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: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. Methods: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. Results: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. Conclusion Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI’s pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2·insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

To explore the effect of tanshinone IIA (TanIIA) on the occurrence and development of breast cancer, we employed the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice as a spontaneous breast cancer mouse model. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. The animals were divided into control group, low-dose TanIIA treatment group (30 mg·kg^-1·day^-1), and high-dose TanIIA treatment group (60 mg·kg^-1·day^-1). The treatment was administered orally and daily for 5 weeks. The mice were sacrificed after final treatment. Mammary gland and lung were collected for histopathology studies. We evaluated the chemoprophylaxis effect of TanIIA on breast cancer in mice according to the pathological characteristics of breast cancer at different stages of development. Immunofluorescence staining were employed for blood vessel analysis. The expression levels of E-cadherin, proliferating nuclear antigen (PCNA), and oncogene c-Myc were detected by immunohistochemistry. Flow cytometry was used to analyze cell cycle and Cytoscape was used to construct drug-disease protein-protein interaction (PPI) network. Our results showed that TanIIA inhibits breast tumor progression by delaying malignancy from adenoma to early carcinoma, and inhibits blood vessel formation during tumor development. TanIIA (60 mg·kg^-1·day^-1) inhibits the expression levels of PCNA and c-Myc, upregulates the expression of E-cadherin. In addition, cell cycle experiments showed that the cell cycle of PyMT primary mammary cells in the high-dose TanIIA group was arrested in the G0/G1 phase. Our study demonstrated that TanIIA can significantly inhibit breast tumor progression in MMTV-PyMT mouse model, which may be related to the inhibition of angiogenic switch and cell cycle arrest.

Objective:To investigate the clinical efficacy of perihilar surgical techniques for diffuse hepatolithiasis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 122 patients with diffuse hepatolithiasis who were admitted to Hunan Provincial People's Hospital from January 2010 to December 2015 were collected. There were 39 males and 83 females, aged from 21 to 82 years, with a median age of 51 years. After perihilar hepatectomy, the first, second and third divisions of hepatic ducts were opened longitudinally. Strictures in the bile ducts were relieved by stricturoplasty and internal bile duct anastomosis, and stones were removed by multiple methods under direct vision. After resection of severe atrophic liver segment along the plane of hepatic atrophy or bile duct stricture, T-tube or hepaticojejunos-tomy was used for internal drainage. Observation indicators: (1) surgical situations; (2) stricture relief and stone removal. (3) Follow-up. Follow-up was conducted by Wechat, telephone interview or outpatient examination. Patients were followed up once every 3 months in the postoperative 1 year through liver function and abdominal B-ultrasound examination. Subsequently, liver function and abdominal B-ultrasound were reexamined once a year. Magnetic resonance cholangiopancreato-graphy and computed tomography were performed when cholangitis or stone recurrence was suspected to analyze stone recurrence and patient survival. The follow-up was up to July 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical situations: for the 122 patients, the operation time, hepatic portal occlusion time, volume of intraoperative blood loss, duration of postoperative hospital stay were (253±71)minutes, 15 minutes(range, 14?38 minutes), 200 mL(range, 100?1 100 mL), (12±5)days. Postoperative complications occurred to 40 of 122 patients. There were 9 cases of incision infection, 8 cases of bile leakage (5 cases of bile leakage at hepatic section, 3 cases of choledochojejunostomy leakage), 8 cases of septicemia, 7 cases of pleural effusion, 5 cases of abdominal abscess, 3 cases of liver failure, 1 case of biliary bleeding. Some patients had multiple complications. Among the 122 patients, 2 cases died after operation, including 1 case of postoperative liver failure and 1 case of disseminated intravascular coagulation caused by biliary-intestinal anastomotic leakage complicated with sepsis. Patients with bile leakage and abdominal abscess were improved after puncture and drainage under the guidance of B-ultrasound. Patients with cholangiojejunal anastomotic bleeding were embolized through the right hepatic artery. The other complications were improved after conservative treatment. (2) Stricture relief and stone removal: 85 of 88 patients with biliary stricture were relieved, with the stricture relief rate of 96.59%(85/88). Among the 122 patients, 103 cases had stones completely removed and 19 cases had residual stones. The immediate stone clearance rate was 84.43%(103/122). Of the 19 patients with residual stones, choledochoscopy was refused in 3 cases and choledochoscope lithotripsy was performed in 16 cases, of which 7 cases were removed and 9 cases were still residual stones. Of the 122 patients, 110 cases were finally removed stones, 12 cases were eventually residual stones, and the final stone clearance rate was 90.16%(110/122). (3) Follow-up: among the 122 patients, 120 cases including 110 cases with find stone removal and 10 cases with residual stones were followed up for (78±14)months. The 1-, 3, 5-year stone recurrence rates of 120 patients were 0.83%(1/120), 6.67%(8/120), 9.17%(11/120), respectively. The 1-, 3-, 5-year stone recurrence rates of 110 patients with final stone removal were 0, 5.45%(6/110), 5.45%(6/110), respectively. The number of cases with stone recurrence at postoperative 1-, 3- and 5-year of 10 patients with residual stones were 1, 2, 5 cases, respectively. Of 120 patients with follow-up, 1 case died of end-stage liver disease, and the other patients had good survival.Conclusion:Perihilar surgical techniques for diffuse hepatolithiasis is safe and effective.

Objective:To explore the value of " internal anastomosis" of bile duct , ie intrahepatic duct stricture resection, cholangioplasty and bilioenteric anastomasis, in the treatment of hepatolithiasis with stricture of bile duct orifice.Methods:The clinical data of 74 patients undergoing this procedure from Dec 2017 to Dec 2019 at Hu′nan Provincial Peopole′s Hospital were retrospectively analysed.Results:All 74 patients received intraoperative choledochoscopy lithotomy, and 26 cases had a hepatectomy for atrophic fibrosis. There were 27 cases with orifice stricture of left-lateral bile duct or its major branchs; 22 cases with that of caudate lobe ducts. 3 cases with that of right anterior ducts; 8 cases with that of right posterior bileduct; and 14 cases with that of bilateral multiple bile ducts . The average operation time was (243±31) min (ranging from 180 to 360 min), the average intraoperative blood loss was (150±26) ml (ranging from 100 to 600 ml). The average postoperative hospital stay was (10.0±2.2) d. The occurrence rate of residual stone was 8.1%. 14 cases (18.9%) had postoperative complications , including 2 cases with bleeding, 1 case with bile leakage, 4 cases with wound infection, 13 cases with pleural effusion. All were cured by conservative therapy, and no complications of grading Ⅲa or above happened according to Clavien Dindo grading system. All 74 cases were followed up, the average follow-up time was (10.2±3.6) months (ranging from 6 to 18months) with good result.Conclusion:" internal anastomosis" is an effective method to remove the narrow openings of intrahepatic bile ducts , thus helps to preserve much possible liver parenchyma, while decreasing the rate of residual stone.

Objective To explore the value of round ligament approach in the bile duct benign stricture near porta hepatis.Methods Data of 62 patients treated in Hunan Provincial People's Hospital from Mar 2016 to Mar 2018 were retrospectively analyzed.Results Hepatolithiasis was the cause of bile duct benign stricture in 37 cases,followed by iatrogenic injury (12 cases),cholangio-intestinal anastomotic restenosis (7 cases),cystic dilatation of bile duct (4 cases) and bridge-shaped calculus (2 cases).We get access to the strictured bile duct near porta hepatis by way of round ligament,and hilar cholangioplasty and bilioenteric anastomosis was done at the porta hepatis.The surgery lasted an average of 230.3 minutes and with an average 196.8 ml blood loss.By Clavien-Dindo scoring system,there were Grade Ⅰ complications in 32 cases,Grade Ⅱ complications in 3.On follow-up survey,there were 3 patients with reflux cholangitis.Condclsion Round ligament is a gateway to hilar bile duct benign stricture in an attempt to make hilar cholangioplasty.