were randomly assigned to groups that underwent 1-minute (n = 86) or 5-minute (n = 84) EPBD for choledocholithiasis; patients were followed through June 2015. One month after the initial ERCP, patients were examined and liver function tests and abdominal sonographies were performed. Patients were then examined every 3–6 months over a median follow-up period of approximately 7 years. The primary outcome was recurrent choledocholithiasis or acute cholangitis and the secondary outcome was overall hepatobiliary complications. We assessed the effects of EPBD duration by Cox regression. Results Thirteen patients (15.1%) developed recurrent choledocholithiasis or acute cholangitis after 1-minute EPBD, and 10 patients (11.9%) developed recurrent choledocholithiasis or acute cholangitis after 5-minute EPBD ( P = .352). There was no significant difference between groups in number of hepatobiliary complications ( P = .154). Compared with 1-minute EPBD, 5-minute EPBD did not increase risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval, 0.32–1.82) or the secondary outcome (adjusted hazard ratio, 0.65; 95% confidence interval, 0.31–1.40). Mechanical lithotripsy, performed for failed stone extraction with EPBD at initial ERCP, was a risk factor for primary and secondary outcomes. Conclusions In a randomized controlled trial, we found that the risk of recurrent choledocholithiasis and hepatobiliary complications did not increase with long-duration EPBD (>1 minute), but was increased with mechanical lithotripsy.

Accumulating data has revealed a rapidly rising incidence of pancreatic cancer in Western countries, but convincing evidence from the East remains sparse. We aimed to quantify how the incidence and mortality rates of pancreatic malignancy changed over time in Taiwan, and to develop future projection for the next decade.This nationwide population-based study analyzed the Taiwan National Cancer Registry and the National Cause of Death Registry to calculate the annual incidence and mortality rates of pancreatic malignancy from 1999 to 2012 in this country. The secular trend of the incidence was also examined by data from the National Health Insurance Research Database.A total of 21,986 incident cases of pancreatic cancer and 20,720 related deaths occurred during the study period. The age-standardized incidence rate increased from 3.7 per 100,000 in 1999 to 5.0 per 100,000 in 2012, with a significant rising trend (P0.01). The increase was nationwide, consistently across subgroups stratified by age, gender, geographic region, and urbanization. Data from the National Health Insurance Research Database corroborated the rise of incident pancreatic cancer. Mortality also increased with time, with the age-standardized rate rising from 3.5 per 100,000 in 1999 to 4.1 per 100,000 in 2012 (P0.01). In accordance with the incidence, the mortality trend was consistent in all subgroups. Both the incidence and mortality were projected to further increase by approximately 20% from 2012 to 2027.The incidence and mortality of pancreatic cancer have been rapidly rising and presumably will continue to rise in Taiwan.