Cox model risk score to predict survival of intrahepatic cholangiocarcinoma after ultrasound-guided ablation.

PURPOSE: To explore factors associated with overall survival (OS) and progression-free survival (PFS) of intrahepatic cholangiocarcinoma (iCCA) after ultrasound-guided ablation and establish a model for survival risk evaluation. METHODS: Data from 54 patients with 86 iCCAs between August 2008 and October 2022 were retrospectively analyzed. Cox regression were used to analyze the effects of clinical features on OS and PFS. Based on the variables screened by multivariable analysis, a model was established to predict the survival of the patients. Time-dependent receiver operating characteristic (timeROC) curve was constructed to evaluate the performance of this model. The model was further verified by bootstrap validation. The clinical usefulness of the model was evaluated by the decision curve analysis (DCA). RESULTS: During follow up, 39 patients died and 49 patients developed recurrence. Pre-ablation CA199 level > 140 U/ml was the only independent predictor of poor PFS. Age > 70 years, early recurrence, maximal diameter of tumor size > 1.5 cm and pre-ablation CA199 level > 140 U/ml were significantly associated with poor OS. Then a model was established based on the above four variables. The areas under the timeROC curve (AUC) for 1-year, 2-year, 3-year, 5-year were 0.767, 0.854, 0.791 and 0.848, respectively. After bootstrapping for 1000 repetitions, the AUCs were similar to the initial model. DCA also demonstrated that the model had good positive net benefits. CONCLUSION: The established model in this study could predict the survival outcomes of the patients with iCCA after thermal ablation, but further research was needed to validate the results.

Three-dimensional ultrasound fusion imaging in precise needle placement for thermal ablation of hepatocellular carcinoma.

PURPOSE: To investigate the value of three-dimensional ultrasound fusion imaging (3DUS FI) technique for guiding needle placement in hepatocellular carcinoma (HCC) thermal ablation. METHODS: A total of 57 patients with 60 HCCs with 3DUS FI-guided thermal ablation were retrospectively included in the study. 3DUS volume data of liver were acquired preoperatively by freehand scanning with the tumor and predetermined 5 mm ablative margin automatically segmented. Plan of needle placement was made through a predetermined simulated ablation zone to ensure a 5 mm ablative margin with the coverage rate toward tumor and ablative margin. With real-time ultrasound and 3DUS fusion imaging, ablation needles were placed according to the plan. After ablation, the ablative margin was immediately evaluated by contrast-enhanced ultrasound and 3DUS fusion imaging. The rate of adequate ablative margin, complete response (CR), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) was evaluated. RESULTS: According to postoperative contrast-enhanced CT or MR imaging, the complete response rate was 100% (60/60), and 83% of tumors (30/36) achieved adequate ablative margin (>5 mm) three-dimensionally. During the follow-up period of 6.0-42.6 months, LTP occurred in 5 lesions, with 1- and 2-year LTP rates being 7.0% and 9.4%. The 1- and 2-year DFS rates were 76.1% and 65.6%, and 1- and 2-year OS rates were 98.1% and 94.0%. No major complications or ablation-related deaths were observed in any patients. CONCLUSIONS: Three-dimensional ultrasound fusion imaging technique may improve the needle placement of thermal ablation for HCC and reduce the rate of LTP.

Interpretable artificial intelligence-based app assists inexperienced radiologists in diagnosing biliary atresia from sonographic gallbladder images.

BACKGROUND: A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model's performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. METHODS: A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). RESULTS: The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. CONCLUSIONS: The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.

Quantitative Parameters of Contrast-Enhanced Ultrasound Predicting the Response to Combined Immune Checkpoint Inhibitor and Anti-angiogenesis Therapies for Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The aim of the work described here was to explore the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the response of combined immune checkpoint inhibitor (ICI) and anti-angiogenesis therapies for unresectable hepatocellular carcinoma (HCC). METHODS: Sixty-six HCC patients who underwent combined ICI and anti-angiogenesis therapies were prospectively enrolled. A CEUS examination was performed at baseline, and tumor perfusion parameters were obtained with perfusion quantification software. The differences in CEUS quantitative parameters between the responder and non-responder groups were compared, and the correlations between CEUS parameters and progression-free survival (PFS) was evaluated. RESULTS: The objective response rate (ORR) was 21.2%. The values of rising time (RT) ratio, time to peak ratio, fall time ratio, peak enhancement ratio, wash-in rate ratio, wash-in perfusion index ratio and wash-out rate ratio differed significantly differed between the responder and non-responder groups (all p values < 0.05). Multivariable logistic regression analysis revealed that the RT ratio was the only independent factor associated with the ORR (odds ratio = 0.007, 95% confidence interval: 0.000-0.307, p = 0.010). The median RT ratios of the responder and non-responder groups were 36.9 and 58.9, respectively (p = 0.006). The appropriate cutoff point of the RT ratio was 80.1, determined with the X-tile program. Survival analysis indicated high PFS for the patients with a lower RT ratio (high RT ratio vs. low RT ratio = 4.4 mo vs. not reached, p = 0.001). CONCLUSION: CEUS quantitative parameters may predict the efficacy of ICI and anti-angiogenesis combined therapies for HCC.

3D fusion is superior to 2D point-to-point contrast-enhanced US to evaluate the ablative margin after RFA for hepatocellular carcinoma.

PURPOSE: To compare the efficiency of three-dimensional (3D) and two-dimensional (2D) contrast-enhanced ultrasound (CEUS)-derived techniques in evaluating the ablative margin (AM) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: In total, 98 patients with 98 HCCs were enrolled. The 2D CEUS point-to-point imaging (2D CEUS-PI) was conducted by comparing the pre- and post-RFA 2D CEUS images manually, and the 3D CEUS fusion imaging (3D CEUS-FI) was conducted by fusing the pre- and post-RFA 3D CEUS images automatically. These two techniques were compared in distinguishing an adequate AM ≥ 5 mm. Risk factors for local tumor progression (LTP) after RFA were analyzed by the Kaplan-Meier method with log-rank test. RESULTS: The mean registration time of 3D CEUS-FI and 2D CEUS-PI was 5.0 and 9.3 min, respectively (p < 0.0001). The kappa coefficient was 0.680 for agreement between 2D CEUS-PI and 3D CEUS-FI in the evaluation of AM (p < 0.0001). Tumors with AM < 5 mm by 2D CEUS-PI were all identified as AM < 5 mm by 3D CEUS-FI. Nonetheless, 16 (26%) tumors identified as AM ≥ 5 mm by 2D CEUS-PI were re-classified as AM < 5 mm by 3D CEUS-FI. During a median follow-up time of 31.2 months (range, 3.2-66.0 months), LTP was identified in 8 tumors. The estimated 1-/2-/3-year cumulative incidence of LTP was 4.4%, 8.1%, and 10.3%, respectively. Higher estimated cumulative incidence of LTP was identified in tumors with AM < 5 mm by 2D CEUS-PI (at 3-year, 27.2% vs 0%; p < 0.001), and by 3D CEUS-FI (at 3-year, 20.7% vs 0%; p = 0.004). CONCLUSION: 3D CEUS-FI excelled in the evaluation of AM when compared with 2D CEUS-PI. With equivalent efficacy in the prediction of LTP, 3D CEUS-FI was superior to 2D CEUS-PI for its automatic and time-saving procedure. CLINICAL RELEVANCE STATEMENT: 3D CEUS fusion imaging may serve as an effective tool in evaluating ablative margin and predicting local tumor progression after RFA in HCC. KEY POINTS: • Both 2D and 3D CEUS-derived techniques could evaluate ablative margin (AM) after RFA for hepatocellular carcinoma. • 3D CEUS fusion imaging was more precise in the evaluation of AM compared to 2D CEUS point-to-point imaging, with advantages of its automatic and time-saving procedure. • An inadequate AM < 5 mm evaluated by CEUS-derived techniques was the only risk factor of LTP after RFA for hepatocellular carcinoma (p < 0.001 for 2D CEUS point-to-point imaging, and p = 0.004 for 3D CEUS fusion imaging).

A Systematic Review and Meta-analysis of Renin-angiotensin System Inhibitors and Angiotensin Receptor Neprilysin Inhibitors in Preventing Recurrence After Atrial Fibrillation Ablation.

ABSTRACT: To systematically evaluate the efficacy and safety of renin-angiotensin system inhibitors (RASIs) and angiotensin receptor neprilysin inhibitors in preventing the recurrence of atrial fibrillation after atrial fibrillation ablation, we have written this meta-analysis. We systematically searched randomized controlled trials or cohort studies on RASIs and angiotensin receptor neprilysin inhibitor-sacubitril/valsartan (SV) in preventing the recurrence of atrial fibrillation. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Afterward, the meta-analysis was performed using RevMan 5.3 software. This meta-analysis results showed that the recurrence rate of atrial fibrillation after ablation in subjects using RASIs was lower than that in subjects not using them [relative risk = 0.85, 95% confidence interval (CI) (0.72-0.99), P = 0.03]; the recurrence rate in subjects using SV was lower than that in subjects using RASIs [RR= 0.50, 95% CI (0.37-0.68), P < 0.00001]. These results show that both the use of RASIs and SV can prevent the recurrence of after atrial fibrillation ablation, among which the use of SV is more effective.

Development and Assessment of Nomogram Based on AFP Response for Patients with Unresectable Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. METHODS: A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan-Meier analysis with the log-rank test was used to compare different risk groups. RESULTS: The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02-4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02-11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18-0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). CONCLUSION: The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis

ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Rapid health technology assessment of the novel endonuclease inhibitor baloxavir for the treatment of influenza.

Through a Rapid Health Technology Assessment (RHTA), we evaluated the efficacy, safety and cost-effectiveness of baloxavir in the treatment of influenza, providing the necessary scientific information and evidence-based basis for healthcare professionals and health insurance decision-makers in making rational selections. Through systematic searches of Pubmed, Embase, Web of Science, The Cochrane Register of Clinical Trials database and the official website of Health Technology Assessment (HTA) agencies, we collected systematic reviews (SR)/Meta-analysis, cost-effectiveness evaluations and HTA reports of baloxavir for influenza, with a search time frame of date of database establishment to July 31, 2022. We then performed data extraction, literature screening and quality evaluation on the literature that met our selection criteria, after which the results of the studies were pooled and qualitatively described for analysis. 10 studies were included, including 6 SR/Meta-analysis, three economics studies, and 1 HTA report. In terms of efficacy, baloxavir had an advantage over oseltamivir for all three types of influenza patients (otherwise healthy patients, high-risk patients, and patients are not separated into groups with and without underlying health conditions) concerning change in virus titer from baseline at 24 and 48 h; about otherwise healthy patients and high-risk patients, baloxavir had an advantage over peramivir; pertaining to high-risk patients, baloxavir had an advantage over laninamivir; the above differences between groups were all statistically significant. In terms of safety, in otherwise healthy patients and patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of DRAEs and nausea compared with oseltamivir, as well as significantly reduced the incidence of DRAEs compared with laninamivir; in patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of AEs and diarrhoea compared with oseltamivir; the differences between the above groups were all statistically significant. Economically, in Japanese adult influenza patients and high-risk populations, the Quality-Adjusted Life Years (QALY) of baloxavir slightly triumphed over that of laninamivir (Δ = 0.000112 and 0.00209 QALY per 1 patient, respectively); moreover, the incremental cost-effectiveness ratio (ICER: 2,231,260 and 68,855 yen/QALY, respectively) was below the willingness-to-pay (WTP) threshold (5,000,000 yen/QALY); in Chinese adult influenza patients without underlying diseases and adult high-risk influenza patients, baloxavir had a higher QALY compared with oseltamivir (Δ = 0.000246 and 0.000186 respectively), however, their ICER (12,230 and 64,956 RMB/QALY) was above the local WTP threshold (10,000 RMB/QALY) and thus did not provide a cost-effectiveness advantage. Baloxavir had a favorable efficacy and safety profile compared to neuraminidase inhibitors (NAIs), and the currently available evidence suggested that it had an economic advantage only in Japan.

Predicting Infectious Complications after Percutaneous Thermal Ablation of Liver Malignancies: A 12-year Single-Center Experience.

Background Infectious complications after percutaneous thermal ablation are seldom discussed, but better understanding of risk factors and early prediction is critical. Purpose To estimate the incidence of infectious complications after percutaneous thermal ablation of liver malignancies and to develop prediction models. Materials and Methods This single-center retrospective study reviewed the data of 3167 patients who underwent 7545 percutaneous US-guided thermal ablation procedures of liver malignancies between January 2010 and January 2022. All procedures with infectious complications were included as the case group. For each case, one treatment date-matched control subject without infection was randomly selected following a nested case-control design. Independent factors of overall and hepatobiliary infection were investigated with multivariable logistic regression. Results A total of 80 patients (median age, 59 years; IQR, 51-68 years; 64 men, 16 women) developed infectious complications after 80 ablation procedures; the incidence was 1.1% (80 of 7545 procedures). Of those with infection, 18% (14 of 80 patients) were severe, and 10% (eight of 80 patients) died as a result. Independent risk factors for overall infectious complication included prior biliary intervention (odds ratio [OR], 18.6; 95% CI: 4, 86; P < .001), prior transarterial chemoembolization (TACE) (OR, 2.4; 95% CI: 1.0, 5.8; P = .045), and the largest tumor size (OR, 1.9; 95% CI: 1.3, 2.8; P = .002); on this basis, subcapsular location was an additional risk factor of hepatobiliary infection. Prediction models for overall and hepatobiliary infection had an area under the receiver operating characteristics curve (AUC) of 0.77 and 0.82, respectively, both of which showed better AUC compared with the models, including prior biliary intervention alone (AUC = 0.63 and 0.65, respectively; P = .01 and P = .005, respectively). Conclusion Infectious complications after percutaneous thermal ablation of liver malignancies were uncommon but potentially fatal. Independent predictors were prior biliary intervention, prior transarterial chemoembolization, and the largest tumor size. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ben-Arie and Sosna in this issue.

Treatment outcomes after radiofrequency ablation in patients with non-B non-C hepatocellular carcinoma within Milan criteria: comparison with HBV-related hepatocellular carcinoma.

PURPOSE: This study aims to evaluate the treatment outcomes of radiofrequency ablation (RFA) for patients with non-B non-C hepatocellular carcinoma (HCC) (NBNC-HCC) within Milan criteria, as well as to compare them with those of patients with hepatitis B virus (HBV)-related HCC (HBV-HCC). METHODS: From January 2007 to February 2020, 303 patients with primary HCC who underwent RFA were retrospectively reviewed, including 259 patients with HBV-HCC (HBV-HCC group) and 44 patients with NBNC-HCC (NBNC-HCC group). The clinical characteristics and treatment survivals were evaluated and compared. Moreover, the propensity score matching was used to reduce selection bias. RESULTS: A significantly lower proportion of cirrhosis was observed in the NBNC-HCC group (p = .048). Before propensity score matching, local tumor progression, disease-free survival, and overall survival after RFA showed no significant differences between the two groups (all p > .05). After matching, the overall survival rates in the NBNC-HCC group were significantly better than those in the HBV-HCC group (p = .042). Moreover, for patients with NBNC-HCC, tumor size (hazard ratio = 8.749, 95% confidence interval, 1.599-47.849; p = .012) was the only independent predictor of local tumor progression. CONCLUSIONS: Patients with NBNC-HCC within the Milan criteria after RFA had better long-term survival than patients with HBV-HCC, although larger, prospective and multicenter trials are required to validate these results.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis.

bladder based on a systematic review and network meta-analysis approach. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. RESULT: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. CONCLUSION: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Clinical research progress of novel biologics for the treatment of lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the loss of immune tolerance. Lupus nephritis (LN) is one of the most common manifestations of severe organ damage in SLE, and also an important cause of disability and death. Its pathogenesis is associated with immune abnormalities such as immune cells, cytokines, and immune complex deposition. Traditional immunosuppressive therapy has been unable to meet the treatment needs of patients while bringing them toxic effects. In recent years, targeted therapies have emerged, and several novel biologics have gradually entered people's sight. This review will briefly introduce the pathogenesis of LN and the mechanism of biological targets, and summarize and analyze the clinical trials of new biologics for treating LN. Although not all biologics show positive results in clinical trials, the experience learned from these trials can help researchers adjust and plan future trial programs to seek better treatment methods.

Efficacy and safety of novel biologics in the treatment of lupus nephritis based on registered clinical trials: a systematic review and network meta-analysis.

To compare the clinical effectiveness and safety of novel biologics for the treatment of lupus nephritis based on a reticulated meta-analysis approach. Registered clinical trials in 4 major databases (PubMed, Embase, Web of Science, The Cochrane Register of Clinical Trials) and ClinicalTrials.gov were systematically searched with a search time frame of build to June 2022. And we screened registered randomized controlled clinical trials of biologics for the treatment of lupus nephritis according to the protocol's nadir criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 and Review Manager 5.3 software to compare and rank differences in effectiveness and safety between the biologics. A total of 10 registered randomized controlled clinical trials involving 2148 subjects were included in this study. The interventions were ranked from best to worst in terms of the primary outcome indicator of effectiveness, renal complete remission: belimumab > anifrolumab (900 + 300) mg > obinutuzumab > ocrelizumab 400 mg > abatacept 30/10 mg/kg > belimumab + rituximab > abatacept 10/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > ocrelizumab 1000 mg > rituximab > anifrolumab 300 mg, belimumab was superior to placebo [OR = 1.75, 95% CI (1.13, 2.70)] and anifrolumab 300 mg [OR = 3.27, 95% CI (1.05, 10.14)], anifrolumab (900 + 300) mg was superior to anifrolumab 300 mg [OR = 3.56, 95% CI (1.30, 9.76)], and all were statistically significant. The ranking of each intervention in terms of overall renal remission for secondary outcome indicators from best to worst was: obinutuzumab > belimumab + rituximab > anifrolumab (900 + 300) mg > ocrelizumab 1000 mg > ocrelizumab 400 mg > belimumab > rituximab 1000 mg > abatacept 30/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > abatacept 10/10 mg/kg > anifrolumab 300 mg, obinutuzumab was superior to placebo [OR = 2.27, 95% CI (1.11, 4.67)] and belimumab was also superior to placebo [OR = 1.56, 95% CI (1.07, 2.27)], and all were statistically significant. In terms of safety, with a focus on serious adverse events and serious infections, the results were: Serious adverse events at 1 year of monitoring occurred better with ocrelizumab 1000 mg than ocrelizumab 400 mg [OR = 0.51, 95% CI (0.29, 0.89)] and were statistically different; serious adverse events at 2 years of monitoring infection adverse events occurred better with obinutuzumab than with abatacept (30/10 + 10/10) mg/kg [OR = 0.24, 95% CI (0.07, 0.81)] and were statistically different. The safety of the new biologics in combination with conventional standard therapies is generally good, but it is belimumab and obinutuzumab that are most effective in achieving complete and overall remission in the kidney. This study protocol has been registered with PROSPERO, with a registration number of CRD42021262498.

Advances in Studies of Chiglitazar Sodium, a Novel PPAR Pan-Agonist, for the Treatment of Type 2 Diabetes Mellitus.

Chiglitazar sodium is a new peroxisome proliferator-activated receptor (PPAR) pan-agonist with independent intellectual property rights in China. It can treat type 2 diabetes mellitus and regulate metabolism by modestly activating PPARα, PPARγ, and PPARδ to improve insulin sensitivity, regulate blood glucose, and promote fatty acid oxidation and utilization. Chiglitazar sodium has a significant insulin-sensitizing effect and is advantageous in reducing fasting and postprandial blood glucose levels, particularly at the 48 mg dose in patients with concomitant high triglycerides in terms of blood glucose and triglyceride level control.

Comparison of non-radiomics imaging features and radiomics models based on contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma within 5 cm.

OBJECTIVES: The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. METHODS: Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. RESULTS: Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. CONCLUSIONS: Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. CLINICAL RELEVANCE STATEMENT: Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. KEY POINTS: • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.

Efficacy and safety of vibegron compared with mirabegron for overactive bladder: A systematic review and network meta-analysis.

OBJECTIVES: The aim of this study was to indirectly compare the efficacy and safety of mirabegron and vibegron in patients with overactive bladder. METHODS: A systematic search was performed on Pubmed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases to identify studies from the date of database inception to January 1, 2022. All randomized controlled trials comparing mirabegron or vibegron with tolterodine, imidafenacin, or placebo were eligible. One reviewer extracted data, and a second reviewer checked. Included trials were assessed for similarity, and networks were developed using Stata 16.0 software. Mean differences for continuous variables and odds ratios for dichotomous variables together with their 95% confidence intervals (CIs) were used to rank treatments and compare the differences, respectively. RESULTS: A total of 11 randomized controlled trials and 10 806 patients were included. For each outcome, results for all licensed treatment doses were included. Both vibegron and mirabegron were more efficacious than placebo at reducing the frequency of micturition, incontinence, urgency, urgency incontinence, and nocturia. Vibegron was more efficacious than mirabegron in reducing mean voided volume/micturition (95% CI [5.15, 14.98]). Safety outcomes for vibegron and mirabegron were similar to those in the placebo group, except for mirabegron, which had a higher risk of nasopharyngitis and cardiovascular adverse events than placebo. CONCLUSIONS: Both drugs seem to be comparable and well tolerated, particularly as direct comparisons are not available. However, vibegron may be more effective than mirabegron in reducing mean voided volume.

Knowledge mapping of image-guided tumor ablation and immunity: A bibliometric analysis.

Background: Various ablation techniques have been successfully applied in tumor therapy by locally destroying tumor. In the process of tumor ablation, a large number of tumor cell debris is released, which can be used as a source of tumor antigens and trigger a series of immune responses. With the deepening of the research on the immune microenvironment and immunotherapy, researches exploring tumor ablation and immunity are continuously published. However, no research has systematically analyzed the intellectual landscape and emerging trends for tumor ablation and immunity using scientometric analysis. Therefore, this study aimed to conduct a bibliometric analysis to quantify and identify the status quo and trend of tumor ablation and immunity. Methods: Data of publications were downloaded from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to conduct bibliometric analysis to evaluate the contribution and co-occurrence relationship of different countries/regions, institutions and authors in the field, and to determine the research hotspots in this field. Results: By searching in the database, a total of 3531 English articles published between 2012 and 2021 were obtained. We observed rapid growth in the number of publications since 2012. The two most active countries were China and the United States, with more than 1,000 articles. Chinese Academy of Sciences contributed the most publications (n = 153). Jibing Chen and Xianzheng Zhang might have a keen interest in tumor ablation and immunity, with more publications (n = 14; n = 13). Among the top 10 co-cited authors, Castano AP (284 citations) was ranked first, followed by Agostinis P (270 citations) and Chen Qian (246 citations). According to the co-occurrence and cluster analysis, the results indicated that the focus of research was "photothermal therapy" and "immune checkpoint blockade". Conclusions: In the past decade, the neighborhood of tumor ablation domain immunity has been paid more and more attention. Nowadays, the research hotspots in this field are mainly focused on exploring the immunological mechanism in photothermal therapy to improve its efficacy, and the combination of ablation therapy and immune checkpoint inhibitor therapy.

Long-term outcomes of combined radiofrequency ablation and multipronged ethanol ablation for the treatment of unfavorable hepatocellular carcinoma

PURPOSE: To evaluate the local efficacy, safety, and long-term outcomes of combined radiofrequency ablation (RFA) and multipronged ethanol ablation (EA) in the treatment of unfavorable hepatocellular carcinoma (HCC) and to determine the prognostic factors for survival. METHODS: Between August 2009 and December 2017, 98 patients with 110 unfavorable HCC nodules who underwent combined RFA and multipronged EA were retrospectively enrolled in the study. Unfavorable HCC was defined as a medium (3.1-5.0 cm) or large (5.1-7.0 cm) HCC nodule, a tumor located at a high-risk site, or a perivascular tumor. The treatment response, overall survival (OS), and recurrence-free survival (RFS) were analyzed. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic factors. RESULTS: Complete ablation was obtained in 80.9% (89/110) of the tumors after initial treatment. Major complications were observed in 3 (3.1%) patients. The cumulative incidence of local tumor progression (LTP) was 23.5% at five years, and no variable was found to be an independent predictive factor for LTP. The five-year OS and RFS rates were 41.9% and 34.0%, respectively. Multivariate analysis showed that the serum alpha-fetoprotein level, tumor size, presence of residual tumor after ablation, and extrahepatic metastases were significant prognostic factors for OS (P = 0.023, P = 0.030, P = 0.001, and P = 0.010, respectively). Tumor type and the number of tumors were predictive factors for RFS (P = 0.029 and P = 0.001, respectively). A perivascular tumor was not an independent predictive factor for OS or RFS. CONCLUSION: Combined RFA and multipronged EA is a safe and effective treatment for unfavorable HCC, especially for perivascular tumors.