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: Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. Methods: We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. Results: A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. Conclusion Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Background/Aims: Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. Methods: In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. Results: Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH– (ILPRS in pH+ vs pH–: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH–: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH– subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH– subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). Conclusion Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Human genetic resources are valuable for life science research and pharmaceutical industry.Competitions for human genetic resources and the relevant techniques and industries have increasingly become intense among countries with the the implementation of precision medicine strategy and the maturity of gene editing technology.In the context of scientific progress and efficiency,the Organisation for Economic Co-operation and Development,the most important international economic organization,has proposed solutions to technological development and research paradigm changes from the perspective of national and global public interests.The United States,Japan,the United Kingdom,and some other developed countries have also released their policies and guidelines on the sharing of genetic resource data.In this article we analyzed these policies and guidelines,with an attempt to further improve the administration of human genetic resource sharing in China and promote the legal sharing and effective use of these resources.
China ; Guidelines as Topic ; Human Genetics ; Humans ; Information Dissemination

No abstract available.
Adult ; Hemangioendothelioma ; Humans

BACKGROUND: Progress of lung infection after kidney transplantation is rapid, and the adjustment of immunosuppressive drugs is critical, which related to the prognosis of pneumonia and the maintenance of renal function. Therefore, an accurate diagnosis for the pneumonitis post-kidney transplantation is of great significance for choosing the appropriate treatment scheme. OBJECTIVE: To summarize the diagnosis and treatment of pulmonary infection at different periods after kidney transplantation, and then to explore the proper treatment scheme. METHODS: A retrospective analysis of 178 cases of pulmonary infection at different periods after kidney transplantation was performed. According to the progress of patients with lung inflammation, the lung infection was divided into three phases: early, advanced, and phases, and then given different immunosuppressive treatments combined with glucocorticoids; for those with unclear pathogens, given broad-spectrum antibiotics, antiviral, anti-fungal and other drugs, and targeted anti-infective treatment was underwent once pathogen was confirmed. RESULTS AND CONCLUSION: (1) There were 178 patients with pulmonary infection after kidney transplantation, 90 cases occurred at postoperative 1-6 months (78 cases at postoperative 2-4 months), 16 cases occurred at postoperative 6-12 months, 14 cases occurred at postoperative 12-24 months, 12 cases occurred at postoperative 24-36 months, and 46 cases occurred at postoperative more than 36 months. (2) The clinical symptoms of pulmonary infection at the early stage were not obvious, fever was the earliest or primary symptom, and sometimes it was the only symptom. In some cases, the patients appeared with dry cough, expectoration with white mucous sputum, and the amount of sputum increased if infected with mixed bacteria or fungus. But the pulmonary signs are unobvious, and the main imageology feature of lung tissues showed interstitial inflammation. (3) Totally 173 patients were cured, the recovery rate reached to 97.2% and the curative efficacy was satisfactory. (4) Among five patients who dead from pulmonary infection, three were died from acute respiratory failure, and two were for multiple organ failure. Three patients presented with acute rejection to transplant kidney and were cured, and six patients suffered impaired renal function. (5) These results suggest that there is potential risk for pulmonary infection after renal transplantation and it develops rapidly. Based on the situation of pulmonary infection, the physicians can adjust the dose of immunosuppressor and hormone in time, so as to improve the immunosuppressive state and clarify the pathogen for pulmonary infection, then corresponding treatment for anti-infection will be offered, which is beneficial to increase the recovery rate of pulmonary infection and improve the stability of transplanted renal functions.

OBJECTIVETo investigate the relationship between renal clear cell carcinoma and type 2 diabetes mellitus (DM).

METHODSTwo hundreds and sixty-four patients with renal clear cell carcinoma and four hundred controls who suffered from non-urinary system, non-neoplastic or non-hormone-related disorders, were enrolled from January 2008 to December 2012. The incidence of diabetes between the 2 groups and the relationship between renal clear cell carcinoma and duration of diabetes were compared, moreover, renal clear cell carcinoma patients with DM were compared with patients without DM for their clinical features, laboratory examinations and histological characteristics.

RESULTSThe comparison of renal clear cell carcinoma group and control group: the incidence of DM in the two groups were 19.7% and 12.8% respectively, and the difference was significant (&chi;(2) = 5.86, P < 0.05, OR = 1.68). In the renal clear cell carcinoma group, the proportion of patients with DM diagnosed within 2-4 years was 4.92%, which were significant higher than those in the control group 1.70% (&chi;(2) = 5.49, P < 0.05, OR = 2.91). And men with diabetes had high occurrence risk 86% of renal clear cell carcinoma (OR = 1.86, 95%CI: 1.09-3.15). The comparison of diabetes patients subgroup and non-diabetic patients subgroup in renal clear cell carcinoma group: in respect of clinical features, greatest tumor diameter in the two subgroups were (4.9 ± 2.3) cm and (4.2 ± 2.1) cm respectively, and the difference was significant (t = 1.96, P < 0.05). However, there was no significant difference in terms of age, gender and cancer location between the two subgroups (P > 0.05). In respect of laboratory examinations, serum creatinine in the two subgroups were (72 ± 20) µmol/L and (65 ± 17) µmol/L, and the difference was significant (t = 2.34, P < 0.05); serum urea nitrogen in the 2 subgroups were (7.1 ± 2.1) mmol/L and (6.0 ± 1.5) mmol/L respectively, and the difference was significant too (t = 1.47, P < 0.05). In respect of histological characteristics, the proportion of well differentiated clear cell carcinoma were 80.8% and 81.1% respectively, and the difference was significant (&chi;(2) = 4.23, P < 0.05). The proportion of stage II were 25.0% and 27.8% respectively and the difference was significant (&chi;(2) = 4.08, P < 0.05).

CONCLUSIONSDM is closely related with renal clear cell carcinoma and DM may be a possible risk factor for the tumor. And for elderly patients with diabetes who appear waist discomfort or hematuria, a careful examination of kidney is important to make early diagnosis, give timely treatment and improve survival prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; complications ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Incidence ; Kidney Neoplasms ; complications ; Male ; Middle Aged ; Prognosis

Adult ; Female ; Humans ; Liver Neoplasms ; diagnosis ; surgery ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; surgery ; Sarcoma ; diagnosis ; surgery ; Tomography, X-Ray Computed