CAMP-B score predicts the risk of hepatocellular carcinoma in patients with chronic hepatitis B after HBsAg seroclearance.

BACKGROUND: Risk of hepatocellular carcinoma (HCC) persists after hepatitis B surface antigen (HBsAg) seroclearance in patients with chronic hepatitis B (CHB). AIMS: To identify risk factors and construct a predictive model for HCC development. METHODS: We retrospectively analysed patients with CHB with HBsAg seroclearance. Primary outcome was HCC development. Factors identified from a multivariate Cox model in the training cohort, consisting of 3476 patients from two Korean hospitals, were used to construct the prediction model. External validation was performed using data from 5255 patients in Hong Kong. RESULTS: In the training cohort, HCC occurred in 102 patients during 24,019 person-years of observation (0.43%/year). Risk scores were assigned to cirrhosis (C:3), age ≥50 years (A:2), male sex (M:3) and platelet count <150,000/mm3 (P:1); all were independently associated with an increased risk of HCC in multivariate analysis The time-dependent area under receiver operating characteristic curves for 5, 10 and 15 years in the training and validation cohorts were 0.782, 0.817 and 0.825 and 0.785, 0.771 and 0.796, respectively. In the validation cohort, 85 patients developed HCC (0.24%/year). The corresponding incidence of HCC in the low-, intermediate- and high-risk groups were 0.07%, 0.37% and 0.90%, respectively. CONCLUSIONS: The CAMP-B score (cirrhosis, age ≥50 years, male sex and platelet count <150,000/mm3/L) was significantly associated with HCC development after HBsAg seroclearance. CAMP-B score can be easily implemented in real-world clinical practice and helps stratify HCC risk in patients with CHB following HBsAg seroclearance.

Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

The associations between fibrosis changes and liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with liver fibrosis. We investigated the associations between changes in liver stiffness measurement (LSM) over 3-year period and the development of cirrhosis or hepatocellular carcinoma (HCC) in patients with MASLD. METHODS: This study involved patients with MASLD who underwent transient elastography at baseline and 3 years after baseline from 2012 to 2020. Low (L), indeterminate (I) and high (H) LSM values were classified as <8 kPa, 8-12 kPa and >12 kPa respectively. RESULTS: Among 1738 patients, 150 (8.6%) were diagnosed with cirrhosis or HCC. The proportions of patients with L, I and H risk were 69.7%, 19.9% and 10.5% at baseline, and 78.8%, 12.8% and 8.4% at 3 years after baseline, respectively. The incidence rates of cirrhosis or HCC per 1000 person-years were 3.7 (95% confidence interval [CI], 2.4-5.5) in the L → L + I group, 23.9 (95% CI, 17.1-32.6) in the I → L + I group, 38.3 (95% CI, 22.3-61.3) in the H → L + I group, 62.5 (95% CI, 32.3-109.2) in the I → H group, 67.8 (95% CI, 18.5-173.6) in the L → H group and 93.9 (95% CI 70.1-123.1) in the H → H group. Two risk factors for the development of cirrhosis or HCC were LSM changes and low platelet counts. CONCLUSION: LSM changes could predict clinical outcomes in patients with MASLD. Thus, it is important to monitor changes in the fibrotic burden by regular assessment of LSM values.

A Comparison of Health Risks from PM2.5 and Heavy Metal Exposure in Industrial Complexes in Dangjin and Yeosu·Gwangyang.

Particulate matter (PM) can cause illness, including respiratory diseases, and PM2.5 compositions are likely to vary according to the emission profiles of industrial complexes. This study analyzed and compared the concentrations and distributions of PM2.5 and heavy metals in two regions of Republic of Korea: Yeosu·Gwangyang, which houses a massive national industrial complex, and Dangjin, which houses power plants. Further, we conducted a health risk assessment on the residents of the areas near these industrial complexes. Measurements were taken at five different points in each setting over a two-year period from August 2020 to August 2022. We found differences in PM2.5 concentrations and heavy metal composition ratios across the sites. Specifically, PM2.5 concentrations exceeded the standard of 1 at all measurement sites, while the specific heavy metals exceeding the standard varied across the sites. Ultimately, we observed regional differences in PM2.5 composition across measurement sites across and within the two regions and variations in health risks and according health effects due to the absence of PM2.5 toxicity values, and compared the health risks of two industrial complexes with different characteristics. These findings underscore the importance of considering not only PM2.5 but also its composition in exposure and health risk assessments.

Hepatitis C virus infection in patients undergoing surgery in a single tertiary academic center.

BACKGROUND AND AIM: Lack of awareness disturbs proper care for hepatitis C virus (HCV) infections in patients undergoing surgery. We investigated the status of HCV screening, confirmation, and treatment in patients who underwent surgery. METHODS: Patients who underwent surgery at a tertiary academic center between 2019 and 2021 were eligible for this retrospective study. RESULTS: Between 2019 and 2021, 96 894 patients (40 121 males; 41.4%) who underwent surgery under general anesthesia were recruited. The median age of the participants was 55.0 years. Of the 83 920 (86.6%) patients who tested positive for anti-HCV antibodies, 576 (0.7%) showed positive results, with a higher proportion of patients with diabetes mellitus (32.6% vs 18.5%), hypertension (50.5% vs 28.6%), liver cirrhosis (13.2% vs 1.7%), and unfavorable laboratory test results when compared with those with negative results (all P < 0.05). HCV RNA was tested in 215 patients (37.3%), with a positivity rate of 20.5% (n = 44). Of the 44 patients, 42 (95.5%) were referred for antiviral treatment, and 29 (69.0%) were successfully treated with direct-acting antiviral therapy. HCV RNA confirmation rates were higher in the Department of Hepatobiliary and Transplant Surgery (76.6%) than in the other surgical departments (25.0-33.5%) (P < 0.001). CONCLUSIONS: The proportion of patients who were positive for anti-HCV antibodies and failed to receive proper management after surgery was not negligible. Increased awareness of HCV infection among surgeons through appropriate education may be required.

Mobile App-Based Lifestyle Coaching Intervention for Patients With Nonalcoholic Fatty Liver Disease: Randomized Controlled Trial.

BACKGROUND: Lifestyle modification in patients with nonalcoholic fatty liver disease (NAFLD) is key to improving health outcomes. Mobile health technologies may offer potential effective and efficient health care support to facilitate self-management. OBJECTIVE: This study aims to develop a lifestyle coaching intervention using a mobile app for patients with NAFLD and evaluate physiological and psychological health outcomes for 6 months. METHODS: This study was a randomized controlled trial. The personalized lifestyle coaching intervention using a mobile app was developed through established guidelines and literature reviews. This intervention consisted of information on NAFLD management, diet and physical activity self-monitoring, and coaching sessions based on patient records and SMS text messages. A total of 102 individuals were enrolled in the study and randomly assigned to the intervention group (n=48) or the control group (n=54). The outcomes were improvements in physiological (weight, liver fat score, aspartate aminotransferase, alanine transferase, and gamma-glutamyl transferase) and clinical outcomes (self-management, NAFLD self-management knowledge, self-efficacy, fatigue, depression, and quality of life). Data were analyzed using descriptive analysis and a linear mixed model to test the effects of the intervention. RESULTS: All participants completed the study. The mean age of the participants was 48.9 (SD 13.74) years, 38.2% (39/102) were female participants, and 65.7% (67/102) were married. There were no differences in baseline demographic and clinical data between the intervention and control groups. Changes from baseline to 6 months were significant only within the intervention group for weight (P<.001), liver fat score (P=.01), aspartate aminotransferase (P=.03), alanine transferase (P=.002), gamma-glutamyl transferase (P=.04), self-management (P<.001), fatigue (P=.005), depression (P=.003), and quality of life (P<.001). The differences between the 2 groups for the changes over the 6 months were significant in self-management (P=.004), self-management knowledge (P=.04), fatigue (P=.004), depression (P=.04), and quality of life (P=.01). However, the intervention-by-time interaction was significantly effective only for self-management (P=.006) and fatigue (P=.02). CONCLUSIONS: Nonpharmacological interventions using a mobile app may be effective in improving the physiological and psychological health outcomes of patients with NAFLD. TRIAL REGISTRATION: Clinical Research Information Service KCT0005549; http://tinyurl.com/y2zb6usy.

The effect of sham acupuncture can differ depending on the points needled in knee osteoarthritis: A systematic review and network meta-analysis.

Objective: In sham acupuncture-controlled acupuncture clinical trials, although sham acupuncture techniques are different from those of verum acupuncture, the same acupuncture points are often used for verum and sham acupuncture, raising the question of whether sham acupuncture is an appropriate placebo. We aimed to examine the effects of sham and verum acupuncture according to the points needled (same or different between verum and sham acupuncture) in knee osteoarthritis. Methods: Ten databases were searched to find randomized controlled clinical trials (RCTs) assessing the effects of verum acupuncture with sham acupuncture or waiting lists on knee osteoarthritis. Sham acupuncture was classified as using the same acupuncture points as those in verum acupuncture (SATV) or using sham points (SATS). A frequentist network meta-analysis (NMA) was conducted, and the certainty of evidence was evaluated. Results: A total of 10 RCTs involving 1628 participants were included. Verum acupuncture was significantly superior to SATS but not different from SATV in terms of pain reduction. Additionally, SATV was significantly superior to the waiting list. For physical function, no difference were found between verum acupuncture, SATV, and SATS. The certainty of evidence was low to moderate. Conclusion: For knee osteoarthritis, the pain reduction effect of acupuncture may differ according to the needling points of sham acupuncture, and the control group should be established according to the specific aim of the study design and treatment mechanism.

Neither hepatic steatosis nor fibrosis is associated with clinical outcomes in patients with intestinal Behçet's disease.

BACKGROUND: Behçet's disease (BD) and nonalcoholic fatty liver disease (NAFLD) are chronic inflammatory diseases that share pathogenetic mechanisms. In this study, we investigated whether NAFLD influences the clinical outcomes in patients with intestinal BD. METHODS: Patients with intestinal BD and available hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) scores were recruited between 2005 and 2022. An HSI of ≥30 and FIB-4 of ≥1.45 were used to diagnose hepatic steatosis and significant liver fibrosis, respectively. The primary outcomes were intestinal BD-related hospitalization, surgery, emergency room visits, or the first use of corticosteroids, immunomodulators, or biologic agents for intestinal BD. RESULTS: A total of 780 patients with BD were selected. The prevalence of hepatic steatosis and significant liver fibrosis were 72.3% and 8.8%, respectively. Multivariate analysis showed that younger age, prior smoking history, concomitant skin lesions, higher white blood cell count, and lower serum albumin levels were independently associated with an increased risk of clinical relapse (all P < 0.05), whereas hepatic steatosis and significant liver fibrosis were not (hazard ratio [HR] = 1.164, 95% confidence interval [CI] 0.923-1.468; P = 0.199 for hepatic steatosis; HR = 0.982, 95% CI 0.672-1.436; P = 0.927 for significant liver fibrosis). CONCLUSION: Hepatic steatosis and liver fibrotic burden were not independently associated with clinical outcomes in patients with intestinal BD.

Analysis of progression after elective distal ureterectomy and effects of salvage radical nephroureterectomy in patients with distal ureteral urothelial carcinoma.

We compared the progression patterns after radical nephroureterectomy (RNU) and elective distal ureterectomy (DU) in patients with urothelial carcinoma of the distal ureter. Between Jan 2011 and Dec 2020, 127 patients who underwent RNU and 46 who underwent elective DU for distal ureteral cancer were enrolled in this study. The patterns of progression and upper tract recurrence were compared between the two groups. Progression was defined as a local recurrence and/or distant metastasis after surgery. Upper tract recurrence and subsequent treatment in patients with DU were analyzed. Progression occurred in 35 (27.6%) and 10 (21.7%) patients in the RNU and DU groups, respectively. The progression pattern was not significantly different (p = 0.441), and the most common progression site was the lymph nodes in both groups. Multivariate logistic regression analysis revealed that pT2 stage, concomitant lymphovascular invasion, and nodal stage were significant predictors of disease progression. Upper tract recurrence was observed in nine (19.6%) patients with DU, and six (66.7%) patients had a prior history of bladder tumor. All patients with upper tract recurrence after DU were managed with salvage RNU. Elective DU with or without salvage treatment was not a risk factor for disease progression (p = 0.736), overall survival (p = 0.457), cancer-specific survival (p = 0.169), or intravesical recurrence-free survival (p = 0.921). In terms of progression patterns and oncological outcomes, there was no difference between patients who underwent RNU and elective DU with/without salvage treatment. Elective DU should be considered as a therapeutic option for distal ureter tumor.

Correction: Mobile App-Based Lifestyle Coaching Intervention for Patients With Nonalcoholic Fatty Liver Disease: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/49839.].

Probiotic Lactiplantibacillus plantarum KU210152 and its fermented soy milk attenuates oxidative stress in neuroblastoma cells.

We evaluated the probiotic properties and neuroprotective effects of Lactiplantibacillus plantarum KU210152 and its application in soy milk. L. plantarum KU210152 exhibited high tolerance to artificial gastrointestinal conditions, high adhesion to intestinal cells (HT-29), and safe enzyme production. Conditioned medium acquired from HT-29 cells treated with heat-killed lactic acid bacteria (LAB-CM) was used to evaluate the neuroprotective effects. The CM exhibited neuroprotective effects via cell viability assay, morphological observations, and suppression of ROS production. Heat-killed L. plantarum KU210152 increased brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase (TH) expression in HT-29 cells. In SH-SY5Y cells, pretreatment with L. plantarum KU210152 CM decreased Bax/Bcl-2 ratio and upregulated BDNF and TH expression. The CM inhibited caspase-9 and caspase-3 activities. The neuroprotective effects of L. plantarum KU210152 were also confirmed in fermented soy milk. Therefore, both L. plantarum KU210152 and the fermented soy milk can be used as functional ingredients with neuroprotective effects against oxidative stress.

A Liver Stiffness-Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma.

BACKGROUND & AIMS: The existing hepatocellular carcinoma (HCC) risk scores have modest accuracy, and most are specific to chronic hepatitis B infection. In this study, we developed and validated a liver stiffness-based machine learning algorithm (ML) for prediction and risk stratification of HCC in various chronic liver diseases (CLDs). METHODS: MLs were trained for prediction of HCC in 5155 adult patients with various CLDs in Korea and further tested in 2 prospective cohorts from Hong Kong (HK) (N = 2732) and Europe (N = 2384). Model performance was assessed according to Harrell's C-index and time-dependent receiver operating characteristic (ROC) curve. RESULTS: We developed the SMART-HCC score, a liver stiffness-based ML HCC risk score, with liver stiffness measurement ranked as the most important among 9 clinical features. The Harrell's C-index of the SMART-HCC score in HK and Europe validation cohorts were 0.89 (95% confidence interval, 0.85-0.92) and 0.91 (95% confidence interval, 0.87-0.95), respectively. The area under ROC curves of the SMART-HCC score for HCC in 5 years was ≥0.89 in both validation cohorts. The performance of SMART-HCC score was significantly better than existing HCC risk scores including aMAP score, Toronto HCC risk index, and 7 hepatitis B-related risk scores. Using dual cutoffs of 0.043 and 0.080, the annual HCC incidence was 0.09%-0.11% for low-risk group and 2.54%-4.64% for high-risk group in the HK and Europe validation cohorts. CONCLUSIONS: The SMART-HCC score is a useful machine learning-based tool for clinicians to stratify HCC risk in patients with CLDs.

Cases of Pernio-Like Lesions after mRNA-1273 Vaccination with Clinical and Pathological Features: A Single-Center Experience.

The currently available coronavirus disease 2019 (COVID-19) vaccines in South Korea include mRNA (Moderna® and Pfizer®) and adenoviral vector (AstraZeneca® and Janssen®) vaccines. Dermatologic side effects of COVID-19 vaccines range from local injection site reactions to systemic eruptions, including morbilliform rashes or erythema multiforme. Pernio-like lesions, one of the most common cutaneous manifestations of COVID-19, have been rarely reported post-vaccination. Herein, we report four cases of pernio-like lesions, which were detected in a single tertiary hospital within 2 months, after the first dose of mRNA-1273 (Moderna®) vaccination was administered. In this study, we discuss the clinical and pathological features of our cases and compare them with those of previously reported cases of pernio-like lesions after COVID-19 vaccination. It is pivotal to realize that perniolike lesions can be a possible side effect of COVID-19 vaccination and that the number of patients experiencing this side effect is bound to be quite high in real-world clinical settings.

Mapping of systematic reviews on traditional medicine across health conditions: a protocol for a systematic map.

INTRODUCTION: Traditional medicine (TM) is an important part of healthcare either as the main healthcare system or as a complement to conventional medicine. The effectiveness of TM has been assessed in clinical trials that have been synthesised into thousands of systematic reviews (SRs). This study is commissioned by the World Health Organization (WHO) and is aimed at providing a systematic map of SRs of TM interventions across health conditions, as well as identifying gaps in the research literature in order to prioritise future primary research. METHODS AND ANALYSIS: This is the protocol for a systematic map of SRs reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search 17 electronic databases to identify SRs of TM. The literature search covers the last 5 years, from January 2018 to December 2022. At least two independent reviewers will perform the database search, screening of eligible SRs, data extraction and quality assessments using the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR 2). The characteristics and extent of SRs will be analysed according to disease classification, and type of TM intervention, and visualised by means of (interactive) graphical maps. ETHICS AND DISSEMINATION: Ethical approval is not required as this is a systematic map of published studies. The findings of the study will be disseminated through online-available maps, presentations and scientific publications. PROSPERO REGISTRATION NUMBER: CRD42023416355.

Different Outcomes According to Needling Point Location Used in Sham Acupuncture for Cancer-Related Pain: A Systematic Review and Network Meta-Analysis.

Numerous acupuncture studies have been conducted on cancer-related pain; however, its efficacy compared to sham acupuncture remains controversial. We confirmed whether the outcome of acupuncture differs according to the needling points of sham acupuncture for cancer-related pain. We searched 10 databases on 23 May 2023 to screen acupuncture trials using sham acupuncture or waiting list as controls for cancer-related pain. Sham acupuncture was classified into two types, depending on whether the needling was applied at the same locations as verum acupuncture (SATV) or not (SATS). A network meta-analysis (NMA) was performed on the basis of a frequentist approach to assess pain severity. Eight studies (n = 574 participants) were included in the review, seven of which (n = 527 participants) were included in the NMA. The pain severity was not significantly different between SATV and verum acupuncture, but verum acupuncture significantly improved pain severity compared to SATS. The risk of bias affecting the comparisons between the verum and sham acupuncture was generally low. Previous acupuncture trials for cancer-related pain showed differing outcomes of sham and verum acupuncture, depending on the needling points of sham acupuncture. The application of SATV cannot be considered a true placebo, which leads to an underestimation of the efficacy of verum acupuncture.

Inhibition of Dickkopf-1 enhances the anti-tumor efficacy of sorafenib via inhibition of the PI3K/Akt and Wnt/ß-catenin pathways in hepatocellular carcinoma.

BACKGROUND: Sorafenib improves the overall survival in patients with advanced hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) is commonly overexpressed in HCC. In this study, we investigated whether the inhibition of DKK1 enhances the anti-tumor efficacy of sorafenib in HCC. METHODS: HCC cells were treated with sorafenib and WAY-262611, which is an inhibitor of DKK1. Transgenic mouse models were also developed using hydrodynamic tail vein injection. Mice were orally administered with sorafenib (32 mg/kg), WAY-262611 (16 mg/kg), or sorafenib + WAY-262611 for 10 days. Mechanisms of sorafenib and WAY-262611 were explored via western blotting, immunostaining, and RNA sequencing. RESULTS: DKK1 was significantly overexpressed in patients with HCC than in the healthy controls and patients with liver diseases except HCC (all P < 0.05). Compared with sorafenib alone, sorafenib + WAY-262611 significantly inhibited the cell viability, invasion, migration, and colony formation by promoting apoptosis and altering the cell cycles in HCC cells (all P < 0.05). Moreover, sorafenib + WAY-262611 decreased the p110α, phospho-Akt (all P < 0.05), active ß-catenin (all P < 0.05) and phospho-GSK-3ß (Ser9) expression levels, while increasing the phospho-GSK-3ß (Tyr216) expression levels compared with those in the sorafenib alone in vitro and in vivo. In addition, sorafenib + WAY-262611 inhibited tumor progression by regulating cell proliferation and apoptosis, significantly better than sorafenib alone in mouse models. CONCLUSIONS: Our results indicate that DKK1 inhibition significantly enhances the anti-tumor efficacy of sorafenib by inhibiting the PI3K/Akt and Wnt/ß-catenin pathways via regulation of GSK3ß activity, suggesting a novel therapeutic strategy for HCC. Video Abstract.

Tissue Circular RNA_0004018 and 0003570 as Novel Prognostic Biomarkers for Hepatitis B-Related Hepatocellular Carcinoma.

The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue samples of HCC and adjacent non-HCC, the relative expression profiles of hsa_circ_0004018 and hsa_circ_0003570 were determined using quantitative real-time polymerase chain reactions. The cut-off values were the median expression of each of the two circRNAs in 86 patients with HBV-HCC. The combination group comprised patients with high levels of the two circRNAs. Clinicopathological features, body composition profiles at the L3 level, and survival rates were investigated. The expression of hsa_circ_0004018 and hsa_circ_0003570 was downregulated in HCC tissues compared with non-HCC tissues. High expression levels of hsa_circ_0003570 (hazard ratio (HR), 0.437; p = 0.009) and hsa_circ_0004018 (HR, 0.435; p = 0.005) were inversely independent risk factors for overall and progression-free survival in patients with HBV-HCC, whereas the combination group was also an inversely independent risk factor for overall (HR, 0.399; p = 0.005) and progression-free survival (HR, 0.422; p = 0.003) in patients with HBV-HCC. The combination of hsa_circ_0003570 and hsa_circ_0004018 may be a potential prognostic biomarker for HBV-HCC.

The Effect of Model for End-Stage Liver Disease 3.0 on Disparities between Patients with and without Hepatocellular Carcinoma in Korea.

PURPOSE: The model for end-stage liver disease (MELD) 3.0 has recently been suggested for determining liver allocation. We aimed to apply MELD 3.0 to a Korean population and to discover differences between patients with and without hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study is a retrospective study of 2203 patients diagnosed with liver cirrhosis at Severance Hospital between 2016-2022. Harrell's concordance index was used to validate the ability of MELD scores to predict 90-day survival. RESULTS: During a mean follow-up of 12.9 months, 90-day survival was 61.9% in all patients, 50.4% in the HCC patients, and 74.8% in the non-HCC patients. Within the HCC patients, the concordance index for patients on the waitlist was 0.653 using MELD, which increased to 0.753 using MELD 3.0. Among waitlisted patients, the 90-day survival of HCC patients was worse than that of non-HCC patients with MELD scores of 31-37 only (69.7% vs. 30.0%, p=0.001). Applying MELD 3.0, the 90-day survival of HCC patients was worse than that of non-HCC patients across a wider range of MELD 3.0 scores, compared to MELD, with MELD 3.0 scores of 21-30 and 31-37 (82.0% vs. 72.5% and 72.3% vs. 24.3%, p=0.02 and p<0.001, respectively). CONCLUSION: MELD 3.0 predicted 90-day survival of the HCC patients more accurately than original MELD score; however, the disparity between HCC and non-HCC patients increased, particularly in patients with MELD scores of 21-30. Therefore, a novel exception score is needed or the current exception score system should be modified.

Needling Point Location Used in Sham Acupuncture for Chronic Nonspecific Low Back Pain: A Systematic Review and Network Meta-Analysis.

Importance: When sham acupuncture is set as a control in evaluating acupuncture, the sham needling technique is usually different from acupuncture. However, the sham procedure is conducted either at the same points that are used for the acupuncture group or at nonindicated points. Objective: To assess whether the outcome of sham acupuncture varies according to the needling points in sham-controlled trials of acupuncture for chronic nonspecific low back pain (CLBP) as an example. Data sources: Searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the Allied and Complementary Medicine Database were conducted on February 12, 2023. Study selection: Randomized clinical trials (RCTs) assessing the outcomes of acupuncture in sham acupuncture-controlled or waiting list-controlled trials on CLBP were included. Data extraction and synthesis: Two researchers independently extracted data on study characteristics and outcomes and assessed quality. Sham acupuncture was classified according to whether it was conducted at the same acupuncture points used in the acupuncture group, referred to as sham acupuncture therapy (verum) (SATV) or at different points, referred to as sham acupuncture therapy (sham) (SATS). Clinical similarity, transitivity, and consistency tests were conducted, followed by a random-effects frequentist network meta-analysis (NMA). Main outcomes and measures: The primary outcome was pain, and the secondary outcome was back-specific function. The first assessment after the end of treatment was chosen for analysis. Effect sizes are reported as standardized mean differences (SMD) with 95% CIs. The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence for findings was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Ten RCTs involving 4379 participants were included. In comparison with SATS, acupuncture was significantly associated with improvements in both pain (SMD, -0.33; 95% CI, -0.52 to -0.15) and function outcomes (SMD, -0.13; 95% CI, -0.25 to -0.02); however, there were no differences between acupuncture and SATV. In comparison with SATS, SATV was significantly associated with better pain (SMD, -0.45; 95% CI, -0.88 to -0.03) and function outcomes (SMD, -0.30; 95% CI, -0.56 to -0.05). The risk of bias that could affect the interpretation of the results was usually low, and the certainty of evidence was moderate to low. Conclusions and relevance: In this NMA, sham acupuncture needling at the same points as those in acupuncture was not a true placebo control for assessing the efficacy of acupuncture for CLBP and might underestimate the outcome of acupuncture in clinical settings.