Pre-emptive TIPS in high-risk acute variceal bleeding. An updated and revised individual patient data meta-analysis.

BACKGROUND AND AIMS: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C<14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues. APPROACH AND RESULTS: We included all studies from the previous IPD-MA and searched for other possible eligible publications until September 2022. We performed a two-stage IPD-MA of data from 8 studies (4 randomized clinical trials and 4 observational). In addition, we performed a sensitivity analysis excluding those patients dying up to the first 72 hours after admission in the Drugs+Endoscopy arms of the 4 observational studies. The primary end point was the effects of p-TIPS versus Drugs+Endoscopy on 1-year survival.We identified 1389 patients (342 p-TIPS and 1047 Drugs+Endoscopy). The two-stage IPD-MA showed that p-TIPS significantly reduced the mortality in the overall population (HR=0·43, 95% CI: 0.32-0.60, p <0.001. This effect was observed in both subgroups of patients with Child-Pugh. The sensitivity analysis confirmed the survival benefit of p-TIPS. CONCLUSIONS: The updated two-stage IPD-MA confirms the significant survival advantage of p-TIPS in high-risk patients with cirrhosis and acute variceal bleeding. As a result, we recommend p-TIPS as the preferred first-choice treatment for these patients.

Comparison of HE4, CA125, ROMA and CPH-I for Preoperative Assessment of Adnexal Tumors.

(1) OBJECTIVE: To assess the performance of CA125, HE4, ROMA index and CPH-I index to preoperatively identify epithelial ovarian cancer (EOC) or metastatic cancer in the ovary (MCO). (2) METHODS: single center retrospective study, including women with a diagnosis of adnexal mass. We obtained the AUC, sensitivity, specificity and predictive values were of HE4, CA125, ROMA and CPH-I for the diagnosis of EOC and MCO. Subgroup analysis for women harboring adnexal masses with inconclusive diagnosis of malignancy by ultrasound features and Stage I EOC was performed. (3) RESULTS: 1071 patients were included, 852 (79.6%) presented benign/borderline tumors and 219 (20.4%) presented EOC/MCO. AUC for HE4 was higher than for CA125 (0.91 vs. 0.87). No differences were seen between AUC of ROMA and CPH-I, but they were both higher than HE4 AUC. None of the tumor markers alone achieved a sensitivity of 90%; HE4 was highly specific (93.5%). ROMA showed a sensitivity and specificity of 91.1% and 84.6% respectively, while CPH-I showed a sensitivity of 91.1% with 79.2% specificity. For patients with inconclusive diagnosis of malignancy by ultrasound features and with Stage I EOC, ROMA showed the best diagnostic performance (4) CONCLUSIONS: ROMA and CPH-I perform better than tumor markers alone to identify patients harboring EOC or MCO. They can be helpful to assess the risk of malignancy of adnexal masses, especially in cases where ultrasonographic diagnosis is challenging (stage I EOC, inconclusive diagnosis of malignancy by ultrasound features).

Risk of non-tumoural portal vein thrombosis in patients with HCV-induced cirrhosis after sustained virological response.

BACKGROUND & AIMS: Sustained virological response (SVR) to direct-acting antivirals ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analysed the long-term impact of SVR on the development of non-tumoural PVT. METHODS: Our study comprised of two well-characterized prospective cohorts (hepatitis C virus '(HCV)-Cured': n = 354/'HCV-Active': n = 179) of patients with HCV cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoural PVT and events known to modify its natural history (orthotopic liver transplantation, transjugular intrahepatic portosystemic shunt, death, tumoural PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis. RESULTS: Ten (2.8%) patients in the 'HCV-Cured' cohort developed a non-tumoural PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the 'HCV-Active' cohort were diagnosed with non-tumoural PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoural PVT development and stage A patients were at low risk. Importantly, HCV cure did not decrease the risk of non-tumoural PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio: 1.31 (95% confidence interval [95% CI]: 0.43-3.97); P = .635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 [95% CI: 0.287-0.715]; P < .001). CONCLUSIONS: The risk of non-tumoural PVT persists after HCV cure in patients with cirrhosis, despite improving survival. Even after aetiological cure, severity of liver disease remains the main determinant of non-tumoural PVT development.

External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial.

BACKGROUND: External trigeminal nerve stimulation (ETNS) is an emergent, non-invasive neurostimulation therapy delivered bilaterally with adhesive skin electrodes. In previous studies, ETNS was associated to a decrease in seizure frequency in patients with focal drug-resistant epilepsy (DRE). OBJECTIVE: To determine the long-term efficacy and tolerability of ETNS in patients with focal DRE. Moreover, to explore whether its efficacy depends on the epileptogenic zone (frontal or temporal), and its impact on mood, cognitive function, quality of life, and trigeminal nerve excitability. METHODS: Forty consecutive patients with frontal or temporal DRE, unsuitable for surgery, were randomized to ETNS or usual medical treatment. Participants were evaluated at 3, 6 and 12 months for efficacy, side effects, mood scales, neuropsychological tests and trigeminal nerve excitability. RESULTS: Subjects had a median of 15 seizures per month and had tried a median of 12.5 antiepileptic drugs. At 12 months, percentage of responders was 50% in ETNS group and 0% in control group. Seizure frequency in ETNS group decreased by -43.5% from baseline. Temporal epilepsy subgroup responded better than frontal epilepsy subgroup (55.56% vs. 45.45%, respectively). Median stimulation intensity was 6.2 mA. ETNS improved quality of life, but not anxiety or depression. Long-term ETNS affected neither neuropsychological function, nor trigeminal nerve excitability. No relevant adverse events were observed. CONCLUSIONS: ETNS is an effective and well-tolerated therapy for focal DRE. Patients with temporal epilepsy showed a better response than those with frontal epilepsy. Future studies with larger populations may define its role compared to other neurostimulation techniques. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that ETNS reduces seizure frequency in patients with focal DRE.