Breakthroughs and challenges in the management of pediatric viral hepatitis

Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) major causes of advanced liver disease and mortality worldwide. Although regarded as benign infections in children, their persistence through adulthood is undoubtedly of concern. Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment, which is currently far from being curative. Herein we describe direct-acting antivirals available for pediatric HCV (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) and their real-world use. A critical review of the HBV pediatric classification is provided. Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population, including capsid assembly modulators, antigen secretion inhibitors, silencing RNAs, and immune modifiers. Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.     

Rationale and design of the precise percutaneous coronary intervention plan (P3) study: Prospective evaluation of a virtual computed tomography‐based percutaneous intervention planner

IntroductionFractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) has been identified as a surrogate marker for vessel related adverse events. FFR can be derived from standard coronary computed tomography angiography (CTA). Moreover, the FFR derived from coronary CTA (FFR_CT) Planner is a tool that simulates PCI providing modeled FFR_CT values after stenosis opening.AimTo validate the accuracy of the FFR_CT Planner in predicting FFR after PCI with invasive FFR as a reference standard.MethodsProspective, international and multicenter study of patients with chronic coronary syndromes undergoing PCI. Patients will undergo coronary CTA with FFR_CT prior to PCI. Combined morphological and functional evaluations with motorized FFR hyperemic pullbacks, and optical coherence tomography (OCT) will be performed before and after PCI. The FFR_CT Planner will be applied by an independent core laboratory blinded to invasive data, replicating the invasive procedure. The primary objective is to assess the agreement between the predicted FFR_CT post‐PCI derived from the Planner and invasive FFR. A total of 127 patients will be included in the study.ResultsPatient enrollment started in February 2019. Until December 2020, 100 patients have been included. Mean age was 64.1 ± 9.03, 76% were males and 24% diabetics. The target vessels for PCI were LAD 83%, LCX 6%, and RCA 11%. The final results are expected in 2021.ConclusionThis study will determine the accuracy and precision of the FFR_CT Planner to predict post‐PCI FFR in patients with chronic coronary syndromes undergoing percutaneous revascularization.     

Angio-Based Fractional Flow Reserve,Functional Pattern of Coronary Artery Disease,and Prediction of Percutaneous Coronary Intervention Result: a Proof-of-Concept Study

Cardiovascular Drugs and Therapy - Wire-based coronary physiology pullback performed before percutaneous coronary intervention (PCI) discriminates coronary artery disease (CAD) distribution and...     

Lung magnetic resonance imaging in systemic sclerosis: a new promising approach to evaluate pulmonary involvement and progression

Clinical Rheumatology - Interstitial lung disease (ILD) is frequent and highly disabling in systemic sclerosis (SSc). Magnetic resonance imaging (MRI) is not routinely used to evaluate the lung,...     

KIT is dispensable for physiological organ vascularisation in the embryo

Blood vessels form vast networks in all vertebrate organs to sustain tissue growth, repair and homeostatic metabolism, but they also contribute to a range of diseases with neovascularisation. It is, therefore, important to define the molecular mechanisms that underpin blood vessel growth. The receptor tyrosine kinase KIT is required for the normal expansion of hematopoietic progenitors that arise during embryogenesis from hemogenic endothelium in the yolk sac and dorsal aorta. Additionally, KIT has been reported to be expressed in endothelial cells during embryonic brain vascularisation and has been implicated in pathological angiogenesis. However, it is neither known whether KIT expression is widespread in normal organ endothelium nor whether it promotes blood vessel growth in developing organs. Here, we have used single-cell analyses to show that KIT is expressed in endothelial cell subsets of several organs, both in the adult and in the developing embryo. Knockout mouse analyses revealed that KIT is dispensable for vascularisation of growing organs in the midgestation embryo, including the lung, liver and brain. By contrast, vascular changes emerged during late-stage embryogenesis in these organs from KIT-deficient embryos, concurrent with severe erythrocyte deficiency and growth retardation. These findings suggest that KIT is not required for developmental tissue vascularisation in physiological conditions, but that KIT deficiency causes foetal anaemia at late gestation and thereby pathological vascular remodelling.

     

Radiofrequency ablation vs surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria

BACKGROUNDSurgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria.AIMTo evaluate short- and long-term outcome in elderly patients (> 70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA.METHODSThe study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression.RESULTSAfter PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively (P = 0.001). Disease-free survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group (P = 0.001).Postoperative Clavien-Dindo III-IV complications were lower in the RFA group (1% vs 11%, P = 0.001) in association with a shorter length of stay (2 d vs 7 d, P = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (> 10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (> 1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (> 10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate.CONCLUSIONDespite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (> 70 years) with HCC in Milan criteria.