Comparative performance of ReMELD-Na, MELD 3.0 and established scores after TIPS for refractory ascites: A multicenter study.

Background The International Collaborative of NT-proBNP (ICON) study established NT-proBNP levels for the diagnosis and exclusion of acute heart failure for patients presenting to the emergency department (ED). Following the development of the Vitros Immunodiagnostic Products NT-proBNP II assay, a multi-center prospective study was conducted at 20 EDs across the United States. The study enrolled subjects presenting with dyspnea and clinical suspicion of heart failure (HF). Clinical performance of the Vitros Immunodiagnostic Products NT-proBNP II assay using the cutoffs established in the ICON study was compared to that of the Roche Elecsys proBNP II assay using samples from the multi-center study. Methods Clinical sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were determined by comparing the assay result interpretation using the corresponding cutoffs against the adjudicated diagnosis of HF/non-HF. Clinical performances were then compared between the VITROS NT-proBNP II and the Roche Elecsys proBNP II assays. Analyses were performed using both the age-independent and age-dependent cutoffs within and across age groups. Results After applying the rule-in cutoffs from the ICON study to the Vitros NTproBNP II and the Roche Elecsys proBNP II assay results, the clinical performance of the Vitros NT-proBNP II assay was comparable to that of the Roche Elecsys proBNP II assay (see Table 1). Conclusion The use of the ICON cutoffs resulted in high assay specificity to rulein HF and excellent sensitivity to ruleout HF. The Vitros NT-proBNP II assay demonstrated comparable clinical performance to the Roche Elecsys proBNP II assay.

Background and ObjectiveBladder cancer (BC), a prevalent malignancy, poses significant diagnostic and surveillance challenges due to its high recurrence rates and reliance on cystoscopy, an invasive procedure for diagnosis and monitoring. While urine‐based genomic and proteomic biomarkers offer promising non‐invasive alternatives, their clinical implementation remains limited. This review synthesizes evidence from multicentric studies on urinary biomarkers for BC and evaluates their potential in reducing unnecessary invasive cystoscopies.MethodsA comprehensive review of literature was conducted searching for multicentric studies on urine‐based genomic and proteomic biomarkers for BC detection and/or surveillance. MEDLINE/Pubmed, Embase and Scopus databases and BJUI, UroToday and European Urology Oncology registries were searched using National Library of Medicine Medical Subject Headings (MeSH) terms. Emphasis was placed on the comparative performance of diagnostic platforms across different research and clinical settings.Key Findings and LimitationsThe literature search yielded 51 reports that were included for analysis. Multicentre studies enhance the generalizability of findings by addressing inter‐laboratory variability and population diversity. This review underscores the importance of standardization, comparative performance analyses that these studies provide, and the potential for cost‐effective non‐invasive diagnostic tools. However, despite FDA approvals, no biomarker has replaced cystoscopy in clinical settings due to an inconsistent and insufficient combination of sensitivity, specificity and cost‐effectiveness parameters. The performance of AssureMDX and Enhanced CxBladder tests showed the most promise, but further large‐scale, standardized validation is still necessary.Conclusions and Clinical ImplicationsUrine‐based biomarkers have the potential to improve early BC detection and surveillance while reducing reliance on invasive procedures and costs related to the disease. Future efforts should prioritize cost‐effective, large‐scale multicentric studies to facilitate the adoption of these biomarkers into routine practice.

The use of terlipressin in cirrhotic patients with refractory ascites and normal renal function: A multicentric study

MRI-based multilevel radiomics and transformer features for predicting radiation-induced carotid artery injury after nasopharyngeal carcinoma radiotherapy: A multicenter study.

Cell-free and concentrated ascites reinfusion therapy versus large-volume paracentesis for the treatment of cirrhotic patients with refractory ascites: A multicenter prospective observational study.

BackgroundTransjugular intrahepatic portosystemic shunt (TIPS) is recommended for treating recurrent and refractory ascites. However, determining the target portal pressure gradient (PPG) has been inconclusive. This multicentre cohort study explored the post-TIPS PPG potential range associated with improving survival.MethodsThe study enrolled 276 patients, all of whom underwent covered TIPS for ascites treatment across four medical centers. The cumulative incidences of clinical outcomes were compared among groups categorized by potential PPG thresholds.ResultsDuring the whole follow-up period with a medium follow-up of 21.6 (7.5, 41.6) months, 122 (44.2%) experienced liver-related death, and 73 (26.4%) patients experienced a recurrence of ascites. Multivariable analysis revealed PPG < 7 mmHg (p = 0.007) and the recurrence of ascites (p = 0.033) are independent risk factors for survival, while the PPG ≥ 11 mmHg was an independent risk factor for the recurrence of ascites (p = 0.012). Patients with ≥ 7 mmHg had a lower rate of liver-related death than patients with post-TIPS PPG < 7 mmHg (51.0% vs 66.6%, p = 0.004), while those with post-TIPS PPG ≥ 11 mmHg exhibited a higher cumulative incidence of ascites compared to those with post-TIPS PPG < 11 mmHg (44.6% vs 33.7%, p = 0.023). The robustness of the results was confirmed.ConclusionOur study highlighted the existence of an optimal post-TIPS PPG range in patients with recurrent and refractory ascites. Patients may experience improved survival and ascites control with a post-TIPS PPG of 7–11 mmHg.Graphical

Transjugular intrahepatic portosystemic shunt (TIPS) is increasingly used in the management of refractory ascites. Controversy exists regarding the predictive factors of unfavorable outcomes, useful for patient selection. The primary aim was to identify predictive factors of 1-year survival or recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. The secondary aim was overall survival. Observational, retrospective, multicentric study, that included all cirrhotic patients treated with covered-TIPS for refractory ascites since 2001. Demographic, clinical, laboratory and hemodynamic data were collected at baseline and consecutively until dead, liver transplant or end of follow-up. The Cox model was used to identify predictive factors of overall survival. A Fine-Gray competing risk regression model was used to identify predictive factors of 1-year mortality or recurrent hepatic encephalopathy. A predictive nomogram was created based on those factors. In total 159 patients were included. Predictive factors of survival or recurrent severe encephalopathy were renal dysfunction [hazard ratio, 2.12 (95% CI, 1.11-4.04); P = 0.022], albumin [hazard ratio, 0.58 (95% CI, 0.34-0.97); P = 0.036], serum sodium [hazard ratio, 0.94 (95% CI, 0.89-0.98); P = 0.008] and international normalized ratio [hazard ratio 4.27 (95% CI, 1.41-12.88); P = 0.010]. In the competing risk analysis, predictive factors of 1-year mortality/recurrent severe encephalopathy in multivariate analysis were age [sub-distribution hazard ratio (sHR) 1.05 (95% CI, 1.02-1.09); P = 0.001], creatinine [sHR 1.55 (95% CI, 1.23-1.96); P = 0.001] and serum sodium [sHR 0.94 (95% CI, 0.90-0.99); P = 0.011] at baseline. Age, creatinine and sodium baseline levels strongly influence 1-year survival/recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. A simple nomogram accurately and easily identifies those patients with worse prognosis.

A deep learning fusion network trained with clinical and high-frequency ultrasound images in the multi-classification of skin diseases in comparison with dermatologists: a prospective and multicenter study

Regorafenib is a standard treatment option for patients with metastatic colorectal cancer (mCRC) refractory to conventional therapies. However, outcomes remain heterogeneous, and simple and reproducible prognostic tools applicable in routine clinical practice are needed to optimize patient selection. This study aimed to perform an external real-world validation of the REBECCA prognostic score and the Tabernero classification in a multicenter cohort of refractory mCRC patients treated with regorafenib. We conducted a retrospective multicenter study including 130 patients with refractory mCRC treated with regorafenib across five university hospitals in Galicia, Spain. Overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were analyzed according to the REBECCA prognostic score and the Tabernero classification. Kaplan–Meier estimates, log-rank tests, and chi-squared analyses were used to compare outcomes between prognostic subgroups. Median age was 63 years, and 94.6% of patients had ECOG performance status 0–1. Median OS and PFS were 6.7 and 2.9 months, respectively. According to the REBECCA prognostic score, median OS was 9.2, 6.9, and 5.3 months for low-, intermediate-, and high-risk groups, respectively (p = 0.138). In contrast, the Tabernero classification identified significant OS differences, with median OS of 10.5, 6.9, and 5.2 months in patients with best, good, and poor prognostic characteristics, respectively (p = 0.022). DCR was also significantly stratified by the Tabernero classification (48.0%, 21.1%, and 24.4%; p = 0.004). Treatment was well tolerated, with a safety profile consistent with previous studies. In this multicenter real-world study, the Tabernero classification demonstrated robust prognostic stratification in a real-world setting in refractory mCRC patients treated with regorafenib, whereas the REBECCA prognostic score showed limited discriminatory ability in this contemporary cohort. Given its simplicity, objectivity, and reproducibility, the Tabernero model may represent a practical tool to support prognostic assessment and clinical decision-making in routine practice.

ABSTRACTExosomal microRNAs (miRNAs) are candidates for liquid biopsies. Organoid culture systems enable long‐term expansion of the colon epithelium. This study evaluated exosomal miRNAs from colorectal cancer organoids for liquid biopsy. Organoids were established from normal colon and colorectal cancer tissues. Exosomes were isolated from conditioned media. miRNAs were extracted from exosomes and compared using microarray analysis. Exosomal miRNAs expression levels in the sera of healthy patients and patients with colorectal cancer were compared at a single institution. The multicenter study was validated using miRNAs upregulated in the serum of colorectal cancer patients, along with exosomal miRNAs reported to be upregulated in colorectal adenoma organoids and sera. A total of 44 exosomal miRNAs were commonly expressed in both normal colorectal epithelial cells and colorectal cancer organoids, whereas 59 were exclusively expressed in colorectal cancer organoids. In a single‐center cohort study, two exosomal miRNAs (miR‐4284 and miR‐5100) were upregulated in the serum of colorectal cancer patients. In a multicenter study, four exosomal miRNAs (miR‐4284, miR‐5100, miR‐1246, and miR‐1290) were upregulated in the serum of patients with colorectal cancer. The combination of these four exosomal miRNAs had comparable diagnostic performance to carcinoembryonic antigen, with an area under the curve of 0.75 (95% confidence interval: 0.65–0.83) versus 0.79 (95% confidence interval: 0.70–0.87). Combining the four miRNAs with carcinoembryonic antigen improved diagnostic accuracy, with an area under the curve of 0.82 (95% confidence interval: 0.74–0.89). Exosomal miRNAs derived from colorectal cancer organoids can serve as diagnostic biomarkers for colorectal cancer.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for portal hypertension‐related complications. However, careful selection of patients is crucial. The aim of this study was to evaluate the prognostic value of serum cholinesterase (CHE) for outcomes and mortality after TIPS insertion. In this multicenter study, 389 consecutive patients with cirrhosis receiving a TIPS at Hannover Medical School, University Hospital Essen, or Medical University of Vienna were included. The Hannover cohort (n = 200) was used to initially explore the role of CHE, whereas patients from Essen and Vienna served as a validation cohort (n = 189). Median age of the patients was 58 years and median Model for End‐Stage Liver Disease (MELD) score was 12. Multivariable analysis identified MELD score (hazard ratio [HR]: 1.16; P < 0.001) and CHE (HR: 0.61; P = 0.008) as independent predictors for 1‐year survival. Using the Youden Index, a CHE of 2.5 kU/L was identified as optimal threshold to predict post‐TIPS survival in the Hannover cohort (P < 0.001), which was confirmed in the validation cohort (P = 0.010). CHE < 2.5 kU/L was significantly associated with development of acute‐on‐chronic liver failure (P < 0.001) and hepatic encephalopathy (P = 0.006). Of note, CHE was also significantly linked to mortality in the subgroup of patients with refractory ascites (P = 0.001) as well as in patients with high MELD scores (P = 0.012) and with high‐risk FIPS scores (P = 0.004). After propensity score matching, mortality was similar in patients with ascites and CHE < 2.5 kU/L if treated by TIPS or by paracentesis. Contrarily, in patients with CHE ≥ 2.5 kU/L survival was significantly improved by TIPS as compared to treatment with paracentesis (P < 0.001). Conclusion: CHE is significantly associated with mortality and complications after TIPS insertion. Therefore, we suggest that CHE should be evaluated as an additional parameter for selecting patients for TIPS implantation.

In the 8 years since its introduction into clinical practice, initial enthusiasm for the transjugular intrahepatic portosystemic stent-shunt (TIPSS) has been tempered by a more critical appraisal of its role in the management of portal hypertension. TIPSS has established its role as a rescue procedure for variceal haemorrhage uncontrolled by endoscopic means and as a treatment for ectopic or recurrent variceal bleeding. Randomized trials comparing TIPSS with endoscopic methods in the secondary prophylaxis of oesophageal variceal haemorrhage have shown reduced rebleeding after TIPSS but no effect on survival. Its exact role in this situation awaits further assessment, including quality of life and cost analyses, and consideration of the current limited availability of the technique. Experience of TIPSS in patients with refractory ascites or hepatorenal syndrome has been disappointing. Little data currently exist, but results of further randomized studies comparing TIPSS with paracentesis for refractory ascites are awaited. Ideally these should be multicentre studies, and should include quality of life data for this poor prognostic group. Development of shunt insufficiency remains a major problem and occurs in approximately 50% patients at 1 year. The need for continued shunt surveillance by Doppler sonography and direct portography is the major limitation of TIPSS, but hopefully the development of covered stents will address this problem.

New tools for an old quest

BackgroundMultiparametric magnetic resonance imaging (MP-MRI) has high sensitivity for diagnosing breast cancers but cannot always be used as a routine diagnostic tool. The present study aimed to evaluate whether the diagnostic performance of perfluorobutane (PFB) contrast-enhanced ultrasound (CEUS) is similar to that of MP-MRI in breast cancer and whether combining the two methods would enhance diagnostic efficiency.Patients and methodsThis was a head-to-head, prospective, multicenter study. Patients with breast lesions diagnosed by US as Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 underwent both PFB-CEUS and MP-MRI scans. On-site operators and three reviewers categorized the BI-RADS of all lesions on two images. Logistic-bootstrap 1000-sample analysis and cross-validation were used to construct PFB-CEUS, MP-MRI, and hybrid (PFB-CEUS + MP-MRI) models to distinguish breast lesions.ResultsIn total, 179 women with 186 breast lesions were evaluated from 17 centers in China. The area under the receiver operating characteristic curve (AUC) for the PFB-CEUS model to diagnose breast cancer (0.89; 95% confidence interval [CI] 0.74, 0.97) was similar to that of the MP-MRI model (0.89; 95% CI 0.73, 0.97) (P = 0.85). The AUC of the hybrid model (0.92, 95% CI 0.77, 0.98) did not show a statistical advantage over the PFB-CEUS and MP-MRI models (P = 0.29 and 0.40, respectively). However, 90.3% false-positive and 66.7% false-negative results of PFB-CEUS radiologists and 90.5% false-positive and 42.8% false-negative results of MP-MRI radiologists could be corrected by the hybrid model. Three dynamic nomograms of PFB-CEUS, MP-MRI and hybrid models to diagnose breast cancer are freely available online.ConclusionsPFB-CEUS can be used in the differential diagnosis of breast cancer with comparable performance to MP-MRI and with less time consumption. Using PFB-CEUS and MP-MRI as joint diagnostics could further strengthen the diagnostic ability.Trial registration Clinicaltrials.gov; NCT04657328. Registered 26 September 2020.IRB number 2020-300 was approved in Chinese PLA General Hospital. Every patient signed a written informed consent form in each center.

Multiparametric MRI-Based Machine Learning Models for the Characterization of Cystic Renal Masses Compared to the Bosniak Classification, Version 2019: A Multicenter Study