Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

Objective To develop and validate a deep learning model for automatic identification of liver CT contrast-enhanced phases.Methods A total of 766 patients with liver CT contrast-enhanced images were retrospectively collected.A three-phase classification model and an arterial phase(AP)classification model were developed,so as to automatically identify liver CT contrast-enhanced phases as early arterial phase(EAP)or late arterial phase(LAP),portal venous phase(PVP),and equilibrium phase(EP).In addition,221 patients with liver CT contrast-enhanced images in 5 different hospitals were used for external validation.The annotation results of radiologists were used as a reference standard to evaluate the model performances.Results In the external validation datasets,the accuracy in identifying each enhanced phase reached to 90.50%-99.70%.Conclusion The automatic identification model of liver CT contrast-enhanced phases based on residual network may provide an efficient,objective,and unified image quality control tool.

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.

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.

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.
Humans ; Ischemic Stroke ; Chemokine CXCL12 ; Acupuncture Therapy ; Mesenchymal Stem Cells ; Inflammation

Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4⁺ T cells and CD8⁺ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.

Background/Aims: Cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC), and patients with cirrhosis are recommended to receive semiannual surveillance for early HCC detection. However, early cirrhosis is often asymptomatic and can go undiagnosed for years, leading to underuse of HCC surveillance in clinical practice. We characterized the frequency and associated factors of unrecognized cirrhosis in a national sample of patients with HCC from the United States. Methods: HCC patients aged 68 years and older, diagnosed during 2011 to 2015 were included from the SEERMedicare Linked Database. If cirrhosis was diagnosed within 6 months immediately preceding HCC diagnosis or after HCC diagnosis, cases were categorized as unrecognized cirrhosis. Factors associated with unrecognized cirrhosis were identified using logistic regression analyses. Factors associated with overall survival were evaluated using Cox regression analyses. Results: Among 5,098 HCC patients, 74.8% patients had cirrhosis. Among those with cirrhosis, 57.4% had unrecognized cirrhosis, with the highest proportion (76.3%) among those with NAFLD-related HCC. Male sex (aOR: 2.12, 95% CI: 1.83–2.46), non-Hispanic Black race (aOR: 1.93, 95% CI: 1.45–2.57), and NAFLD etiology (aOR: 4.46, 95% CI: 3.68–5.41) were associated with having unrecognized cirrhosis. Among NAFLD-related HCC patients, male sex (aOR: 2.32, 95% CI: 1.71–3.14) was associated with unrecognized cirrhosis. Unrecognized cirrhosis was independently associated with worse overall survival (aHR: 1.17, 95% CI: 1.08–1.27) compared to recognized cirrhosis. Conclusions Unrecognized cirrhosis is common in NAFLD-related HCC, particularly among male and Black patients, highlighting these groups as important intervention targets to improve HCC surveillance uptake and outcomes.

Objectives: . Type 2 diabetes mellitus (T2DM) is a risk factor for deep neck infection (DNI) and leads to complications and poor outcomes. Our study aimed to investigate the risk, prognosis, and complications of peritonsillar abscess (PTA) in patients with T2DM. Methods: . We extracted data of patients newly diagnosed as having T2DM between January 2000 and December 2011 from Taiwan’s National Health Insurance Research Database. These patients were matched with patients without T2DM, and PTA incidence was compared between both cohorts. Results: . In total, 67,852 patients with and 135,704 patients without T2DM were enrolled. PTA incidence was significantly higher in patients with T2DM (incidence rate ratio, 1.91; P<0.001); moreover, PTA incidence was higher at 1 to 5 years after T2DM diagnosis than at <1 and >5 years after T2DM diagnosis. Cox regression analysis showed that patients with T2DM had an approximately 2-fold higher PTA risk (adjusted hazard ratio [aHR]: 1.89, P<0.001). Patients with a higher adapted Diabetes Complications Severity Index (aDCSI) had higher PTA risk than those with a lower aDCSI (aHRs: 2.17 for aDCSI ≥1, P=0.006 and 1.81 for aDCSI=0, P=0.002). T2DM patients with a high aDCSI (≥1) had a nonsignificantly longer hospitalization duration and a higher rate of DNI complications than did those with a low aDCSI (=0). Conclusion . In patients with T2DM, PTA incidence was relatively high, and it increased with T2DM severity. Moreover, T2DM patients should be particularly careful about PTA within 1 to 5 years after the diagnosis, and physicians should keep in mind that the prognosis of PTA was correlated with T2DM severity.