Aim
Data on the geoepidemiology and outcomes of primary biliary cholangitis (PBC) in Asia are limited; thus, we aimed to collect and assess this information for Taiwan.
Methods
A nationwide ...population‐based cohort study was undertaken using data from the Taiwan National Health Insurance Research Database. Primary biliary cholangitis was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code 571.6 based on alkaline phosphatase and antimitochondrial antibody measurements and ursodeoxycholic acid treatment.
Results
During 2002–2015, 2737 patients (2137 female patients; mean age, 57.78 years) had PBC. The average annual age‐ and sex‐adjusted prevalence and incidence rates of PBC were 8.092/105 and 1.148/105, respectively. Prevalent cases peaked in patients aged 50–59 years; the female‐to‐male ratio was 4.21. Annual prevalence rates increased with time (average percentage change, 12.03%; p < 0.0001). The annual incidence rates decreased with time (−7.39%; p = 0.000011) in female patients (−8.94%; p = 0.000003) but remained steady in male patients. Female‐to‐male and northern‐to‐southern relative risks of PBC incidence rates ranged from 2.2675 to 4.3318 and from 1.5707 to 3.1725, respectively. The 14‐year hepatocellular carcinoma (HCC) cumulative incidence was 9.11%, and the mortality rate was 32.44%; the cumulative incidences of dyslipidemia, thyroid disease, and extrahepatic cancers were 65.13%, 24.40%, and 12.79%, respectively. Higher cumulative incidences of HCC (p = 0.0064) and mortality (p < 0.0001) were noted in male than female PBC patients; southern Taiwan PBC patients had higher cumulative incidences of mortality (p < 0.0001) than their northern counterparts.
Conclusion
In Taiwan, decreasing trends in incidence rates and the female‐to‐male ratio of PBC patients and specific sex and geographic impacts on the incidence rates and outcomes of PBC demand further investigation.
Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. ...However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan–Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the “A/G” genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 “A/G” genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.
The hepatitis C virus (HCV) genotype-specific impacts on the host metabolic alterations remained inconclusive.
A prospective study including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic ...HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) ≥ 2.5). Paired t-tests were used to compare the pre- and post-treatment variables.
Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR) but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001) and apolipoprotein A1 (p = 0.012) were only found in G2, whereas increased triglyceride/HDL (p = 0.01) ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019) and apolipoprotein A1 (p = 0.012) but a decrease in HOMA-IR (p = 0.04), C-peptide (p = 0.019) and hemoglobin A1c (p = 0.047) were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002) was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01) but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041) and triglyceride (p = 0.044) levels than G2 patients.
G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR.
A comprehensive molecular analysis of the deep-sea blind lobsters of the family Polychelidae, often referred to as "living fossils", is conducted based on all six modern genera and 27 of the 38 ...extant species. Using six genetic markers from both mitochondrial and nuclear genomes, the molecular phylogenetic results differ considerably from previous morphological analyses and reveal the genera Polycheles and Pentacheles to be para- or polyphyletic. As the splitting of Polycheles has strong support from both molecular and morphological data, two new genera, Dianecheles and Neopolycheles, are erected for those species excluded from the clade containing the type species of Polycheles. The pattern of polyphyly of Pentacheles, however, is not robustly resolved, so it is retained as a single genus. Fossil evidence suggests that fossil polychelids inhabited deep-sea environments as early as the Early to Middle Jurassic, demonstrating the enduring adaptation of extant polychelid species to the deep-sea. Time-calibrated phylogeny suggested that modern polychelids probably had an Atlantic origin during the Jurassic period. Since their emergence, this ancient lobster group has continued to diversify, particularly in the West Pacific, and has colonized the abyssal zone, with the deepest genus, Willemoesia, representing the more 'derived' members among extant polychelids. Differences in eye reduction among extant polychelid genera highlight the necessity for ongoing investigations to ascertain the relative degree of functionality of their eyes, if they indeed retain any function.
Objectives
Metabolic syndrome (MetS) and hepatitis C virus (HCV) are associated with a higher risk of impaired pulmonary function (iPF). This study aimed to investigate the relationships among MetS, ...iPF, and viral hepatitis.
Methods
This community-based study enrolled participants undergoing annual health check-ups in southern Taiwan between March and December 2019. We performed multivariable logistic regression analyses adjusted for demographics and characteristics to identify the factors associated with iPF.
Results
A total of 2337 participants completed examinations, of whom 928 (39.7%) had iPF. The participants with iPF were elderly (68.8 ± 12.8 years old) and predominately female (63%). MetS increased the risk of iPF (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.27–1.81, p < 0.001). Beyond age (OR 1.03, 95% CI 1.02–1.04) and smoking (OR 1.309, 95% CI 1.004–1.705), female sex (OR 0.74, 95% CI 0.59–0.93) and high education level (OR 0.96, 95% CI 0.94–0.98, p < 0.001) protected against iPF. HCV was not significantly associated with iPF (OR 1.17, 95% CI 0.90–1.52, p = 0.235) in multivariable analysis. MetS was associated with a higher risk of iPF in the non-HBV/HCV group (OR 1.86, 95% CI 1.54–2.26) and HBV alone group (OR 3.44, 95% CI 1.89–6.28), but not in the HCV alone group (OR 1.02, 95% CI 0.64–1.62).
Discussion
MetS was an independent predictor of iPF, especially the restrictive type, and had different effects in the HBV/non-viral hepatitis and HCV groups. Female sex and education were inversely associated with iPF.
Background
This study aimed to investigate whether maternal allergy is associated with soluble CD14 (sCD14) and fatty acid composition in different stages of lactation and the onset of atopic ...dermatitis (AD) in early childhood.
Methods
In total, 443 mother‐child groups (445 children) were enrolled in the Prediction of Allergies in Taiwanese Children birth cohort study. Colostrum and mature milk at 2 months postpartum (2‐month HM) were collected from lactating mothers. Information regarding parental allergy histories and physician‐diagnosed atopic diseases was obtained using age‐specific questionnaires (0‐2 years). We compared sCD14 levels and the composition of 30 fatty acids in the colostrum and 2‐month HM, respectively, between allergic and non‐allergic mothers and between children with and without AD by the age of 2 years.
Results
In total, 185 (41.8%) mothers presented with allergies, and 154 (34.6%) children had physician‐diagnosed AD by the age of 2 years. Both in the colostrum and 2‐month HM of 289 lactating mothers, sCD14 levels were significantly lower in allergic mothers whose children presented with AD compared with children who did not (P = 0.015 and 0.044, respectively). Among the children with AD who were born to non‐allergic mothers, sCD14 levels were lower. However, the result was not statistically significant (P = 0.376 and 0.264, respectively). Our data revealed the lack of associations between fatty acid composition and AD (P > 0.05).
Conclusion
Decreased sCD14 levels in the colostrum and 2‐month HM were associated with AD at 2 years of age, particularly among children born to mothers with allergies.
Background and Aims: Whether hepatitis C virus (HCV) reactivation occurs and how the viral load evolves in anti-HCV antibody-positive chronic hepatitis B (CHB) patients who underwent nucleos(t)ide ...analogue (Nuc) therapies remain unsolved. Methods: A cohort of 66 such patients was studied. Results: At the start of Nuc treatment (baseline), all patients had detectable hepatitis B virus (HBV) DNA levels (6.05 ± 1.88 log IU/mL), while HCV RNA levels (3.79 ± 1.43 log IU/mL) were detected (i.e., chronic hepatitis C (CHC)) in only 13 patients (19.7%). Following Nuc therapies, HBV DNA levels reached the nadirs at end of therapy (EOT) (6.05 ± 1.88 vs. 0.25 ± 0.99 log IU/mL, p < 0.0001) and relapsed at 6 months after EOT (6mEOT) at a level of 3.45 ± 2.64 log IU/mL compared with EOT (p < 0.0001). Among the 13 CHC patients, a non-significant decrease in HCV RNA was noted at EOT (3.52 ± 1.71 vs. 2.77 ± 2.63 log IU/mL, p = 0.166) but tended to decrease further at 6mEOT (2.77 ± 2.63 vs. 1.89 ± 2.06 log IU/mL, p = 0.063). Two of the thirteen CHC patients showed an increase in HCV-RNA ≥ 1 log10 IU/mL at EOT, and one of the fifty-three patients with undetectable HCV RNA at baseline (i.e., resolved past HCV infection) showed detectable HCV RNA at year 1 (3200 IU/mL) and year 2 (1240 IU/mL) following entecavir therapy. Conclusions: HCV reactivation did occur during HBV suppression, and the rate was 4.5% (3/66), 15.4% (2/13), and 1.9% (1/53), for all patients, CHC patients, and patients with resolved past HCV infection, respectively. The reverse HBV and HCV viral evolutions at 6mEOT indicate that HBV relapse may suppress HCV replication again.
Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It ...might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood.
Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by in vitro incorporation of tritium and for the development of autoimmune thyroiditis or arthritis.
At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG2a in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected in utero. Serum anti-TPO or CII IgG2a persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG2a was enhanced by postnatal TPO or CII challenge.
Fetal exposure to free autoantigens could be immunogenic, shedding new light on the in utero origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus.
There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple ...therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin.
After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion.
A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure.
Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.
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