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: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients.
Aging ; Awards and Prizes ; Delivery of Health Care ; Education ; Financing, Organized ; Humans ; Mentors ; Osteoporosis ; Practice Guidelines as Topic ; Taiwan

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

OBJECTIVETo observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies.

METHODSA double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8.

RESULTSAt week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride.

CONCLUSIONThe combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.

Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.
Dendritic Cells/immunology ; Female ; Genetic Vectors ; Humans ; *Immunotherapy ; Papillomavirus Infections/*complications/therapy ; Papillomavirus Vaccines/therapeutic use ; *Translational Medical Research ; Uterine Cervical Neoplasms/*therapy ; Vaccines, DNA/therapeutic use ; Vaccines, Subunit/therapeutic use

OBJECTIVES: To compare the short- and long-term hearing outcomes after successful inlay cartilage tympanoplasty between patients with small (< or =25%) and large (> or =50%) eardrums perforations. METHODS: This is a retrospective case series study conducted in a tertiary referral center. Twenty-five patients who underwent 27 procedures were enrolled. Their mean age was 60.26 years (range, 42 to 76 years). The mean follow-up time was 18.86 months (range, 12.30 to 35.83 months). The preoperative, initial postoperative, and long-term hearing results in patients with total repair of the eardrum were analyzed. RESULTS: In the small size group, the average (+/-standard deviation) air-bone gap (ABG) closure was 1.08+/-7.53 dB in the short-term and 2.33+/-11.56 dB in the long-term hearing examinations. There was no difference between short- and long-term ABG closure (P=0.689). In the large size group, the average ABG closure was 9.77+/-9.40 dB in the short-term and 16.25+/-6.01 dB in the long-term hearing examinations. There was a significant difference between short- and long-term ABG closure (P=0.029). CONCLUSION: Patients with large perforations have continuous hearing improvement and ABG closure for more than one year. In contrast, the short- and long-term postoperative ABGs are almost the same in patients with small perforations. More long-term postoperative follow-up of hearing results is necessary for large perforations.
Cartilage* ; Follow-Up Studies ; Hearing* ; Humans ; Inlays* ; Retrospective Studies ; Tertiary Care Centers ; Tympanic Membrane* ; Tympanoplasty*

INTRODUCTIONCardiopulmonary resuscitation (CPR) guidelines were revised in 2005 based on new evidence and expert consensus. However, the benefits of the new guidelines remain undetermined and their influence has not been published in Asia. This study aimed to evaluate the impact of implementing the new resuscitation guidelines and identify factors that influence the discharge survival of out-of-hospital cardiac arrest (OHCA) patients in an Asian metropolitan city.

MATERIALS AND METHODSThis was an observational cohort study of all OHCA patients seen by the emergency medical service during the period before (Nov 2003 to Oct 2005) and after (May 2006 to Oct 2008) implementing the new resuscitation guidelines. Detailed clinical information was recorded using the Ustein style template. Statistical analysis was done using X2 test or t-test for univariate analysis and the logistic regression model for multivariate analysis.

RESULTSThere were 463 patients before and 430 patients after the new guidelines who received resuscitation. The rate of recovery of spontaneous circulation (ROSC), survival-to-intensive care unit (ICU) admission, and survival-to-hospital discharge all showed no benefits regarding the new resuscitation guidelines (ROSC: 42% vs 39%, P = 0.32; Survival-to-ICU admission: 33% vs 30%, P = 0.27; survival-to-hospital discharge: 10% vs 7%, P = 0.09). The rate of ventricular fibrillation/pulseless ventricular tachycardia (VF/pulseless VT), rate of witnessed arrest, and rate of bystander CPR were much lower than in Western studies. After multivariate logistic regression, factors related to discharge survival were witnessed arrest and initial rhythm with VF/pulseless VT. The new resuscitation guidelines did not significantly influence the discharge survival.

CONCLUSIONSWe did not observe any improvement in survival after implementing the new guidelines. Independent factors of survival-to-hospital discharge are witnessed arrest and initial rhythm with VF/pulseless VT. Because the rates of VF/pulseless VT and bystander CPR in Asia are low, popularising CPR training programmes and increasing the rate of bystander CPR may be more important for improving OHCA survival rates than frequent guideline changes.

Aged ; Aged, 80 and over ; Cardiopulmonary Resuscitation ; methods ; standards ; Emergency Service, Hospital ; statistics & numerical data ; Female ; Hospitals, University ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Out-of-Hospital Cardiac Arrest ; mortality ; therapy ; Patient Discharge ; statistics & numerical data ; Practice Guidelines as Topic ; Survival Analysis ; Taiwan ; epidemiology

BACKGROUNDPost-operation pain is a very subjective phenomenon. The aim of this study was to find out the effects of acupuncture or electro-acupuncture on post-cesarean pain.

METHODSSixty women, who had had spinal anesthesia during cesarean section at the Department of Obstetrics of China Medical University Hospital, were randomly assigned to the control group, the acupuncture group, and the electro-acupuncture group. After the operation, we applied subjects with acupuncture or electro-acupuncture on the bilateral acupuncture point, San Yin Jiao (Sp6), and the patient controlled analgesia (PCA). The first time of requesting morphine, the frequency of PCA demands in 24 hours, and the doses of PCA used were recorded double blindly. In addition, monitoring the subjects' vital signs, the opioid-related side effects, and the pain scores was done.

RESULTSThe results showed that the acupuncture group and the electro-acupuncture group could delay the time of requesting morphine up to 10 - 11 minutes when compared with the control group. The total dose of PCA used within the first 24 hours was 30% - 35% less in the acupuncture group and the electro-acupuncture group when compared with the control group, which was indicated in statistical significance. However, there was no significant difference between the acupuncture group and the electro-acupuncture group. The electro-acupuncture group's and the acupuncture group's pain scores were lower than the control group's within the first 2 hours. Both were statistically significant. However, two hours later, there were no significant differences of the visual analogue scale (VAS) scores between either of the treatment groups and the control group. Finally, the incidence of opioid-related side effects, such as dizziness, was less in the acupuncture group and electro-acupuncture group than in the control group.

CONCLUSIONSThis study shows that the application of acupuncture and electro-acupuncture could definitely delay the time of requesting pain relief medication after cesarean section and decrease the PCA doses used within the first 24 hours.

Acupuncture Therapy ; methods ; Adult ; Analgesics ; therapeutic use ; Cesarean Section ; Female ; Humans ; Male ; Morphine ; therapeutic use ; Pain, Postoperative ; drug therapy ; therapy ; Pregnancy

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