Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Exotoxins produced by Actinobacillus (A.) pleuropneumoniae (Apx) play major roles in the pathogenesis of pleuropneumonia in swine. This study investigated the role of ApxI in hemolysis and cellular damage using a novel apxIA mutant, ApxIA336, which was developed from the parental strain A. pleuropneumoniae serotype 10 that produces only ApxI in vitro. The genotype of ApxIA336 was confirmed by PCR, Southern blotting, and gene sequencing. Exotoxin preparation derived from ApxIA336 was analyzed for its bioactivity towards porcine erythrocytes and alveolar macrophages. Analysis results indicated that ApxIA336 contained a kanamycin-resistant cassette inserted immediately after 1005 bp of the apxIA gene. Phenotype analysis of ApxIA336 revealed no difference in the growth rate as compared to the parental strain. Meanwhile, ApxI production was abolished in the bacterial culture supernatant, i.e. exotoxin preparation. The inability of ApxIA336 to produce ApxI corresponded to the loss of hemolytic and cytotoxic bioactivity in exotoxin preparation, as demonstrated by hemolysis, lactate dehydrogenase release, mitochondrial activity, and apoptosis assays. Additionally, the virulence of ApxIA336 appeared to be attenuated by 15-fold in BALB/c mice. Collectively, ApxI, but not other components in the exotoxin preparation of A. pleuropneumoniae serotype 10, was responsible for the hemolytic and cytotoxic effects on porcine erythrocytes and alveolar macrophages.
Actinobacillus pleuropneumoniae/genetics/*pathogenicity/*physiology ; Animals ; *Apoptosis ; Bacterial Proteins/genetics/metabolism ; Blotting, Southern ; Exotoxins/*genetics ; Hemolysin Proteins/genetics/metabolism ; *Hemolysis ; Macrophages, Alveolar/metabolism/*microbiology ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Swine ; Virulence

Symptomatic gastro-intestinal metastasis in lung cancer is extremely rare and only a few case reports have been published. Here, we report a case with lung adenocarcinoma that presented with acute abdominal pain, nausea and vomiting due to duodenum, jejunum, and colon obstruction by the gastro-intestinal metastasis. The patient underwent colonoscopy and the pathologic report was adenocarcinoma. When there are similar histologic findings in both colon and pulmonary lesion, the question is whether both lesions are primary cancer or the colon lesions are metastases from lung cancer. Microscopic examination of a conventional pathologic section was not sufficient to make this determination. Immunohistochemistry was positive for thyroid transcription factor-1 (TTF-1) and cytokeratin 7 (CK7), and negative for cytokeratin 20 (CK20) and caudal-related homeobox transcription factor-2 (CDX-2) on colon mucosa specimen. Accordingly, we used immunohistochemical marker for differential diagnosis of primary adenocarcinoma of the lung with gastro-intestinal metastasis.
*Abdominal Pain ; Adenocarcinoma/*diagnosis/pathology ; Colonoscopy ; Diagnosis, Differential ; Gastrointestinal Neoplasms/*pathology/secondary ; Homeodomain Proteins/metabolism ; Humans ; Immunohistochemistry ; Keratin-20/metabolism ; Keratin-7/metabolism ; Lung Neoplasms/*diagnosis/pathology ; Male ; Middle Aged ; Nuclear Proteins/metabolism ; Tomography, X-Ray Computed ; Transcription Factors/metabolism

BACKGROUND/AIMS: The aim of the study was to evaluate the efficacy of i-scans for the diagnosis of gastroesophageal reflux disease, especially where only minimal change is involved. METHODS: The esophageal mucosa was inspected using an i-scan following conventional white light endoscopy. The examination with iscan was performed under tone enhancement (TE) esophagus (e) mode. Patients with subtle distal esophageal mucosal changes without definite mucosal breaks, such as blurring of Z-line (B), mucosal coarseness (C), hyperemic or purplish discoloration (D), erythema (E), ectopic gastric mucosal islet (I) and mixed type were classified as minimal change. RESULTS: A total of 156 patients were included. Using i-scan endoscopy, the number of minimal change was found to further increase from 94 (conventional endoscopy; 19B, 9C, 29D, 13E, 5I, 19 mixed type) to 109 (i-scan; 15B, 8C, 29D, 16E, 5I, 36 mixed type). And 14 patients who had single type by conventional endoscopy were converted to mixed type after i-scan. Therefore, 29 of 156 patients were upgraded after i-scan, they were account for 19% (p<0.0001; 95% confidence interval, 0.13 to 0.25). CONCLUSIONS: The use of i-scan endoscopy significantly improves the identification of minimal change and helps to identify more precisely the type of minimal change.
Endoscopy ; Erythema ; Esophagus ; Gastroesophageal Reflux ; Humans ; Light ; Mucous Membrane

BACKGROUND/AIMS: The aim of the study was to evaluate the efficacy of i-scans for the diagnosis of gastroesophageal reflux disease, especially where only minimal change is involved. METHODS: The esophageal mucosa was inspected using an i-scan following conventional white light endoscopy. The examination with iscan was performed under tone enhancement (TE) esophagus (e) mode. Patients with subtle distal esophageal mucosal changes without definite mucosal breaks, such as blurring of Z-line (B), mucosal coarseness (C), hyperemic or purplish discoloration (D), erythema (E), ectopic gastric mucosal islet (I) and mixed type were classified as minimal change. RESULTS: A total of 156 patients were included. Using i-scan endoscopy, the number of minimal change was found to further increase from 94 (conventional endoscopy; 19B, 9C, 29D, 13E, 5I, 19 mixed type) to 109 (i-scan; 15B, 8C, 29D, 16E, 5I, 36 mixed type). And 14 patients who had single type by conventional endoscopy were converted to mixed type after i-scan. Therefore, 29 of 156 patients were upgraded after i-scan, they were account for 19% (p<0.0001; 95% confidence interval, 0.13 to 0.25). CONCLUSIONS: The use of i-scan endoscopy significantly improves the identification of minimal change and helps to identify more precisely the type of minimal change.
Endoscopy ; Erythema ; Esophagus ; Gastroesophageal Reflux ; Humans ; Light ; Mucous Membrane

PURPOSE: The patients with metastatic breast cancer are routinely exposed to taxane and anthracycline as neoadjuvant, adjuvant, and palliative chemotherapeutic agents. This study was designed to evaluate the efficacy and safety of using a vinorelbine and ifosfamide (VI) combination treatment in patients with taxane-resistant metastatic breast cancer. METHODS: We evaluated the use of a VI regimen (25 mg/m2 vinorelbine administered on days 1 and 8 plus 2,000 mg/m2 ifosfamide administered on day 1-3 every 3 weeks) for breast cancer patients who evidenced tumor progression after palliative taxane treatment. RESULTS: Overall, 35 patients were enrolled in this study: Their median age was 50 years (range, 38-72 years). The overall response rate was 40.0% (14 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 4.5 months (95% CI, 3.5-5.4 months). The median overall survival was 18.3 months (95% CI, 12.9-23.6 months). In the 190 cycle of treatment, the incidence of grade > or =3 neutropenia, anemia, and thrombocytopenia was 29.3%, 4.2%, and 2.0%, respectively. Neutropenic fever was noted in 6 cycles (3.1%). The non-hematological toxicities were not severe: grade 1 or 2 vomiting was observed in 22.8% of the patients. CONCLUSION: Our results suggest that the use of vinorelbine and ifosfamide (VI) combination chemotherapy appears to be effective and it showed an acceptable toxicity profile in the patients with taxane-resistant metastatic breast cancer.
Anemia ; Breast ; Breast Neoplasms ; Bridged Compounds ; Drug Therapy, Combination ; Fever ; Humans ; Ifosfamide ; Incidence ; Neutropenia ; Taxoids ; Thrombocytopenia ; Vinblastine ; Vomiting

Serum CA 125 is the most useful marker for monitoring patients with epithelial ovarian cancer. However, it can be elevated above normal level in a variety of conditions other than ovarian cancer such as endometriosis, pelvic inflammation disease, and other malignant or nonmalignant disorders, including pulmonary diseases. Recently, we experienced a case of bronchiectasis in which the serum CA 125 level was elevated, changing with the patient's condition. There was no evidence of underlying malignant disease on positron emission tomography or on gynecologic examination, including transvaginal ultrasonography. During follow-up for 14 months, we could not find any clue of malignant disease that could have been the cause of the elevated levels of serum CA 125. Elevated serum CA 125 level should be interpreted carefully according to the patient's clinical condition. In addition, our case suggests that CA 125 may be used as a surrogate marker for acute inflammatory status for chronic pulmonary diseases.
Biomarkers ; Bronchiectasis ; CA-125 Antigen ; Endometriosis ; Female ; Follow-Up Studies ; Humans ; Inflammation ; Lung Diseases ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Positron-Emission Tomography

The objectives of this cohort analysis were to explore the relationship between insulin resistance (IR) and the criteria for metabolic syndrome (MetS) and to evaluate the ability to detect IR in subjects fulfilling those criteria. We enrolled 511 healthy subjects (218 men and 283 women) and measured their blood pressure (BP), body mass index, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting plasma glucose levels. Insulin suppression testing was done to measure insulin sensitivity as the steady-state plasma glucose (SSPG) value. Subjects with an SSPG value within the top 25% were considered to have IR. The commonest abnormality was a low HDL-C level, followed by high BP. The sensitivity to detect IR in subjects with MetS was about 47%, with a positive predictive value of about 64.8%, which has higher in men than in women. In general, the addition of components to the criteria for MetS increased the predictive value for IR. The most common combination of components in subjects with MetS and IR were obesity, high BP, and low HDL-C levels. All of the components were positive except for HDL-C, which was negatively correlated with SSPG. The correlation was strongest for obesity, followed by high TG values. In subjects with MetS, sensitivity for IR was low. However, body mass index and TG values were associated with IR and may be important markers for IR in subjects with MetS.
Adult ; Aged ; *Biological Markers ; Blood Glucose/metabolism ; Blood Pressure ; Body Mass Index ; Cholesterol, HDL/blood ; Female ; Humans ; *Insulin Resistance ; Male ; Metabolic Syndrome X/*diagnosis/*epidemiology ; Middle Aged ; Obesity, Morbid/diagnosis/epidemiology ; Predictive Value of Tests ; Prevalence ; Risk Factors ; Sensitivity and Specificity ; Triglycerides/blood