The Neoangiogenic Transcriptomic Signature Impacts Hepatocellular Carcinoma Prognosis and Can Be Triggered by Transarterial Chemoembolization Treatment.

Background/Objectives: We evaluated the relationship between the neoangiogenic transcriptomic signature (nTS) and clinical symptoms, treatment outcomes, and survival in hepatocellular carcinoma (HCC) patients. Methods: This study prospectively followed 328 patients in the derivation and 256 in the validation cohort (with a median follow-up of 31 and 22 months, respectively). The nTS was associated with disease presentation, treatments administered, and overall survival rates. Additionally, this study investigated how multiple treatments influenced changes in nTS status and alterations in microRNA expression. Results: The nTS was identified in 27.4% of patients, linked to aggressive features like multifocality and elevated alpha-fetoprotein (AFP), a pattern consistent with that of the validation cohort. Most patients in both cohorts received treatment for HCC. nTS+ patients had limited access to, and benefited less from, liver transplantation or radiofrequency ablation (RFA) compared to nTS- patients. By the end, 78.9% had died, with nTS- patients showing better median survival and response to treatments than their nTS+ counterparts, who had lower survival across all treatment types. Among those who received transarterial chemoembolization (TACE), 31.2% (21/80 patients after the initial treatment and another four following a second TACE) transitioned from an nTS- to an nTS+ status. This shift was associated with lower survival and alterations in microRNA expressions related to oncogenic pathways. Conclusions: The nTS markedly influences treatment eligibility and survival in patients with HCC. Notably, the nTS can develop after repeated TACE procedures, significantly impacting patient survival and altering oncogenic microRNA expression patterns. These findings highlight the critical role of the nTS in guiding treatment decisions and prognostication in HCC management.

Transjugular Intrahepatic Portosystemic Shunt: Devices Evolution, Technical Tips and Future Perspectives.

Portal hypertension (PH) constitutes a pivotal factor in the progression of cirrhosis, giving rise to severe complications and a diminished survival rate. The transjugular intrahepatic portosystemic shunt (TIPS) procedure has undergone significant evolution, with advancements in stent technology assuming a central role in managing PH-related complications. This review aims to outline the progression of TIPS and emphasizes the significant influence of stent advancement on its effectiveness. Initially, the use of bare metal stents (BMSs) was limited due to frequent dysfunction. However, the advent of expanding polytetrafluoroethylene-covered stent grafts (ePTFE-SGs) heralded a transformative era, greatly enhancing patency rates. Further innovation culminated in the creation of ePTFE-SGs with controlled expansion, enabling precise adjustment of TIPS diameters. Comparative analyses demonstrated the superiority of ePTFE-SGs over BMSs, resulting in improved patency, fewer complications, and higher survival rates. Additional technical findings highlight the importance of central stent placement and adequate stent length, as well as the use of smaller calibers to reduce the risk of shunt-related complications. However, improving TIPS through technical means alone is inadequate for optimizing patient outcomes. An extensive understanding of hemodynamic, cardiac, and systemic factors is required to predict outcomes and tailor a personalized approach. Looking forward, the ongoing progress in SG technology, paired with the control of clinical factors that can impact outcomes, holds the promise of reshaping the management of PH-related complications in cirrhosis.

Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19.

This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.

MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal-maternal delivery outcomes in high-risk women.

OBJECTIVE: To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI. METHODS: 26 patients (mean age 36.24 y/o,SD 6.16) with clinical risk-factors and echographic suspicion of IP underwent 1.5 T-MRI. Two readers reviewed images. Gold-standard was histology in hysterectomised patients and obstetric evaluation at delivery for patients with preserved uterus. Accuracy and reproducibility of MRI findings were calculated. RESULTS: Incidence of IP was 50% (13/26) and of PP was 11.54% (3/26). MRI showed 100% sensitivity (95% CI = 75.3-100%) and 92.3% specificity (95% CI = 64.0-100%) in the diagnosis of IP. Gold-standard was histology in 10 cases and obstetric evaluation in 16. MRI findings with higher sensitivity were placental heterogeneity, uterine bulging and black intraplacental bands. Uterine scarring, placental heterogeneity, myometrial interruption and tenting of the bladder showed better specificity. MRI inter-rater agreement with Cohen's K was 1. 11 patients among 14 with MRI diagnosis of IP received IR assistance with positive impact on delivery outcomes in terms of blood loss, red cells count, intense care unit length of stay, days of hospitalisation and risk of being transfused. CONCLUSION: MRI is an accurate and reproducible technique in prenatal diagnosis of IP. MRI helps planning a safe and appropriate delivery eventually assisted by IR, which positively affects foetal and maternal outcomes. ADVANCES IN KNOWLEDGE: The adoption of MRI evaluation in patients with high risk of invasive placentation allows a more accurate diagnosis in terms of both presence of the disease and its extension to or through or even beyond the myometrium. This led to a better dedicated delivery management with eventual adoption of interventional radiology with a global positive effect on foetal and maternal outcomes.

A challenging case of pregnancy with placenta accreta and very rare irregular antibodies versus Cromer blood group system: a case report.

INTRODUCTION: This report describes the challenges of treating a pregnant woman who had a rare case of critical placenta accreta with concurrent Cromer system anti-Tc(a) and anti-Kidd A alloantibodies. No previous case of such alloimmunization in a patient with placenta accreta has been reported. CASE PRESENTATION: A 28-year-old African woman with anti-Cromer Tc(a) antibodies, anti-Kidd A antibodies and placenta accreta was admitted to the obstetric emergency department at our university hospital with persistent vaginal bleeding. Her rare Cromer blood group system antibodies had been diagnosed 1 month earlier; no compatible blood had been found despite a worldwide search. We performed a cesarean section after placement of Fogarty balloons in her uterine arteries with preoperative endovascular interventional radiology. Other therapeutic interventions included preoperative iron administration to raise hemoglobin and the scheduled predeposit of autologous blood. Intraoperative therapeutic management was aimed at preventing coagulopathy and massive bleeding. With the use of alternative medical techniques determined during perioperative planning, her intraoperative blood loss was only 1000 mL, despite the placenta accreta. She was discharged from the hospital 4 days after cesarean section. CONCLUSIONS: To the best of our knowledge, this is the first report of an alloimmunized patient with two different alloantibodies and concurrent high risk of bleeding because of placenta accreta. The close collaboration among obstetricians, anesthesiologists, interventional radiologists, blood bank pathologists and intensive care doctors prevented serious consequences in this patient. The exceptional feature of this case is the patient's double risk: the placenta accreta and the inability to transfuse compatible blood. These two extreme situations challenged the multidisciplinary medical team.