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

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

Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study

In HCC, tumor microenvironment, heavily influenced by the underlying chronic liver disease, etiology and stage of the tissue damage, affects tumor progression and determines the high heterogeneity of the tumor. Aim of this study was to identify the circulating and tissue components of the microenvironment immune-mediated response affecting the aggressiveness and the ensuing clinical outcome. We analyzed the baseline paired HCC and the surrounding tissue biopsies from a prospective cohort of 132 patients at the first diagnosis of HCC for immunolocalization of PD-1/PD-L1, FoxP3, E-cadherin, CLEC2 and for a panel of 82 microRNA associated with regulation of angiogenesis, cell proliferation, cell signaling, immune control and autophagy. Original microarray data were also explored. Serum samples were analyzed for a panel of 19 cytokines. Data were associated with biochemical data, histopathology and survival. Patients with a more aggressive disease and shorter survival, who we named fast-growing accordingly to the tumor doubling time, at presentation had significantly higher AFP levels, TGF-β1 and Cyphra 21-1 levels. Transcriptomic analysis evidenced a significant downregulation of CLEC2 and upregulation of several metalloproteinases. A marked local upregulation of both PD-1 and PD-L1, a concomitant FoxP3-positive lymphocytic infiltrate, a loss of E-cadherin, gain of epithelial-mesenchymal transition (EMT) phenotype and extreme poor differentiation at histology were also present. Upregulated microRNA in fast-growing HCCs are associated with TGF-β signaling, angiogenesis and inflammation. Our data show that fast HCCs are characterized not only by redundant neo-angiogenesis but also by unique features of distinctively immunosuppressed microenvironment, prominent EMT, and clear-cut activation of TGFβ1 signaling in a general background of long-standing and permanent inflammatory state

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

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Cardiopulmonary hemodynamics and c-reactive protein as prognostic indicators in compensated and decompensated cirrhosis

The main stages of cirrhosis (compensated and decompensated) have been substaged based on clinical, endoscopic, and portal pressure (determined by the hepatic venous pressure gradient, HVPG) features. Vasodilatation leading to a hyperdynamic circulatory state is central in the development of a late decompensated stage with inflammation being currently considered a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation (by C reactive protein, CRP) among the different substages of cirrhosis and to investigate their interrelationship and prognostic relevance

Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy

Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management

Mortality after transjugular intrahepatic portosystemic shunt in older adult cirrhotic patients: a validated prediction model

none34Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in cirrhotic patients with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (≥70 years) is debated and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults.Vizzutti, Francesco; Celsa, Ciro; Calvaruso, Vincenza; Enea, Marco; Battaglia, Salvatore; Turco, Laura; Senzolo, Marco; Nardelli, Silvia; Miraglia, Roberto; Roccarina, Davide; Campani, Claudia; Saltini, Dario; Caporali, Cristian; Indulti, Federica; Gitto, Stefano; Zanetto, Alberto; Di Maria, Gabriele; Bianchini, Marcello; Pecchini, Maddalena; Aspite, Silvia; Di Bonaventura, Chiara; Citone, Michele; Guasconi, Tomas; Di Benedetto, Fabrizio; Arena, Umberto; Fanelli, Fabrizio; Maruzzelli, Luigi; Riggio, Oliviero; Burra, Patrizia; Colecchia, Antonio; Villa, Erica; Marra, Fabio; Cammà, Calogero; Schepis, FilippoVizzutti, Francesco; Celsa, Ciro; Calvaruso, Vincenza; Enea, Marco; Battaglia, Salvatore; Turco, Laura; Senzolo, Marco; Nardelli, Silvia; Miraglia, Roberto; Roccarina, Davide; Campani, Claudia; Saltini, Dario; Caporali, Cristian; Indulti, Federica; Gitto, Stefano; Zanetto, Alberto; Di Maria, Gabriele; Bianchini, Marcello; Pecchini, Maddalena; Aspite, Silvia; Di Bonaventura, Chiara; Citone, Michele; Guasconi, Tomas; Di Benedetto, Fabrizio; Arena, Umberto; Fanelli, Fabrizio; Maruzzelli, Luigi; Riggio, Oliviero; Burra, Patrizia; Colecchia, Antonio; Villa, Erica; Marra, Fabio; Cammà, Calogero; Schepis, Filipp