Chronic hepatitis C virus (HCV) infection is increasingly observed in patients with renal disease. With the introduction of glecaprevir/pibrentasvir (GLE/PIB) as a pan-genotype therapy for HCV, ...treatment efficacy is expected to rise.
This retrospective study evaluated the efficacy and safety of GLE/PIB treatment in adults with HCV infection and end-stage renal disease (ESRD). The primary end point was sustained virological response (SVR) observed 12 weeks after completed treatment.
We enrolled 235 patients, including 44 patients with ESRD. Median age was 60 years, and 48% were males. Twenty-two percent had cirrhosis. HCV genotypes 1 (43%) and 2 (41%) were the most common. The overall SVR rate was 96.6%. Patients with ESRD were older than those without (67.6 years vs 58.3 years, p < 0.001) and trended toward having a higher prevalence of cirrhosis (32% vs 19%, p = 0.071). A significant proportion of patients with ESRD complained of skin itching during treatment (61% vs 26%, p < 0.001), and the SVR rate were similar between these two groups (95.45% vs 96.86%, p = 0.644).
Despite a higher rate of pruritus among patients with ESRD, GLE/PIB-based therapy achieved similarly high SVR rates among patients with and without ESRD.
It is known that the risk of dementia in patients with moderate to severe traumatic brain injury (TBI) is higher. However, the relationship between mild traumatic brain injury (mTBI) and dementia has ...never been established.
We investigated the incidences of dementia among patients with mTBI in Taiwan to evaluate if there is higher risk compared with general population.
We utilized a sampled National Health Insurance (NHI) claims data containing one million beneficiaries. We followed all adult beneficiaries from January 1, 2005 till December 31, 2009 to see if they had been diagnosed with dementia. We further identify patients with mTBI and compared their risk of dementia with the general population.
We identified 28551 patients with mTBI and 692382 without. After controlled for age, gender, urbanization level, socioeconomic status, diabetes, hypertension, coronary artery disease, hyperlipidemia, history of alcohol intoxication, history of ischemic stroke, history of intracranial hemorrhage and Charlson Comorbidity Index Score, the adjusted hazard ratio is 3.26 (95% Confidence interval, 2.69-3.94).
TBI is an independent significant risk factor of developing dementia even in the mild type.
Contact tracing for containing emerging infectious diseases such as COVID-19 is resource intensive and requires digital transformation to enable timely decision-making. This study demonstrates the ...design and implementation of digital contact tracing using multimodal health informatics to efficiently collect personal information and contain community outbreaks. The implementation of digital contact tracing was further illustrated by 3 empirical SARS-CoV-2 infection clusters. The implementation in Changhua, Taiwan, served as a demonstration of the multisectoral informatics and connectivity between electronic health systems needed for digital contact tracing. The framework incorporates traditional travel, occupation, contact, and cluster approaches and a dynamic contact process enabled by digital technology. A centralized registry system, accessible only to authorized health personnel, ensures privacy and data security. The efficiency of the digital contact tracing system was evaluated through a field study in Changhua. The digital contact tracing system integrates the immigration registry, communicable disease report system, and national health records to provide real-time information about travel, occupation, contact, and clusters for potential contacts and to facilitate a timely assessment of the risk of COVID-19 transmission. The digitalized system allows for informed decision-making regarding quarantine, isolation, and treatment, with a focus on personal privacy. In the first cluster infection, the system monitored 665 contacts and isolated 4 (0.6%) cases; none of the contacts (0/665, 0%) were infected during quarantine. The estimated reproduction number of 0.92 suggests an effective containment strategy for preventing community-acquired outbreak. The system was also used in a cluster investigation involving foreign workers, where none of the 462 contacts (0/462, 0%) tested positive for SARS-CoV-2. By integrating the multisectoral database, the contact tracing process can be digitalized to provide the information required for risk assessment and decision-making in a timely manner to contain a community-acquired outbreak when facing the outbreak of emerging infectious disease.
Background/Aims In a recent study, attenuation imaging (ATI) with ultrasound was used as a new approach for detecting liver steatosis. However, although there are many studies on ATI and controlled ...attenuation parameter (CAP) that prove their practicability, there are few studies comparing these two methods. As such, this study compared CAP and ATI for the detection and evaluation of liver steatosis. Methods A prospective analysis of 28 chronic liver disease patients who underwent liver biopsy, FibroScan® imaging, and ATI with ultrasound was conducted. The presence and degree of steatosis, as measured with the FibroScan® device and ATI, were compared with the pathological results obtained using liver biopsy. Results The areas under the receiver operating characteristic curve (AUROC) of ATI and CAP for differentiating between normal and hepatic steatosis were 0.97 (95% confidence interval CI 0.83-1.00) and 0.96 (95% CI 0.81-0.99), respectively. ATI has a higher AUROC than CAP does in liver steatosis, at 0.99 (95% CI, 0.86-1.00) versus 0.91 (95% CI, 0.74-0.98) in grade greater than or equal to 2 and 0.97 (95% CI, 0.82-1.00) versus 0.88 (95% CI, 0.70-0.97) in grade = 3, respectively. Conclusion The ATI and CAP results showed good consistency and accuracy for the steatosis grading when compared with the liver biopsy results. Moreover, ATI is even better than CAP in patients with moderate or severe steatosis. Therefore, ATI represents a non-invasive and novel diagnostic tool with which to support the diagnosis of liver steatosis in clinical practice.
Many patients with chronic hepatitis B (CHB) are classified as indeterminate patients because they fall outside the defined CHB phases. We aimed to explore hepatocellular carcinoma (HCC) risk in ...hepatitis B e antigen (HBeAg)-negative patients with indeterminate phase and investigated whether the risk could be stratified by serum levels of hepatitis B core-related antigen (HBcrAg).
Two retrospective cohorts enrolling HBeAg-negative, treatment-naïve CHB patients without cirrhosis were constructed (N = 2,150 in Taiwanese discovery cohort and N = 1,312 in Japanese validation cohort with a mean follow-up period of 15.88 and 12.07 years, respectively). The primary end point was HCC development.
According to the American Association for the Study of Liver Disease guidelines, 990 (46%) HBeAg-negative patients had indeterminate CHB phase at baseline in the Taiwanese cohort. Compared with the patients with inactive CHB and those with immune-active CHB, the indeterminate patients exhibited intermediate but diverse risk of HCC. When HCC risk was stratified by a HBcrAg level of 10,000 U/mL, 10-year HCC cumulative incidence was 0.51% and 5.33% for low HBcrAg and high HBcrAg groups, respectively, with a hazard ratio of 4.47 (95% confidence interval: 2.62-7.63). This cutoff was validated to stratify HCC risk not only in different subgroup analyses but also in an independent Japanese cohort. Finally, the overall HBeAg-negative CHB patients could be simply reclassified into high-risk and low-risk groups by combining ALT, hepatitis B virus DNA, and HBcrAg levels in both cohorts.
Serum HBcrAg level of 10,000 U/mL stratifies HCC risk in HBeAg-negative patients with indeterminate phase, which is useful for optimizing their clinical management.
DNA methylation is an epigenetic modification that plays an important role in regulating gene expression and therefore a broad range of biological processes and diseases. DNA methylation is ...tissue-specific, dynamic, sequence-context-dependent and trans-generationally heritable, and these complex patterns of methylation highlight the significance of profiling DNA methylation to answer biological questions. In this review, we surveyed major methylation assays, along with comparisons and biological examples, to provide an overview of DNA methylation profiling techniques. The advances in microarray and sequencing technologies make genome-wide profiling possible at a single-nucleotide or even a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, genomic region coverage, and bioinformatics analysis, and selecting a feasible method requires knowledge of these methods. We first introduce the biological background of DNA methylation and its pattern in plants, animals and fungi. We present an overview of major experimental approaches to profiling genome-wide DNA methylation and hydroxymethylation and then extend to the single-cell methylome. To evaluate these methods, we outline their strengths and weaknesses and perform comparisons across the different platforms. Due to the increasing need to compute high-throughput epigenomic data, we interrogate the computational pipeline for bisulfite sequencing data and also discuss the concept of identifying differentially methylated regions (DMRs). This review summarizes the experimental and computational concepts for profiling genome-wide DNA methylation, followed by biological examples. Overall, this review provides researchers useful guidance for the selection of a profiling method suited to specific research questions.
Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). Serum levels of HB core–related antigen (HBcrAg) have been associated with active replication of HBV. We ...investigated whether HBcrAg levels are associated with development of HCC, especially in patients who do not require antiviral treatment.
We collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C, and without liver cirrhosis, who had long-term follow-up at the National Taiwan University Hospital from 1985 through 2000. None of the patients received antiviral treatment during the follow-up. Baseline levels of HBV DNA, HBsAg, and HBcrAg were determined retrospectively and participants were followed for a mean of 15.95 years. The primary end point was an association between serum level of HBcrAg and HCC development.
HCC developed in 209 patients in the cohort (incidence rate, 4.91 cases/1000 person-years). We found a positive association between baseline level of HBcrAg and HCC development; HBcrAg level was an independent risk factor in multivariable analysis. In the subgroup of hepatitis B e antigen–negative patients with HBV DNA levels from 2000 to 19,999 IU/mL (intermediate viral load IVL) and normal levels of alanine aminotransferase, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 6.29; confidence interval, 2.27–17.48). Patients with an IVL and a high level of HBcrAg had a risk for HCC that did not differ significantly from that of patients with a high viral load (≥20,000 IU/mL). Patients with an IVL but a low level of HBcrAg had a low risk of HCC, with an annual incidence rate of 0.10% (95% confidence interval, 0.04%–0.24%).
In a long-term follow-up study of 2666 patients with chronic HBV infection (genotypes B or C), level of HBcrAg is an independent risk factor of HCC. Moreover, HBcrAg level of 10 KU/mL identifies patients with an IVL who are at high risk for HCC.
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Bromotrimethylsilane‐promoted benzannulation of o‐alkynylbenzaldehydes and alkynes to yield 1‐naphthyl aryl ketones is reported. The reaction conditions are mild, metal‐free, and do not require ...pretreatment/protection of the substrates. We found that aryl propargyl alcohols were very effective substrates for this reaction, compared with other alkynes. Studies on the reaction scope, monitoring the reaction progress by 1H NMR, and theoretical calculations suggest that isochromenylium (benzopyrilium) ion is the key reaction intermediate.
Background
To assess the impact of treatment delay on survival of oral/oropharyngeal cancer (OSCC).
Methods
We followed 5743 OSCCs between 2004 and 2009 from a population‐based screening program and ...ascertained death until the end of 2012.
Results
The hazard ratios (HRs) of mortality from OSCC were 1.46 (1.30‐1.65) and 1.18 (1.04‐1.33) in univariable and multivariable analyses, respectively, for treatment delay longer than 6 weeks compared with that shorter than 3 weeks. The corresponding figures were 1.12 (1.01‐1.24) and 1.00 (0.91‐1.11) for treatment delay between 3 and 6 weeks. Advancing age (1.01), higher stage (stage II: 1.84, stage III: 2.97, stage IV: 6.33), cancer in tongue (1.37), or hard palate (1.63) had higher HR of mortality (P < .05). However, treatment at medical center had a lower mortality (0.83, 0.75‐0.91) than local/regional hospital.
Conclusions
Treatment delay longer than 6 weeks for OSCCs detected via a population‐based screening program had unfavorable survival.
Numerous pathogenic
exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion;
) and type 2 (5bp insertion;
) being the most prevalent. Despite the ...universal pathobiology of MPN driven by various
mutants, it is unclear why different
mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in
but not in
MPN-model cells. The expression of
could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting
promoter region in
cells as compared to
cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in
cells. Clinical validation showed significantly enhanced
expression in
-mutated MPN patients compared to
-mutated cases, and thrombocytosis was less prominent in those with
upregulation. This study provides indispensable insights into how different
mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.
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