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The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients. Between 2008 and 2020, among 774 C-P B patients with aHCC not amenable/responsive to locoregional treatments, 410 underwent sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors. In the unmatched population, median OS was 9.7 months in patients treated with sorafenib, 8.0 with MC, and 3.9 months with BSC. In sorafenib vs. BSC-matched patients (135 couples), median OS was 7.3 (4.9–9.6) vs. 3.9 (2.6–5.2) months (p <0.001). ECOG-Performance Status, tumor size, macrovascular invasion, AFP, treatment-naive, and sorafenib were independent predictors of survival. In MC vs. BSC-matched patients (40 couples), median OS was 9.0 (0.2–17.8) vs.3.0 (2.2–3.8) months (p <0.001). Median OS did not differ (p = 0.283) in sorafenib vs. MC-matched patients (55 couples). C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis. [ABSTRACT FROM AUTHOR]

The benefits of immunonutrition in patients who underwent major abdominal surgery have been recently established, but the optimal combination of immunonutrients has remained unclear. The aim is to clarify this point. A systematic search of randomized clinical trials about immunonutrition in major abdominal surgery was made. A frequentist random-effects component network meta-analysis was conducted, reporting the P score and odds ratio or mean difference with a 95% confidence interval. The best components and best plausible strategies were described. The critical endpoints were morbidity and mortality rates. The important endpoints were infectious complication rate and length of stay. The meta-analysis includes 87 studies and 8,375 patients. The best approach for morbidity rate, with a moderate grade of certainty, was the use of perioperative enteral/oral immunonutrition with arginine, glutamine, and polyunsaturated fatty acids (odds ratio 0.32; 0.10 to 0.98; P score of 0.93). The mortality rate was reduced by postoperative enteral immunonutrition with RNA, arginine, and polyunsaturated fatty acids (odds ratio 59; 0.29 to 1.22; P score 0.84) but with a low grade of certainty. No significant heterogeneity or incoherence is observed. The length of stay and infectious results are "at risk" for high heterogeneity or network meta-analysis incoherence. The component analysis confirmed that postoperative oral/enteral use of 2 or 3 components is crucial to reducing morbidity rate. The oral/enteral immunonutrition in the postoperative period, with multiple immunonutrients, can reduce the morbidity rate in patients undergoing major abdominal surgery. The effect of immunonutrition on mortality, infectious disease, and length of stay is unclear. [ABSTRACT FROM AUTHOR]

Our knowledge of monochorionic pregnancies' complications is largely based on the extensive ongoing research on monochorionic placental structure. Previous studies on the concordance of umbilical cord insertions are limited. This study aimed to evaluate placental anastomoses and cord insertions as independent risk factors for neonatal adverse outcomes. This was a prospective study conducted at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy from April 2021 to December 2022. Seventy-six women with a monochorionic pregnancy were enrolled at their first-trimester scan. After delivery, all placentas that were confirmed to be monochorionic were analyzed according to standard protocols, including those of complicated monochorionic twin pregnancies. The primary outcomes were a Composite Monochorionic Pregnancy Outcome (CMPO) and a Composite Neonatal Adverse Outcome (CNAO). The secondary outcome was the birth weight discordance between the neonates. The CMPO occurred in 15.8 % pregnancies, and the CNAO occurred in 67.1 % pregnancies. The analysis confirmed a significant association between velamentous cord insertions and neonatal adverse events (p = 0.003). Also, a significant positive association (p = 0.0326) between twin birth weight discordance and discordance in twins umbilical cord insertions' sites was found. No significant association between the number and type of the anastomoses and both the CMPO or CNAO was detected. Our data suggest that the routine sonographic assessment of umbilical cords' insertion sites during the first trimester could be helpful in predicting fetal and neonatal adverse events. We believe that this sonographic assessment should start to be implemented in our routine care of monochorionic pregnancies. [Display omitted] • Velamentous insertions are significantly associated with neonatal adverse events. • Twin cord insertions are classified in concordant, intermediate, discordant. • Twin weight discordance increases with discordance in umbilical cord insertions. • Sonographic assessment of umbilical cords could predict neonatal adverse events. [ABSTRACT FROM AUTHOR]

Left ventricular ejection fraction-based arrhythmic risk stratification in nonischemic cardiomyopathy (NICM) is insufficient and has led to the failure of primary prevention implantable cardioverter defibrillator trials, mainly due to the inability of selecting patients at high risk for sudden cardiac death (SCD). Cardiac magnetic resonance offers unique opportunities for tissue characterization and has gained a central role in arrhythmic risk stratification in NICM. The presence of myocardial scar, denoted by late gadolinium enhancement, is a significant, independent, and strong predictor of ventricular arrhythmias and SCD with high negative predictive value. T1 maps and extracellular volume fraction, which are able to quantify diffuse fibrosis, hold promise as complementary tools but need confirmatory results from large studies. [ABSTRACT FROM AUTHOR]

The novel AGREE classification for adverse events (AEs) in gastrointestinal (GI) endoscopy has not yet been validated in a real-world setting. Our study aims to evaluate the correlation between the grades of AEs in the ASGE and AGREE classifications and to assess the interobserver agreement of the two classification systems. The correlation and association between the AE grades of the ASGE and AGREE classifications were analyzed using the Spearman rank correlation test and the chi-squared analysis, respectively. A weighted Cohen's kappa coefficient analysis was performed to determine the interobserver agreement of both classification systems. We prospectively collected the AEs that occurred in our endoscopy unit over the past five years. A total of 226 AEs (226/84,863, 0.3%) occurred. There was a correlation between the ASGE and AGREE classifications (ρ = 0.61) and a moderately significant association (p < 0.01, Cramer's V = 0.7). The interobserver agreement for the ASGE classification was fair (kappa 0.60, 95% confidence interval [CI]: 0.54, 0.67), whereas it was good for the AGREE classification (kappa 0.80, 95% CI: 0.62, 0.87). The AGREE classification was validated for the first time in a real-world setting and showed a positive correlation and higher interobserver agreement than the ASGE classification. [ABSTRACT FROM AUTHOR]

Migrants from Africa are vulnerable to viral infections during their journey. Migrants who arrived in western Sicily were offered early screening for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection. A questionnaire was administered to evaluate risk factors, and antiviral therapy was offered to subjects with active infection. A multiple regression analysis and adjusted odds ratio were obtained to evaluate risk factors. Overall, 2,639 of 2,751 (95.9%) migrants who arrived between 2015 and 2017 accepted screening and 1,911 (72.4%) completed the questionnaire. HBsAg was positive in 257 (9.7%) migrants, 24 (0.9%) were anti-HCV positive and 57 (2.2%) had HIV infection. The prevalence of HBV infection was higher in women (aOR 2.47,95%CI 1.90–3.20), p = 0.003) and in people who endured physical and/or sexual violence (aOR 2.24,95%CI 1.87–3.55, p <0.001), while HIV infection was more frequent in women (aOR 5.40,95%CI 3.09–9.43, p <0.001) who were in Libya for a long period (aOR 5.66,95%CI 2.90–10.70, p = 0.004) and endured physical and/or sexual violence (aOR 14.77,95%CI 8.34–22.11, p <0.001). Being older than 18 was associated with HCV infection (p <0.001). Overall, 77% of 57 subjects with HIV infection were retained in care, 79% of 70 chronic HBV hepatitis cases started nucleot(s)ide analogues and 61% of 18 HCV-RNA positive cases received direct-acting antiviral therapy. These findings evidence the effectiveness and feasibility of infectious disease screening programs for migrants. [ABSTRACT FROM AUTHOR]

A PWID man, HCV/HBV-HDV/HIV-infected, underwent liver transplantation (LT) for HCC in 2012 at the age of 52 years. HCC tissue showed high HDV-RNA (88,400 copies/cell), low total HBV-DNA (0.00001 c/c), and HBVcccDNA0.00008 c/c), without detectable HBV-RNA. High-throughput HBV integration sequencing (HBIS) identified 657 HBV integration sites.HBV integrants were predominantly represented by HBx gene sequences. After LT, Tacrolimus, Bictegravir/Emtricitabine/TAF, and anti-HBs immunoglobulin were administered, yielding HBsAg, HDV-RNA, and HCV-RNA negativity. In 2018, HBsAg reversion was observed with undetectable HBV-DNA and HDV-RNA >19,000 c/ml. In 2019, HDV-related hepatitis occurred. Intrahepatic HBcAg, HBsAgHBV DNA, HBVcccDNA, and HBV-RNA were undetectable. HDV RNA concentrations were very high in the liver (3,920,000 c/c) but low in the serum (214 IU/mL). CT scan (CTs) suspected an isolated HCC recurrence in the left adrenal gland, confirmed by adrenalectomy. Real-time PCR in the tumor from the adrenal gland revealed high levels of HDV RNA (5.5 c/c) but low levels of HBV DNA (0.00009 c/c) and HBVcccDNA (0.00001 c/c). HBV RNA was undetectable. HBIS identified 3497 HBV integrations, most of which included HBs gene sequences. After adrenalectomy, HBsAg and HDV-RNA became undetectable. Anti-HBs immunoglobulin was continued with Everolimus. In 2021, CTs showed two HCC nodules in the liver and one in the right adrenal gland. TACE was performed, and TKI therapy was started. In 2023, new HDV hepatitis occurred, with HDV-RNA>3,631,360 UI/ml and HBV-DNA <10UI/ml. For the progression of HCC, RFA on the right adrenal gland was performed, and Bulevirtide was started. After 3 months, HDV-RNA was 48,638 c/ml, and transaminases were normal. This case demonstrates HDV replication in extrahepatic HCC recurrence, despite low levels of HBVcccDNA. The decreased HDV RNA levels after RFA and BLV therapy suggest that HCC metastases may serve as HBsAg production sites following HBV integration. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a hypertensive disorder of pregnancy that can cause severe complications and adverse fetal/maternal outcomes. We aimed to estimate the annual economic impact of incorporating Elecsys® sFlt-1/PlGF PE ratio, which measures soluble fms-like tyrosine kinase-1 and placental growth factor, into routine clinical practice in Argentina to aid diagnosis of PE and hemolysis, elevated liver enzymes, and low platelets syndrome from second trimester onward in pregnancies with clinical suspicion of PE. A decision tree was used to estimate annual economic impact on the Argentine health system as a whole, including relevant costs associated with diagnosis, follow-up, and treatment from initial presentation of clinically suspected PE to delivery. Annual costs of a standard-of-care scenario and a scenario including PE ratio (reference year 2021) were analyzed. The economic model estimated that using the sFlt-1/PlGF ratio would enable the overall health system to save ∼$6987 million Argentine pesos annually (95% confidence interval $12 045-$2952 million), a 39.1% reduction in costs versus standard of care, mainly due to reduced hospitalizations of women with suspected PE. The economic impact calculation estimated net annual savings of approximately $80 504 Argentine pesos per patient with suspected PE. Based on the assumed uncertainty of the parameters, the likelihood the intervention would be cost saving was 100% for the considered scenarios. Our analysis suggests that the implementation of the sFlt-1/PlGF ratio in women with suspected PE in Argentina will enable the health system to achieve significant savings, contributing to more efficient clinical management through the likely reduction of unnecessary hospitalizations, depending on assumptions. Results rest on the payers' ability to recover savings generated by the intervention. • The implementation of the soluble fms-like tyrosine kinase-1/placental growth factor ratio in women with suspected preeclampsia in Argentina will enable the health system to achieve significant savings. • This is the first economic assessment to analyze the impact of the implementation of the soluble fms-like tyrosine kinase-1/placental growth factor ratio in the Argentine health system. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to quantify the histological improvement and its risk factors in patients with NASH enrolled in the placebo arms of randomized controlled trials (RCTs), and to indirectly compare the effect of several investigational drugs for NASH on validated histological outcomes.Data Synthesis: A comprehensive search was conducted to detect phase 2 and 3 RCTs comparing pharmacological interventions in patients with NASH. According to Food and Drug Administration (FDA) recommendations, primary outcomes included: 1) NASH resolution without worsening of fibrosis; 2) At least 1-point reduction in fibrosis without worsening of NASH. Meta-analysis and meta-regressions were conducted on placebo arms, while network meta-analysis was performed on intervention arms. A total of 15 RCTs met the eligibility criteria. The meta-analysis on placebo arms showed a pooled estimate rate of 17% (95%C.I. 12%-23%;I2 = 86%; p < 0.01) for NASH resolution without worsening of fibrosis and of 21% (95%C.I. 13%-31%;I2 = 84%; p < 0.01) for ≥1stage improvement of fibrosis without worsening of NASH. Phase 3 (vs Phase 2)RCTs, older age and higher AST levels were significantly associated with progression of liver disease by univariate meta-regression. At network meta-analysis, Semaglutide (P-score 0.906), Pioglitazione alone (score 0.890) and plus Vitamin E (0.826) had the highest probability of being ranked the most effective intervention for NASH resolution without worsening of fibrosis, while Aldafermin (0.776), Lanifibranor (0.773) and Obeticholic acid (0.771) had the highest probability to achieve ≥1 stage of fibrosis improvement without worsening of NASH.Conclusion: This study confirms the heterogeneity of histological progression of untreated patients with NASH and provides evidence to stratify patients according to identified risk factors in future RCTs of combination therapies. PROSPERO CRD42021287205. [ABSTRACT FROM AUTHOR]

The epidemiology of liver cirrhosis is evolving and the etiology, complications, and comorbidities of cirrhosis are continuously changing, presenting new challenges. We reported data from an observational, monocentric study including 1,617 patients with liver cirrhosis admitted to our liver unit from January 2014 to December 2023. The mean age of patients was 66.8 years, with a male predominance except for autoimmune etiology. During the observation period, the number of hospitalized patients with active HCV infection decreased from 47.9% in 2014 to 9.2% in 2023, while patients with HCV cirrhosis in sustained virologic response (SVR) increased from 15.6% in 2014 to 26.2% in 2023. Hospitalizations for HBV-related cirrhosis remained stable (5.5% in 2014 and 8.5% in 2023. Patients for alcohol-related cirrhosis increased from 16.6% in 2014 to 23.9% 2023 and patients with metabolic cirrhosis increased from 10.6% in 2014 to 36.8% in 2023. The rate of patients with autoimmune cirrhosis (3.0% in 2014 and 4.2% in 2023) and cryptogenic cirrhosis (6.0% in 2014 to 7.9% in 2023) remained stable over the years. Patients with alcohol-related cirrhosis (mean age 59.5 years), HBV cirrhosis (62.1 years) and autoimmune etiologies (62.2 years) were younger than patients with HCV cirrhosis (69.3 years), metabolic cirrhosis (68.3 years) and cryptogenic cirrhosis (67.6 years). The most frequent complication for hospitalization was HCC in active (47.8%) and SVR (58.2%) HCV cirrhosis, and in HBV cirrhosis (47.3%), with the ascites was more frequent in alcohol-related (45.8%) and metabolic (34.1%) cirrhosis Patients with metabolic cirrhosis had the most extrahepatic comorbidities (66.3% diabetic, 18.0% chronic kidney disease, and 20.7% heart disease). Liver cirrhosis epidemiology is changing, with decreasing HCV infections but increasing alcohol-related and metabolic cases. Complications and comorbidities require tailored management strategies. Effective public health interventions and adaptive healthcare approaches are crucial to address these evolving challenges. [ABSTRACT FROM AUTHOR]

Direct Acting Antivirals(DAAs) achieve the highest rate of sustained viral response(SVR) in patients with genotype-1b(G1b) Hepatitis C virus(HCV) infection. Reducing treatment duration can simplify the management and improve adherence of therapy. The study evaluates the efficacy of 8 weeks of elbasvir/grazoprevir regimen in 75 treatment-naïve(TN), G1b patients with mild-moderate fibrosis(Liver Stiffness by Fibroscan® <9.0 kPa). Viral load(VL) has been evaluated by Roche TaqMan RT-PCR(LLOQ<15 IU/ml). Mean age was 61.0 ± 14.2 years, 44% were male, mean LS by Fibroscan® was 6.1 ± 1.8 kPa. Twenty-eight patients(37.3%) had an HOMA>2.5. Two patients were excluded from analysis(one dropped out and the other one had diagnosed genotype 2c at genotyping by sequencing performed after relapse). At 8 weeks(EOT), 71 out of 73 patients(97.3%) had undetectable HCV-RNA, while in two cases HCV-RNA was detectable but with VL<15 IU/ml. Both of them achieved SVR. Two G1b patients relapsed at 12 weeks of follow-up, both with baseline VL>800,000 IU/ml and HOMA score 1.3 and 3.8 respectively. Both had undetectable HCV VL at 4th week and at the EOT. Modified intention-to-treat SVR12 for G1b patients was 71/73(97.3%). In naïve, genotype-1b HCV-infected patients with mild/moderate liver fibrosis, short course of 8 weeks of EBR/GZR appears to achieve high efficacy regardless of features of insulin resistance. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence of cardiac device-related infection (CDRI) among patients with cardiac device (CD) during late-onset bloodstream infection (BSI) and to identify the risk factors associated with CDRI.Methods: Patients with a CD (cardiac implantable electronic devices -CIED- and/or prosthetic heart valve -PHV-) and late-onset-BSI (>1 year after the CD implantation/last manipulation) were selected from the PROBAC project, a prospective, observational cohort study including adult patients with bacteraemia consecutively admitted to 26 Spanish hospitals from October 2016 to March 2017. Multivariate analyses using logistic regression were performed to identify the risk factors associated with CDRI.Results: 317 BSI from patients carrying a CD were registered, 187 (56.2%) were late-onset-BSI. A total of 40 (21.4%) CDRI were identified during late-onset-BSI. The CDRI cumulative incidence in Gram-positive-BSI was 41.8% (38/91), with S. aureus, Enterococcus spp. and viridans streptococci showing the greatest percentages: 40% (12/30), 42% (11/26) and 75% (6/8), respectively. Independent predictors of CDRI were an unknown source of infection (OR: 2.88 [CI 95%:1.18-7.06], p = 0.02), Gram-positive-aetiology (23.1 [5.23-102.1], p < 0.001) and persistent bacteraemia (4.81 [1.21-19], p = 0.03). In an exploratory analysis, S. aureus (3.99 [1.37-11.65], p = 0.011), Enterococcus spp. (5.21 [1.76-15.4], p = 0.003) and viridans streptococci (28.7 [4.71-173.5], p < 0.001) aetiology were also found to be risk factors for CDRI.Conclusions: CDRI during late-onset-BSI is a frequent phenomenon. Risk of CDRI differs among species, happening in almost half of the Gram-positive-BSI. An unknown source of the primary infection, Gram-positive-aetiology -especially S. aureus, Enterococcus spp. and viridans streptococci-, and persistent bacteraemia were identified as risk factors for CDRI. [ABSTRACT FROM AUTHOR]

Background: To evaluate the association between sex and ventricular arrhythmias (VA) or sudden death (SD) in nonischemic dilated cardiomyopathy, including analysis of potential confounders.Methods and Results: Retrospective cohort study of consecutive patients with DCM referred for cardiac magnetic resonance at 2 tertiary hospitals. The primary combined end point encompassed sustained VA, appropriate implantable cardioverter defibrillator therapies, resuscitated cardiac arrest, and SD. We included 1165 patients with median follow-up of 36 months (interquartile range 20-58 months). The majority of patients (66%) were males. Males and females had similar left ventricular ejection fraction, but the prevalence of late gadolinium enhancement (LGE) at cardiac magnetic resonance was significantly higher among males (48% vs 30%, P < .001). Males had higher cumulative incidence of the primary end point (8% vs 4%, P = .02), and male sex was a significant predictor of the primary end point at univariate analysis (hazard ratio 1.93, P = .02). However, LGE had a major confounding effect in the association between sex and the primary outcome: the hazard ratio of male sex adjusted for LGE was 1.29 (P = .37). LGE+ females had significantly higher cumulative incidence of the primary end point than LGE- males (13% vs 1.8%, P < .001).Conclusions: In patients with DCM, the prevalence of LGE is significantly higher among males, implying a major confounding effect in the association between male sex and VA or SD. LGE+ females have significantly higher risk than LGE- males. These data do not support the inclusion of sex into risk stratification algorithms for VA or SD in DCM. [ABSTRACT FROM AUTHOR]

An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics. [ABSTRACT FROM AUTHOR]

Concern regarding suboptimal cure rates has led to some endocrine surgery units abandoning focused parathyroidectomy for primary hyperparathyroidism in favor of open bilateral neck exploration or making intraoperative parathyroid hormone estimation mandatory in focused parathyroidectomy. This study explores whether focused parathyroidectomy for radiologically localized primary hyperparathyroidism without intraoperative parathyroid hormone is still a valid approach. Retrospective review of a tertiary referral endocrine surgery unit database. All parathyroidectomies for primary hyperparathyroidism over 6 years (2013–2019) were included. Lithium-induced hyperparathyroidism, reoperations, familial disease, and concurrent thyroid surgery were excluded. Characteristics and outcomes for focused parathyroidectomy and open bilateral neck exploration were compared by intention-to-treat and treatment delivered. Persistence and recurrence, conversions and complications were analyzed as endpoints. A total of 2,828 parathyroidectomies were performed and 2,421 analyzed. By intention to treat there were 1,409 focused parathyroidectomies and 1,012 open bilateral neck explorations. Focused parathyroidectomy patients were younger: 63 vs 66 years (P <.01); however, gender (77%, 79% female), preoperative peak serum calcium (2.72, 2.70 mmol/L [ P =.23]), and serum parathyroid hormone (11.5, 11.0 pmol/L [ P =.52]) did not differ. In total, 229 (16.3%) focused parathyroidectomies were converted to open bilateral neck exploration. Multiple gland disease was confirmed in 54.5% of converted patients. Median follow-up was 41 months (3–60 months). Persistence or recurrence requiring reoperation totaled 2.2% and did not differ between focused parathyroidectomy and open bilateral neck exploration in either intention to treat or final treatment analyses. Complications occurred in 1.2% of focused parathyroidectomy and 3.2% open bilateral neck exploration (P <.01). In experienced hands and with a ready-selective approach to conversion, focused parathyroidectomy based on concordant imaging and without intraoperative parathyroid hormone may deliver equivalent cure rates to open bilateral neck exploration with significantly fewer complications. Focused parathyroidectomy without intraoperative parathyroid hormone should therefore be maintained in the endocrine surgeon's armamentarium. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (CHC) is associated with hepatic steatosis, related to both a direct viral action and metabolic features. Vice-versa data on hepatic steatosis after viral eradication by direct-acting antiviral agents (DAA) are undefined although the presence of metabolic alterations could strongly influence the occurrence of steatosis as in NAFLD. The controlled attenuation parameter (CAP) (FibroscanⓇ) allows the qualitative and quantitative evaluation of fatty liver. to evaluate in patients with CHC whether hepatic steatosis diagnosed by CAP modifies after DAAs-induced sustained virologic response (SVR). Data were collected the day of DAAs therapy starting and six months after SVR. CAP ≥ 248 dB/m defined the presence of steatosis. 794 CHC SVR patients referring to 2 Italian Units were enrolled. Mean age was 64 ± 16 ys, 50% males, BMI 25.4 ± 4 kg/m2, genotype type-1 in 73%, type-3 in 8%. Prevalence of hepatic steatosis at baseline was 32% by US and 46% by CAP. De novo steatosis developed in 125 (29%), resolution in 122 (30%). At multivariate analysis de novo steatosis was independently associated with male sex (OR 1.7, CI 95% 1.09–2.67; p = 0.02) and baseline BMI (for unit increase OR 1.19, CI 95%1.11–1.29; p < 0.001). Baseline BMI (for unit increase OR 0.47, CI 95% 0.25–0.89; p = 0.02) and triglycerides (for unit increase OR 0.93, CI 95% 0.87–0.99; p = 0.03) prevented steatosis resolution after therapy. after SVR de novo steatosis and resolution of baseline steatosis are closely related to the presence of metabolic comorbidities. [ABSTRACT FROM AUTHOR]

Routine screening of the spine for vertebral fracture is recommended in the recent international standards of care for boys with Duchenne muscular dystrophy (DMD). Recent international consensus endorses the use of dual energy absorptiometry vertebral fracture assessment for identification of vertebral fractures in children, which could be used instead of spine radiographs. This study aims to evaluate the inter-observer agreement for vertebral fracture classification in boys with DMD, and the impact on clinical management. Dual energy absorptiometry vertebral fracture assessment and morphometric analysis in 39 boys was performed by a reader with no prior experience (R1) and 2 readers with experience (R2 and R3). Inter-observer concordance of vertebral fracture grading comparing R1 with R2 and R3 was substantial (Kappa 0.66, 95% CI 0.56, 0.76). Concordance between R2 and R3 was almost perfect (Kappa 0.93, 95% CI 0.89, 0.97) which did not lead to differences in clinical management. Grading by R1 in comparison to R2 and R3 would have led to change in management of 5/39 boys (13%), according to recent standards of care guidance. Structured education programme on identification of vertebral fractures should be explored to ensure consistency of reporting of this important health outcome measure in DMD. [ABSTRACT FROM AUTHOR]

Background: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings.Aim: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital.Methods: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods.Findings: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response.Conclusion: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment. [ABSTRACT FROM AUTHOR]

Aortic coarctation (COA) is frequent congenital heart disease. It can be difficult to assess the indication for intervention or re-intervention in some cases. Exercise stress echocardiography (ESE) can be helpful for hemodynamic evaluation in patients with COA or reCOA. We aimed to determine ESE parameters predictive of intervention (angioplasty or surgery). We retrospectively reviewed 94 ESE performed in children (n = 14) and adults with native or repaired CoA and unclear indication for intervention in three centers in France. Exercise test was performed concomitantly to echocardiography on the e-bike in semi-lying position. The protocol was adapted according to the age and the physical condition. Echocardiography protocol included left ventricular adaptation (LVA) to effort and peak systolic gradient (PSG) at isthmus and appearance of diastolic tail during effort. We investigated risk marker associated with subsequent indication for intervention. Median age (min–max) was 26 years (10–72). Intervention was subsequently performed in thirteen patients (14.7%). Fifty-six patients (60.2%) had simple COA and 37 (39.8%) had complex anatomy, 24 (25%) had hypertension. Poor LVA was present in 13 (14%). Diastolic tail during effort appeared in 65 cases. The mean pic isthmus gradient 50 ± 21 mmHg (min: 15; max: 124). Poor LVA was associated with more interventions (log-rank, P = 0.004) (Fig. 1). On univariate analysis presence of antihypertensive drugs (HR: 4.13, 95% CI [1.35–12.65]; P = 0.013), systolic blood pressure at rest (HR: 1.04, 95% CI [1.011–1.072]; P = 0.007); the lower exercise power (Watts) (HR: 0.98; 95% CI [0.96–0.99]; P = 0.001); poor LVA (HR: 5.95, 95% CI [1.56–22.65]; P = 0.009); peak systolic gradient at rest and on effort at isthmus (HR: 1.06, 95% CI [1.03–1.10] and HR: 1.04, 95% CI [1.02–1.06]) were significantly predictive of interventions (Table 1). ESE is a useful tool for hemodynamic evaluation of COA. More severe forms that needed intervention showed less well adaption of the LV to effort and increase in the cardiac output and afterload. [ABSTRACT FROM AUTHOR]

Sorafenib is the gold standard therapy for the advanced hepatocellular carcinoma (HCC). No scoring/staging is universally accepted to predict the survival of these patients. To evaluate the accuracy of the available prognostic models for HCC to predict the survival of advanced HCC patients treated with Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. The performance of several prognostic scores was assessed through a Cox regression-model evaluating the C-index and the Akaike Information Criterion (AIC). Data of 1129 patients were analyzed. The mean age of patients was 61.6 years, and 80.8% were male. During a median follow-up period of 13 months, 789 patients died. The median period of Sorafenib administration was 4 months. All the prognostic scores were able to predict the overall survival (p <0.001) at univariate analysis, except the Albumin-Bilirubin score. The Italian Liver Cancer score (CLIP) yielded the highest accuracy (C-index 0.604, AIC 9898), followed by the ITA.LI.CA. prognostic score (C-index 0.599, AIC 9915). The CLIP score had the highest accuracy in predicting the overall survival of HCC patients treated with Sorafenib, although its performance remained poor. Further studies are needed to refine the current ability to predict the outcome of HCC patients undergoing Sorafenib. [ABSTRACT FROM AUTHOR]

To investigate whether the decrease in dyspnea in neuromuscular diseases after air stacking (AS) occurs mostly in patients with decreased inspiratory muscle force and ensuing chest wall restriction or heterogeneous ventilation across the lungs. Interventional, before-after study. A neurorehabilitation inpatient and outpatient center. Fifteen consecutive adult patients affected by neuromuscular diseases (N=15). AS treatment. Patients had vital capacity (VC) and sniff nasal inspiratory pressure (SNIP) measured. We measured Borg score, oxygen saturation, and ventilation heterogeneity across the lung as estimated from the difference between respiratory resistance at 5 and 19 Hz (R 5-19) with the forced oscillation technique before and 5, 30, 60, and 120 minutes after applying AS. Before AS, Borg score was significantly related to R 5-19 (r 2 0.46, P <.05) but not to VC % predicted, SNIP % predicted, and time since symptom onset. After AS, average Borg score gradually decreased (P =.005), whereas inspiratory flow resistance at 5 Hz, R 5-19, and inspiratory reactance at 5 Hz tended to improve, despite not reaching statistical significance. The decrease in dyspnea at 60 and 120 minutes after AS significantly correlated with baseline R 5-19 (r 2 0.49, P <.01 and r 2 0.29, P <.05, respectively), but not with VC % predicted, SNIP % predicted, time since symptom onset, and clinical severity score for patients affected by amyotrophic lateral sclerosis. These findings suggest that dyspnea in neuromuscular diseases is related to heterogeneous ventilation rather than inspiratory muscle force and/or lung volumes decrease. Restoring ventilation distribution across the lungs with AS appears to improve dyspnea. [ABSTRACT FROM AUTHOR]

Background and Aims: Beyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort.Methods and Results: In this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19-34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148-1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44-53.95; p = 0.016).Conclusions: HCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors. [ABSTRACT FROM AUTHOR]

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The purpose of our work was to evaluate the feasibility of prostate multiparametric MR imaging at 1.5-T without endorectal coil using an 8 channel pelvic phased array coil. A total of 154 patients who underwent mp-MRI were retrospectively included. Patients received a standardized mp-MRI, compliant with 2012 European Society of Uro-Radiology guidelines, with 1·5 T magnetic field strength and an 8 channel pelvic phased-array coil. Two blinded readers graded the image quality of mp-MRI on a three-point scale and they scored the prostate lesions according to PI-RADS v2. All PI-RADS of 4 or 5 underwent biopsy. A third radiologist and a pathologist verified the correspondence between the MRI images and the results of the biopsy. 64 (41.6%) patients showed a Pi-rads of 4 or 5. At biopsy, 79.7% showed a Gleason score ≥7, 12.5% showed a Gleason score of 6 and 7.8% showed a negative biopsy. In the group of Pi-rads ≤ 3, 12 patients underwent a biopsy with the following results: negative biopsy in 33.3%, atypical Small Acinar Proliferation in 16.7%, prostatic intraepithelial neoplasia in 25% and indolent PCa 25%. Mp-MRI in the identification of clinically significant cancer provided a low percentage of false positive (7.8%) while in 79.7% of cases it was capable to detect clinically significant prostate cancer. In 92.2% of patients mp-MRI identified a prostate cancer with a Gleason score ≥6. The inter-reader agreement was excellent in defining both the quality of the examination and the PI-RADS category (k = 0.83 and k = 0.70, respectively). mp-MRI at 1.5-T without endorectal coil using an 8 channel phased array is an appropriate tool for early detection of clinically significant prostate cancer. 8 channel pelvic phased array is still an appropriate tool for early detection of clinically significant prostate cancer and for obtaining a reduction in overdiagnosis of indolent PCa. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis (LC) undergoing cardiac surgery (CS) face perioperative high mortality and morbidity, but extensive studies on this topic are lacking. All adult patients with LC undergoing a CS procedure between 2000 and 2017 at 10 Italian Institutions were included in this retrospective cohort study. LC was classified according to preoperative Child-Turcotte-Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score. Early-term and medium-term outcomes analysis was performed in the overall population and according to CTP classes. The study population included 144 patients (mean age 66 ± 9 years, 69% male). Ninety-eight, 20, and 26 patients were in CTP class A, in early CTP class B (MELD score <12), or advanced CTP class B (MELD score >12), respectively. The main LC etiologies were viral (43%) and alcoholic (36%). Liver-related clinical presentation (ascites, esophageal varices, and encephalopathy) and laboratory values (estimated glomerular filtration rate, serum albumin, and bilirubin, platelet count) significantly worsened across the CTP classes (P =.001). Coronary artery bypass grafting or valve surgery (87% bioprosthesis) were performed in 36% and 50%, respectively. Postoperative complications (especially acute kidney injury, liver complication, and length of stay) significantly worsened in advanced CTP class B (P =.001). Notably, observed mortality was 3-fold or 4-fold higher than the EuroSCORE (European System for Cardiac Operative Risk Evaluation) II–predicted mortality, in the overall population, and in the subgroups. At Kaplan-Meier analysis, 1-year and 5-year cumulative survival in the overall population was 82% ± 3% and 77% ± 4%, respectively. The 5-year survival in CTP class A, early CTP class B, and advanced CTP class B was 72% ± 5%, 68% ± 11%, and 61% ± 10%, respectively (P =.238). CS outcomes in patients with LC are significantly affected in relation to the extent of preoperative liver dysfunction, but in early CTP classes, medium-term survival is acceptable. Further analysis are needed to better estimate the preoperative risk stratification of these patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Aberrant right subclavian artery is a relatively rare congenital anomaly of the aortic arch. A 74-year-old woman was referred to our cardiac surgery department for chest pain. Computed tomography angiography scan showed an acute aortic dissection and revealed an aberrant right subclavian artery routed behind the trachea. We performed supracoronary ascending aorta and total arch replacement with the frozen elephant trunk technique. The aberrant right subclavian artery was then anastomosed termino-terminal to one branch of the Thoraflex (Vascutek, Glasgow, Scotland) arch graft. Postoperative computed tomography scan indicated a successful reconstruction of the aortic arch, proving the open stent-grafting technique as a useful and effective approach for aortic disease with aberrant right subclavian artery. [ABSTRACT FROM AUTHOR]

This study sought to assess the diagnostic accuracy of cardiac computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) with positron emission tomography/computed tomography (PET/CT) in defining the nature of cardiac masses. The diagnostic accuracy of cardiac CT and 18F-FDG PET/CT in identifying the nature of cardiac masses has been analyzed to date only in small samples. Of 223 patients with echocardiographically diagnosed cardiac masses, a cohort of 60 cases who underwent cardiac CT and 18F-FDG PET/CT was selected. All masses had histological confirmation, except for a minority of thrombotic formations. For each mass, 8 morphological CT signs, standardized uptake value (SUV max , SUV mean), metabolic tumor volume, and total lesion glycolysis in 18F-FDG PET were used as diagnostic markers. Irregular tumor margins, pericardial effusion, invasion, solid nature, mass diameter, CT contrast uptake, and pre-contrast characteristics were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of 3 or 4 CT signs did not accurately discriminate the masses' nature. The mean SUV max , SUV mean , metabolic tumor volume, and total lesion glycolysis values were significantly higher in malignant than in benign masses. The diagnostic accuracy of SUV, metabolic tumor volume, and total lesion glycolysis 18F-FDG PET/CT parameters was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, the presence of at least 1 abnormal 18F-FDG PET/CT parameter significantly increased the identification of malignancies. Cardiac CT is a powerful tool to diagnose cardiac masses as the number of abnormal signs was found to correlate with the lesions' nature. Similarly, 18F-FDG PET/CT accurately identified malignant masses and contributed with additional valuable information in diagnostic uncertainties after cardiac CT. These imaging tools should be performed in specific clinical settings such as involvement of great vessels or for disease-staging purposes. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden death due to ventricular arrhythmias (VAs). The implantable cardioverter-defibrillator (ICD) is a well-established therapy for treatment of VA. Monomorphic ventricular tachycardias (MVTs) are frequent in HCM patients and suitable for antitachycardia pacing (ATP) termination.Objective: The purpose of this study was to describe ventricular tachycardia (VT) characteristics in a population of HCM patients with ICD and to study the effectiveness and safety of ATP for MVT.Methods: Data were obtained from the multicenter prospective observational UMBRELLA trial, which included all patients with HCM and ICD followed by the CareLink Monitoring System. All episodes of VA were collected and analyzed. ATP effectiveness and safety were described, and factors related to ATP effectiveness were studied with generalized estimating equation (GEE) models.Results: Among 251 patients followed for 47 months, 67 (26.7%) were implanted as secondary prevention. Fifty-six patients presented 326 episodes of VA (286 [87%] MVT). Mean cycle length was 312 ± 64 ms. Among 264 MVTs that received ICD therapy, 202 (76.5%) were ATP terminated. The first ATP burst was effective in 169 episodes (68.4%), and overall effectiveness of the first or second ATP burst was 73.8%. Multivariate GEE-adjusted analysis showed 2 variables related to ATP effectiveness: programming fast VT zone On vs Off (odds ratio [OR] 2.4; 95% confidence interval [CI] 1.5-5.2; P = .03) and programming ≥2 ATP bursts vs 1 burst only (OR 1.6; 95% CI 1.2-3.4; P = .04; and OR 2.9; 95% CI 1.8-6.3; P = .02; respectively).Conclusion: MVT is the predominant VA in HCM patients with ICD. ATP is highly effective in terminating the majority of MVTs, and its proved effectiveness should guide device selection and programming in order to avoid unnecessary high-energy shocks. [ABSTRACT FROM AUTHOR]

We report on a large series of patients treated at the S. Orsola Hospital, University of Bologna (Bologna, Italy) and Hannover Medical School (Hannover, Germany), with the aim to evaluate the early and midterm results. Between January 2007 and March 2017, 437 patients underwent total aortic arch replacement with the frozen elephant trunk technique. The frozen elephant trunk prostheses used were the custom-made Chavan-Haverich (Hanover, Germany) (n = 27, 6%), Jotec E-vita open (Jotec Inc, Hechingen, Germany) (n = 192, 44%), and Vascutek Thoraflex-Hybrid (Vascutek, Inchinnan, Scotland) (n = 218, 50%). The main indications were thoracic aortic aneurysm (n = 135, 31%), chronic aortic dissection (n = 182, 41.6%), and acute aortic dissection (n = 120, 27.5%). Overall in-hospital mortality was 14.9%, and permanent neurologic deficit and spinal cord injury were 10.8% and 5.5%, respectively. Patients with chronic aortic dissection presented a better in-hospital mortality rate than the thoracic aortic aneurysm and acute aortic dissection groups. Independent risk factors for mortality in the overall population were prolonged cardiopulmonary bypass time, age, urgent/emergency surgery, and Marfan syndrome. The median (p25, p75) follow-up time was 2.6 (1.4-4.4) years, and the mortality rate was 7.01 (95% confidence interval, 5.7-8.7) per 100 patient-years. A total of 86 patients (23.1%) required an additional procedure during the follow-up; 61 (16.3%) required endovascular extensions, and 25 (6.7%) required aortic surgery. The frozen elephant trunk technique is a treatment option for all complex pathologies of the thoracic aorta. Patients with thoracic aortic aneurysms presented a higher mortality rate, and in patients with acute aortic dissection, the malperfusion syndrome still remains a catastrophic complication. The midterm follow-up showed satisfactory results in terms of survival and freedom from reintervention. [ABSTRACT FROM AUTHOR]

[Display omitted] • The aqueous extract from Anabasis articulata (AAE) induces senescence in MDA-MB-231 tumor cells. • AAE shows preventive and therapeutic antineoplastic potentialities against human breast cancer. • Derivatives from Anabasis articulata can be used as nutraceutical and functional foods. • Ethnobotanical application of AAE for fighting breast cancer finds a scientific basis in this contribution. Ancient ethnobotanical practices handed down through traditional knowledge are still commonly employed to treat various pathologies, although the scientific reasons underlying their biological effects have not been clarified yet. In this contribution, the potential antitumoral activity of the aqueous extract from A. articulata (AAE) was investigated to validate the hypothesis of the Algerian folk medicine which would suggest this plant derivative as a functional food for treating breast cancer. A. articulata phytocomplex, isolated by maceration following exactly the African recipe, has been already characterized by our research group in previous works. Thus, the antiproliferative function of AAE against MDA-MB-231, a highly aggressive human breast adenocarcinoma cell line, was evaluated. Slowing down of cell growth, absence of cytotoxicity and DNA fragmentation, and cell cycle arrest at the G2/M phase were observed after treatment with AAE at different doses (0.3–6 mg of dried plant material equivalent per mL of culture medium) for 24 and 48 h. Wound and transwell assays proved that AAE possessed both antimigration and antiinvasive capacities, evidence also supported by molecular analyses focused on Metalloproteases (MMP-2 and MMP-9), Vimentin and ανβ3-Integrin. These results, together with the demonstration of the activation of p53/p21WAF1/Cip1/p27Kip1 pathway and the increase of oxygen reactive species levels, suggested that AAE triggered a senescence process. The final confirmation was obtained by a specific kit staining senescent cells. All our data would explain the efficacy of the Algerian medicinal remedy based on the intake of the investigated functional plant food and would highlight the basics for developing novel natural pharmacological products based on AAE and showing preventive and therapeutic antineoplastic potentialities against highly aggressive breast cancers. [ABSTRACT FROM AUTHOR]