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Liver transplantation (LT) is the only effective treatment for acute-on-chronic liver failure (ACLF), but it is limited by organ availability. This study aims to identify predictive factors of mortality for LT candidates based on parameters measured at the admission into the ICU.Sixty-four patients diagnosed with ACLF, admitted consecutively into ICU between 2015 and 2019, were retrospectively enrolled in the study. Data were assessed using univariate and multivariate regression analyses to identify risk factors for inhospital mortality and 1-year mortality.A total of 67% of patients were diagnosed with ACLF grade 3, and 25 and 8% with grades 2 and 1. Thirty percent received LT with a 1-year mortality rate of 16%, whereas for nontransplanted patients it reached 90%. Clinical features were compared according to transplant eligibility. In the univariate analysis model, lung failure (HR, 3.01; 95% CI, 1.48-6.09; P = 0.002), high lactate levels (HR, 1.03; 95% CI, 1.02-1.04; P0.001) and CLIF-ACLF score (HR, 1.04; 95% CI, 1.01-1.09; P = 0.026) were independently correlated to increased inhospital mortality. LT reduced mortality risk (HR, 0.16; 95% CI, 0.04-0.72; P = 0.016).Lung failure, CLIF-ACLF score and blood lactate levels at admission were the only statistically significant independent predictors of inhospital mortality, more accurate in determining transplant success than ACLF grade.

Objectives The introduction of selective antegrade cerebral perfusion technique as method of cerebral protection improved the outcome of open arch surgery. The aim of this study was to report early outcomes using this technique. Methods Between 1997 and 2017, data were collected retrospectively for all patients who underwent surgical replacement of the aortic arch using selective antegrade cerebral perfusion ( n = 938). To confirm the effectiveness of this cerebral protection method, early outcome and results were evaluated. Results The incidence of postoperative permanent neurological dysfunction was 6.4%. Overall hospital mortality was 11.9% ( n = 112). On multivariable analysis, age >75 years, female gender, euroscore at increment of 1 point, chronic renal failure, extension of thoracic aorta replacement and CPB time emerged as independent risk factors for hospital mortality. The mid-term survival at 1, 5, 10 and 15 years was 92%, 78%, 60% and 49%, respectively. The competing risk analysis for permanent neurological dysfunction and aortic reoperations was performed excluding the patients who died during the hospital stay. The cumulative incidence of permanent neurological dysfunction and aortic reoperations was 2% at 3 years, 3% at 5 years, 6% at 10 years, 12% at 3 years, 15% at 5 years and 19% at 10 years, respectively. Conclusions From the early 90s to the present day, the selective antegrade cerebral perfusion has confirmed to be a useful and “safe” method of brain protection in aortic arch surgery in terms of postoperative neurological complications.

Background Incidence and long-term clinical consequences of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) are still unclear. Methods We enrolled 710 consecutive patients who underwent TAVR. PPM was defined as absent if the index orifice area (iEOA) was >0.85 cm2/m2, moderate if the iEOA was between 0.65 and 0.85 cm2/m2 or severe if the iEOA was Results Among the 566 patients fulfilling the study criteria, the distribution of PPM was as follows: 50.5% none (n = 286), 43% moderate PPM (n = 243) and 6.5% severe PPM (n = 37). At 5-year follow-up, patients with severe PPM had a significantly higher incidence of the combined endpoint of cardiovascular death, acute myocardial infarction and stroke (p = .025) compared with the other patients. After adjusting the results for possible confounders, severe PPM remained an independent predictor of long-term adverse outcome (HR: 2.46; 95% Confidence Interval: 1.10–5.53). The independent predictors of severe PPM were valve-in-valve procedure and body mass index. Balloon-expandable valves were not associated with higher rates of severe PPM in comparison with self-expandable valves (8% vs. 5%, respectively, p = .245). Conclusions In our study severe PPM emerged as a risk factor for long-term major adverse cardiac and cerebrovascular events.

This study sought to investigate the impact of elective, uncomplicated target lesion revascularization (TLR) on long-term cardiac mortality after percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) disease. Consecutive patients undergoing PCI for ULMCA disease between January 2003 and December 2015 in 1 interventional center in Northern Italy were included. Patients presenting with cardiogenic shock, ST-segment elevation myocardial infarction (MI), as well as those undergoing urgent or complicated TLR were excluded. The primary endpoint of the study was cardiac mortality. Among the 418 patients fulfilling the study criteria, 79 (18.46%) underwent elective, uncomplicated TLR. After a median follow-up of 5.5 years, there were 23 cardiac deaths among patients undergoing elective, uncomplicated TLR versus 50 in patients not undergoing TLR. After adjusting for possible confounders, TLR was an independent predictor of cardiac mortality (Hazard ratio [HZ] = 1.92, 95% confidence interval [CI]: 1.05 to 3.49; p = 0.03). Patients undergoing TLR had also significantly higher rates of the composite of cardiac death, MI and stroke compared with the no TLR group (adjusted HR = 1.76, 95% CI 1.14 to 2.72). In conclusion, elective, uncomplicated TLR after PCI of ULMCA disease is associated with increased risk of long-term cardiac mortality. Reducing the risk of TLR after PCI of ULMCA disease may potentially improve the survival of these patients.

Little evidence is available regarding the risk of hepatic decompensation (HD) after direct-acting antivirals (DAAs) in patients with advanced chronic liver disease. Our aim was to assess the risk of decompensation and the prognostic role of noninvasive tests, such as liver (LSM) and spleen (SSM) stiffness measurements, in the prediction of decompensation after sustained virologic response (SVR) by DAAs.A cohort study involving 146 cirrhotic patients treated with DAAs in our tertiary center with LSM and SSM available both before and six months after treatment (SVR24). A historical cohort of 92 consecutive cirrhotic patients with active HCV was used as a control group. A propensity score inverse probability weighting method was used to account for differences between the groups. Time-dependent models for the prediction of decompensation were applied to account for changes in noninvasive tests after therapy.The decompensation incidence in the DAA cohort was 7.07 (4.56-10.96) per 100 person-years (PYs), which was significantly lower than in the active HCV cohort. The DAA therapy was an independent protective factor for HD development (SHR: 0.071, 95 %-CI: 0.015-0.332). SSM ≥ 54 kPa was independently associated with decompensation despite SVR achievement (SHR: 4.169, 95 %-CI: 1.050-16.559), alongside with a history of decompensation (SHR: 7.956, 95 %-CI: 2.556-24.762). SSM reduction 10 % also predicted the risk of decompensation after SVR24.The risk of decompensation was markedly reduced after DAA therapy, but it was not eliminated. Paired SSM values stratified the risk of decompensation after SVR better than other noninvasive tests.ZIEL: Über das Risiko einer hepatischen Dekompensation (HD) nach direkt antiviral wirksamen Substanzen (DAA) bei Patienten mit fortgeschrittener chronischer Lebererkrankung gibt es nur wenig Evidenz. Unser Ziel war es, das Risiko einer Dekompensation und den prognostischen Wert nichtinvasiver Tests wie Messungen der Lebersteifigkeit (LSM) und Milzsteifigkeit (SSM) zur Vorhersage einer Dekompensation nach anhaltendem virologischem Ansprechen (SVR) unter DAA zu bewerten.Kohortenstudie mit 146 Zirrhose-Patienten, die in unserem Tertiärzentrum mit DAAs behandelt wurden, wobei LSM und SSM sowohl vor als auch 6 Monate nach der Behandlung verfügbar waren (SVR24). Eine historische Kohorte von 92 konsekutiven zirrhotischen Patienten mit aktiver HCV wurde als Kontrollgruppe verwendet. Um die Unterschiede zwischen den Gruppen zu berücksichtigen, wurde die Propensity-Score-Methode („inverse probability weighting“) verwendet. Zeitabhängige Modelle zur Prädiktion der Dekompensation wurden angewandt, um Veränderungen in den nichtinvasiven Tests nach Therapie zu berücksichtigen.Die Dekompensations-Inzidenz in der DAA-Kohorte betrug 7,07 (4,56–10,96) pro 100 Personenjahre (PYs), was signifikant niedriger war als in der aktiven HCV-Kohorte. Die DAA-Therapie war ein unabhängiger protektiver Faktor für die Entwicklung einer HD (SHR: 0,071; 95 %-KI 0,015–0,332). SSM ≥ 54kPa war trotz erfolgreichem SVR unabhängig mit Dekompensation assoziiert (SHR: 4,169; 95 %-KI 1,050–16,559), zusammen mit früher aufgetretener Dekompensation (SHR: 7,956; 95 %-KI 2,556–24,762). Eine SSM-Reduktion 10 % sagte auch das Risiko einer Dekompensation nach SVR24 voraus.Das Risiko einer Dekompensation war nach DAA-Therapie deutlich reduziert, aber nicht eliminiert. Gepaarte SSM-Werte stratifizierten das Risiko einer Dekompensation nach SVR besser als andere nichtinvasive Tests.

Background To assess whether coronary bypass (CABG) or stenting reduce the risk of mortality and myocardial infarction (MI) compared with optimal medical therapy (OMT) in stable coronary artery disease (CAD). Methods We performed a systematic review and network meta-analysis of contemporary randomized controlled trials comparing OMT, CABG and different stent types in stable CAD. All-comer trials were included if the rate of patients with acute myocardial infarction (AMI) was≤20%. Endpoints were all-cause mortality and MI. Results Ninety-seven trials including 75,754 patients were analyzed at a weighted mean follow up of 42.5 months. Compared to OMT, CABG was associated with a lower risk of death (OR = 0.84; 95%CI:0.71–0.97). After exclusion of trials in left main and/or multivessel disease(LM/MVD) this benefit was not statistically significant (OR = 0.89; 95%CI:0.74–1.06). CABG was associated with a lower risk of MI (OR = 0.67;95%CI: 0.49–0.91) showing, however, a certain degree of inconsistency (p=0.10). None of the stent types included was associated with a lower risk of death. However, durable-polymer-CoCr-everolimus-eluting stent, by mixed evidence, after exclusion of either LM/MVD (OR = 0.73;95%CI: 0.54–0.98) or all-comer/post-MI trials (OR = 0.62;95%CI:0.39–0.98) was associated with a lower risk of MI than OMT. Similar findings, by indirect evidence, were confirmed for bio-absorbable-polymer-CoCr-sirolimus eluting stent (LMV/MVD trials excluded OR = 0.46; 95%CI = 0.29–0.74, all-comer/post-MI trials excluded: OR = 0.41;95%CI:0.22–0.79). Conclusions In stable CAD, CABG reduces the risk of mortality and MI compared to OMT, especially in patients with higher extent of CAD. Our study suggests that some of second and latest-generation drug-eluting stents may reduce the risk of MI. Future research should confirm these latter findings.

Objectives The aim of this study was to investigate the safety and efficacy of coronary protection by preventive coronary wiring and stenting across the coronary ostia in patients at high risk for coronary obstruction after transcatheter aortic valve replacement (TAVR). Background Coronary obstruction following TAVR is a life-threatening complication with high procedural and short-term mortality. Methods Data were collected retrospectively from a multicenter international registry between April 2011 and February 2019. Results Among 236 patients undergoing coronary protection with preventive coronary wiring, 143 had eventually stents implanted across the coronary ostia after valve deployment. At 3-year follow-up, rates of cardiac death were 7.8% in patients receiving stents and 15.7% in those not receiving stents (adjusted hazard ratio: 0.42; 95% confidence interval: 0.14 to 1.28; p = 0.13). There were 2 definite stent thromboses (0.9%) in patients receiving stents, both occurring after TAVR in “valve-in-valve” procedures. In patients not receiving stents, there were 4 delayed coronary occlusions (DCOs) (4.3%), occurring from 5 min to 6 h after wire removal. Three cases occurred in valve-in-valve procedures and 1 in a native aortic valve procedure. Distance between the virtual transcatheter valve and the protected coronary ostia Conclusions In patients undergoing TAVR at high risk for coronary obstruction, preventive stent implantation across the coronary ostia is associated with good mid-term survival rates and low rates of stent thrombosis. Patients undergoing coronary protection with wire only have a considerable risk for DCO.

Background: The number of harvested lymph nodes (LNs) in colorectal cancer surgery relates to oncologic radicality and accuracy of staging. In addition, it affects the choice of adjuvant therapy, as well as prognosis. The American Joint Committee on Cancer defines at least 12 LNs harvested as adequate in colorectal cancer resections. Despite the importance of the topic, even in high-volume colorectal centres the rate of adequacy never reaches 100%. The aim of this study was to identify factors that affect the number of harvested LNs in oncologic colorectal surgery. Materials and methods: We prospectively collected all consecutive patients who underwent colorectal cancer resection from January 1st 2013 to December 31st 2017 at Emergency Surgery Unit St Orsola University Hospital of Bologna. Results: Six hundred and forty-three consecutive patients (382 elective, 261 emergency) met the study inclusion criteria. Emergency surgery and laparoscopic approach did not have a significant influence on the number of harvested LNs. The adequacy of lymphadenectomy was negatively affected by age >80 (OR 3.47, p < 0.001), ASA score ≥3 (OR 3.48, p < 0.001), Hartmann's or rectal resection (OR 3.6, p < 0.001) and R1–R2 resection margins (OR 3.9, p = 0.006), while it was positively affected by T-status ≥3 (OR 0.33 p < 0.001). Conclusion: Both the surgical technique and procedure regimen did not affect the number of lymphnodes retrieved. Age >80 and ASA score ≥3 and Hartmann's procedure or rectal resection showed to be risk factors related to inadequate lymphadenectomy in colorectal cancer surgery.

Aims: We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. Material and methods: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced-induced thrombus deposition was determined using 125I-fibrinogen. Results: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface-induced thrombus formation, with a significant difference compared to Vision (125I-fibrinogen median value deposition [IQ range]: 50 ng [25-98] versus 560 ng [320-1520], respectively, p < 0.05), but not to other DES. In the second set of experiments Fluoropolymer-coated BMS not eluting drug was associated with a significant 3-fold reduction in 125I-fibrinogen deposition (245 ng [80-300]) compared to Vision (625 ng [320-760], p < 0.05), but a 7-fold increase compared to Xience (35 ng [20-60], p < 0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. Conclusions: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface-induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.

Background The prognostic role of spontaneous portosystemic shunts (SPSS) has been poorly investigated. Aims To evaluate the impact of the presence of SPSS, as well as their characteristics, on the risk of decompensation. Methods This is a retrospective cohort study of 235 advanced chronic liver disease (ACLD) patients with available imaging examination, transient elastography, and upper endoscopy. ACLD was defined as liver stiffness measurement (LSM) >10 kPa. Competitive risk analyses were performed to identify the factors associated with the main outcome. Results SPSS were reported in 141 (60%) of the patients. Non-viral etiology was independently associated with SPSS presence [Odds-Ratio (OR): 2.743;95%-Interval-of-Confidence (IC):1.129–6.664]. During a follow-up of 37 (20–63) months, SPSS were found predictors of any decompensation type [Subhazard Ratio (SHR):2.264; 95%-IC:1.259–4.071], independently from a history of decompensation or high-risk-varices presence. The risk of complications was higher in patients with large (SHR: 3.775; 95%-IC: 2.016–7.070) and multiple (SHR:3.832; 95%-IC: 2.004–7.330) shunts, and in those with gastrorenal shunts (SHR:2.636; 95%-IC:1.521–4.569). Conclusions The presence, size, and number of SPSS predict not only the risk of hepatic encephalopathy but that of any type of decompensation across all stages of cirrhosis. Future studies should explore the possibility of treating shunts to prevent decompensation.

Background and Aims: Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Methods: Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients’ sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Results: Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B – TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 – 18.297, p=0.024). Conclusion: IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

Objective To rapidly and safely identify the risk of developing acute coronary syndrome in patients with chest pain who present to the emergency department, the clinical use of the History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) scoring has recently been proposed. This study aimed to assess the inter-rater reliability of the HEART score calculated by a large number of Italian emergency physicians. Methods The study was conducted in three academic emergency departments using clinical scenarios obtained from medical records of patients with chest pain. Twenty physicians, who took the HEART score course, independently assigned a score to different clinical scenarios, which were randomly administered to the participants, and data were collected and recorded in a spreadsheet by an independent investigator who was blinded to the study's aim. Results After applying the exclusion criteria, 53 scenarios were finally included in the analysis. The general inter-rater reliability was good (kappa statistics [κ], 0.63; 95% confidence interval, 0.57 to 0.70), and a good inter-rater agreement for the high- and low-risk classes (HEART score, 7 to 10 and 0 to 3, respectively; κ, 0.60 to 0.73) was observed, whereas a moderate agreement was found for the intermediate-risk class (HEART score, 4 to 6; κ, 0.51). Among the different items of the HEART score, history and electrocardiogram had the worse agreement (κ, 0.37 and 0.42, respectively). Conclusion The HEART score had good inter-rater reliability, particularly among the high- and low-risk classes. The modest agreement for history suggests that major improvements are needed for objectively assessing this component.

Purpose: Intrapartum antibiotic prophylaxis (IAP) prevents group B streptococcus (GBS) early-onset disease (EOD). No European study evaluates the relative impact of risk factors (RFs) for EOD after...

Background & Aims Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease. Methods We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC. Results We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins Conclusions SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis. Lay summary The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis.

Background Senior adults fear postoperative loss of independence the most, and this might represent an additional burden for families and society. The number of geriatric patients admitted to the emergency room requiring an urgent surgical treatment is rising, and the presence of frailty is the main risk factor for postoperative morbidity and functional decline. Frailty assessment in the busy emergency setting is challenging. The aim of this study is to verify the effectiveness of a very simple five-item frailty screening tool, the Flemish version of the Triage Risk Screening Tool (fTRST), in predicting functional loss after emergency surgery among senior adults who were found to be independent before surgery. Methods All consecutive individuals aged 70 years and older who were independent (activity of daily living (ADL) score ≥5) and were admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 were prospectively included in the study. On admission, individuals were screened using the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index (CACI) and the ASA score. Thirty- and 90-day complications and postoperative decline in the ADL score where recorded. Regression analysis was performed to identify preoperative predictors of functional loss. Results Seventy-eight patients entered the study. Thirty-day mortality rate was 12.8% (10/78), and the 90-day overall mortality was 15.4% (12/78). One in every four patients (17/68) experienced a significant functional loss at 30-day follow-up. At 90-day follow-up, only 3/17 patients recovered, 2 patients died, and 12 remained permanently dependent. On the regression analysis, a statistically significant correlation with functional loss was found for fTRST, CACI, and age≥85 years old both at 30 and 90 days after surgery. fTRST≥2 showed the highest effectiveness in predicting functional loss at 90 days with AUC 72 and OR 6.93 (95% CI 1.71–28.05). The institutionalization rate with the need to discharge patients to a healthcare facility was 7.6% (5/66); all of them had a fTRST≥2. Conclusion fTRST is an easy and effective tool to predict the risk of a postoperative functional decline and nursing home admission in the emergency setting.

At the time of late-onset disease, mothers often have positive breast milk culture or group B Streptococcus bacteriuria, suggesting heavy maternal colonization., We retrospectively investigated mother-to-infant transmission of group B Streptococcus (GBS) in 98 cases of late-onset disease reported during 2007–2018 by a network in Italy. Mothers with full assessment of vaginal/rectal carriage tested at prenatal screening and at time of late onset (ATLO) were included. Thirty-three mothers (33.7%) were never GBS colonized; 65 (66.3%) were vaginal/rectal colonized, of which 36 (36.7%) were persistently colonized. Mothers with vaginal/rectal colonization ATLO had high rates of GBS bacteriuria (33.9%) and positive breast milk culture (27.5%). GBS strains from mother–infant pairs were serotype III and possessed the surface protein antigen Rib. All but 1 strain belonged to clonal complex 17. GBS strains from 4 mother–infant pairs were indistinguishable through pulsed-field gel electrophoresis. At least two thirds of late-onset cases are transmitted from mothers, who often have vaginal/rectal carriage, positive breast milk culture, or GBS bacteriuria, which suggests heavy maternal colonization.

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Background isolated distal deep vein thromboses (IDDVT) are frequent; however, their optimal management is still controversial. Methods we performed a retrospective study on inpatients undergoing ultrasound for suspected deep vein thrombosis (DVT) or with a particular risk profile, during 2016. The study was aimed to assess the frequency of proximal deep vein thromboses (PDVT) and IDDVT; to evaluate therapeutic management and identify variables associated with early outcomes and mortality among IDDVT patients; to compare all-causes mortality between subjects with PDVT and IDDVT. Results among 21594 patients hospitalized in the study period 251 IDDVT and 149 PDVT were diagnosed; the frequency was 1.2 % and 0.7% respectively. 19% of IDDVT patients died compared to 25,5% of PDVT subjects (OR 0.72; 95% CI 0.44-1.17; p 0.19). In IDDVT patients, age ≥ 80, cancer and intracranial bleeding increased the risk of death (OR 2; 95% CI 1.07-3.75, p 0.001; OR 8.47; 95% CI 3.28-21.88, p 0.0000003; OR 2.33; 95% CI 1.18-4.58, p 0.0003). A significant association between intracranial hemorrhage and both proximal extension by using the Fisher's exact test (p 0.031; OR 16.11; 95% CI 0.80-321.2), and composite of propagation to popliteal or to other calf veins (OR 8.28, 95% CI 2.07-33 p 0.001) was observed. Standard anticoagulation significantly reduced the composite of propagation to popliteal or to other calf veins (OR 0.07; 95% CI 0.009-0.61, p 0.007), and all-causes mortality (OR 0.37; 95% CI 0.17-0.8; p 0.02), without a significant increase of bleeding. Conclusions among inpatients, IDDVT exceeded 60% of DVT. Mortality was not significantly different between IDDVT and PDVT subjects. Intracranial bleeding significantly increased the risk of propagation and death. Although standard anticoagulation decreased both these complications, further targeted studies are needed.

BackgroundMost studies regarding late-onset sepsis (LOS) address selected populations (i.e., neonates with low birth weight or extremely preterm neonates). Studying all age groups is more suitable to assess the burden of single pathogens and their clinical relevance.MethodsThis is a retrospective regional study involving paediatric departments and NICUs in Emilia-Romagna (Italy). Regional laboratory databases were searched from 2009 to 2012. Records of infants (aged 4 to 90 days) with a positive blood or cerebrospinal fluid (CSF) culture were retrospectively reviewed and analysed according to acquisition mode (whether hospital- or community-acquired).ResultsDuring the study period, there were 146,682 live births (LBs), with 296 patients experiencing 331 episodes of LOS (incidence rate: 2.3/1000 LBs). Brain lesions upon discharge from the hospital were found in 12.3% (40/296) of cases, with death occurring in 7.1% (23/296; 0.14/1000 LBs). With respect to full-term neonates, extremely preterm or extremely low birth weight neonates had very high risk of LOS and related mortality (> 100- and > 800-fold higher respectively). Hospital-acquired LOS (n = 209) was significantly associated with very low birth weight, extremely preterm birth, pneumonia, mechanical ventilation, and death (p< 0.01). At multivariate logistic regression analysis, catecholamine support (OR = 3.2), central venous line before LOS (OR = 14.9), and meningitis (OR = 44.7) were associated with brain lesions or death in hospital-acquired LOS (area under the ROC curve 0.81, H-L p = 0.41). Commonly identified pathogens included coagulase-negative staphylococci (CoNS n = 71, 21.4%), Escherichia coli (n = 50, 15.1%), Staphylococcus aureus (n = 41, 12.4%) and Enterobacteriaceae (n = 41, 12.4%). Group B streptococcus was the predominant cause of meningitis (16 of 38 cases, 42%). Most pathogens were sensitive to first line antibiotics.ConclusionsThis study provides the first Italian data regarding late-onset sepsis (LOS) in all gestational age groups. Compared to full-term neonates, very high rates of LOS and mortality occurred in neonates with a lower birth weight and gestational age. Group B streptococcus was the leading cause of meningitis. Excluding CoNS, the predominant pathogens were Escherichia coli and Staphylococcus aureus. Neonates with hospital-acquired LOS had a worse outcome. Antibiotic associations, recommended for empirical treatment of hospital- or community-acquired LOS, were adequate.

Introduction: Coarctation of the aorta (CoA) is common and can lead to neonatal emergency. Despite its burden, antenatal detection of this condition remains inaccurate. Objective: To evaluate the diagnostic performance of fetal echocardiography and to design a scoring system for risk stratification of CoA in suspected cases. Design: A retrospective cohort study. Setting: S. Orsola Hospital, Bologna, Italy. Population: About 140 fetuses referred for suspected CoA to our tertiary center in a 9-year period. Methods: The following parameters were systematically obtained at fetal echocardiography: ventricular disproportion, great vessels asymmetry, transverse aortic arch hypoplasia, flow turbulence, and Z-scores of the ascending aorta and of the aortic isthmus. Associated anomalies were recorded, if present. When CoA was not confirmed at birth, neonates were followed up for 12 months to identify also a tardive onset of this condition. Main outcome measures: The primary outcome was the presence of COA after birth. Results: 108 fetuses were eligible for the purpose of the study. CoA was confirmed postnatally in 55 neonates (50.9%). Arch hypoplasia yielded the highest correlation with CoA. The affected neonates presented also significantly lower Z scores of the ascending aorta and of the aortic isthmus. Earlier gestational age at referral was positively correlated with neonatal CoA. An odds ratio-based multiparametric model was designed to build a scoring system (AUC 0.89). Conclusion: In our cohort, no single ultrasound parameter was sufficiently accurate to predict postnatal CoA. The scoring system permitted a better identification of the affected fetuses.

Objective: To assess the histopathological findings of a large series of ascending thoracic aortic aneurysm (TAA) surgical specimens applying the updated classification on noninflammatory degenerative and inflammatory aortic diseases proposed by the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology clinicopathological correlations. Methods: A total of 255 patients surgically treated for ascending TAA were enrolled. Surgical ascending aorta specimens were examined. Results: The histopathological substrate of ascending TAAs was mainly degenerative (67.5%), but with a remarkable prevalence of atherosclerotic lesions (18.8%) and aortitis (13.7%). Degenerative patients more frequently had bicuspid aortic valve (37.2%; P = .002). Patients in the atherosclerotic group were older (median age, 69 years; P < .001), more often with a history of hypertension (87.5%; P = .059), hypercholesterolemia (75%; P = .019), diabetes (16.6%; P = .054), current smoking (22.9%; P = .066), and a history of coronary artery disease (18.7%; P = .063). Patients with aortitis represented the older group (median age, 75 years, P < .001), were mostly females (68.6%; P < .001), and had a larger ascending aorta diameter (median, 56 mm; P < .001). Both patients with atherosclerosis and aortitis presented a higher incidence of concomitant abdominal aortic aneurysm (20.8% and 22.8%, respectively; P < .001). Conclusions: Although degenerative histopathology is the most frequent substrate in ascending TAA, atherosclerosis and inflammation significantly contribute to the development of chronic aortic thoracic disease.

Background—It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods—The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results—Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions—Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.

Aims: To investigate in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) the prevalence and the features of optical coherence tomography (OCT)-detected macrophages accumulation in culprit plaques as compared with nonculprit plaques (NCP). Methods: The study is a post-hoc analysis of a prospective study aimed at evaluating the relationship between aortic inflammation as assessed by F-fluorodeoxyglucose-PET and features of coronary plaque vulnerability as assessed by OCT. We enrolled 32 patients with first NSTE-ACS who successfully underwent three-vessel OCT. Results: The median age was 65 (54-72) years and 27 patients (84%) were men. Culprit plaques were clinically defined. Overall, the rate of lipid plaques and lipid plaques containing macrophages were 6.4 and 4.2 per patient, respectively. Culprit plaques had a smaller minimal luminal area, a higher extension of lipid component and a thinner fibrous cap than NCPs. Macrophages accumulations were more likely found in culprit plaque (84 vs. 61%, P = 0.015) in which they had also a higher circumferential extension. On univariable analysis, macrophages accumulation extension had a higher association with culprit plaques (odds ratio = 4.42; 95% confidence interval; 2.54-9.15, P < 0.001) than the mere presence of macrophages accumulation (odds ratio = 3.36; 95% confidence interval; 1.30-8.66, P = 0.012). Culprit plaques with thrombus had a lower distance between macrophages accumulation and the luminal surface than culprit plaque with no thrombus (0.06 vs. 0.1 mm; P = 0.04). Conclusion: In patients with NSTE-ACS, macrophages accumulations are more likely present in culprit plaque in which they disclose also a greater extension compared with those observed in NCP. The distance between macrophages accumulation and the luminal surface is lower in thrombotic culprit plaque than that in nonthrombotic culprit plaque.

Objectives To determine whether the Flemish version of the Triage Risk Screening Tool (fTRST) can be used to accurately assess frailty in an emergency setting. Design Prospective observational study. Setting of a tertiary referral hospital. Patients All individuals aged 70 and older consecutively admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 who met inclusion criteria (N=110). Measurements Individuals were screened with the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index and American Society of Anesthesiology score. Thirty- and 90-day postoperative complications where recorded. Regression analyses were performed to identify possible preoperative predictors of adverse outcomes. Results Thirty-day major complications (Clavien-Dindo Classification 3-5) occurred in 28.2% of participants (n=31). fTRST had the highest correlation with major complications (odds ratio (OR) = 7.42). All participants who died within 30 days of surgery has a fTRST score of 2 or greater (area under the receiver operating curve (AUC)=71.3). When risk factors for overall 90-day mortality were analyzed, a fTRST score of 2 or greater had sensitivity of 96% (95% confidence interval CI=79.6-99.9%), specificity of 43.5% (95% CI=32.8-54.7%) (AUC=69.8%; OR=18.50, 95% CI=2.39-143.11, p = .005). The average length of hospital stay was more than twice as long in the group with a fTRST score of 2 or greater (15.2 days) than in those with a score less than 2 (6.6 days) (p = .005). Conclusion The fTRST is an effective tool to predict mortality, morbidity, and length of stay after emergency surgery and can therefore be used to anticipate postoperative course, determine care goals, and plan for involvement of a dedicated geriatric care team. J Am Geriatr Soc 67:309-316, 2019.

Background: The role of thrombus aspiration plus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction remains controversial. Methods: We performed a meta-analysis of 25 randomised controlled trials in which 21,740 ST-segment elevation myocardial infarction patients were randomly assigned to thrombus aspiration plus primary percutaneous coronary intervention or primary percutaneous coronary intervention. Study endpoints were: death, myocardial infarction, stent thrombosis and stroke. Results: On pooled analysis, the risk of death (4.3% vs. 4.8%, odds ratio (OR) 0.90, 95% confidence interval (CI) 0.79–1.03; P=0.123), myocardial infarction (2.4% vs. 2.5%, OR 0.95, 95% CI 0.80–1.13; P=0.57) and stent thrombosis (1.3% vs. 1.6%, OR 0.80, 95% CI 0.63–1.01; P=0.066) was similar between thrombus aspiration plus primary percutaneous coronary intervention and primary percutaneous coronary intervention. The risk of stroke was higher in the thrombus aspiration plus primary percutaneous coronary intervention than the primary percutaneous coronary intervention group (0.84% vs. 0.59%, OR 1.401, 95% CI 1.004–1.954; P=0.047). However, on sensitivity analysis after removing the TOTAL trial, thrombus aspiration plus primary percutaneous coronary intervention was not associated with an increased risk of stroke (OR 1.01, 95% CI 0.58–1.78). The weak association between thrombus aspiration and stroke was also confirmed by the fact that the lower bound of the 95% CI was slightly below unity after removing either the study by Kaltoft or the ITTI trial. There was no interaction between the main study results and follow-up, evidence of coronary thrombus, or study sample size. Conclusions: In patients with ST-segment elevation myocardial infarction, thrombus aspiration plus primary percutaneous coronary intervention does not reduce the risk of death, myocardial infarction or stent thrombosis. Thrombus aspiration plus primary percutaneous coronary intervention is associated with an increased risk of stroke; however, this latter finding appears weak.

Aims Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt). Methods and results Data of 67 Ile68Leu ATTRm patients from two Italian referral centres (Bologna and Florence) were retrospectively analysed and compared to those of 82 ATTRwt patients. Fifty-five unaffected mutation carriers were also analysed. Cumulative disease onset was 50% at age 71. A total of 56/67 (84%) patients had a predominantly cardiac phenotype at presentation with concentric increase in left ventricular wall thickness [median 17 mm], and normal or near normal left ventricular ejection fraction (79% of patients). Low QRS voltages were present only in 29% of patients but voltage/mass ratio was low (0.5). Carpal tunnel syndrome was noted in 43%. The overall phenotypic profile was similar to ATTRwt but Ile68Leu ATTRm patients typically presented younger (median 71 vs. 78 years) and were more likely to have (mild) symptomatic neurological involvement (19% vs. 2%). Male prevalence was 44% in unaffected mutation carriers and 78% in affected patients. Age-adjusted survival was comparable between groups. Conclusions Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt.

Objective To investigate differences in cardiac manifestations of patients affected by laminopathy, according to the presence or absence of neuromuscular involvement at presentation. Methods We prospectively analyzed 40 consecutive patients with a diagnosis of laminopathy followed at a single centre between 1998 and 2017. Additionally, reports of clinical evaluations and tests prior to referral at our centre were retrospectively evaluated. Results Clinical onset was cardiac in 26 cases and neuromuscular in 14. Patients with neuromuscular presentation experienced first symptoms earlier in life (11 vs 39 years; p p = 0.013] and 30 vs 44 years [p = 0.086] respectively), despite a similar overall prevalence of AF (57% vs 65%; p = 0.735) and atrio-ventricular (A-V) block (50% vs 65%; p = 0.500). Those with a neuromuscular presentation developed a cardiomyopathy less frequently (43% vs 73%; p = 0.089) and had a lower rate of sustained ventricular tachyarrhythmias (7% vs 23%; p = 0.387). In patients with neuromuscular onset rhythm disturbances occurred usually before evidence of cardiomyopathy. Despite these differences, the need for heart transplantation and median age at intervention were similar in the two groups (29% vs 23% [p = 0.717] and 43 vs 46 years [p = 0.593] respectively). Conclusions In patients with laminopathy, the type of disease onset was a marker for a different natural history. Specifically, patients with neuromuscular presentation had an earlier cardiac involvement, characterized by a linear and progressive evolution from rhythm disorders (AF and/or A-V block) to cardiomyopathy.

Post-reperfusion syndrome during orthotopic liver transplantation, which definition best predicts postoperative graft failure and recipient mortality? Purpose Post-reperfusion syndrome (PRS) is a serious complication of liver transplantation, at present two main definitions are in use, and they differ both clinically and temporally. The primary objective of this study was to evaluate these two definitions as risk factors for post-transplantation mortality and primary graft non-function. Materials and methods We conducted a retrospective observational study on 794 patients undergoing orthotopic liver transplantation at our university hospital. The presence of PRS was evaluated according to both definitions and correlated with the end points: three months mortality, primary graft non-function (PGNF) and the combined outcome of the two. Results Both definitions proved to be independent risk factors for three months mortality and the combined outcome. The definition according to Aggarwal et al. was also an independent risk factor for PGNF when adjusted for the propensity score. The Hilmi definition, despite being more comprehensive, did not improve the predictivity of the Aggarwal definition for the evaluated outcomes. Conclusions PRS proved to be an independent risk factor for post-transplantation mortality and occurrence of PGNF. The pathophysiological mechanisms of this entity are still not fully understood and preventive strategies could help in reducing patients and graft losses.

Purpose To evaluate the outcome of patients with an established indication for oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S) and stratified by the baseline risk of bleeding. Material and methods The database of the prospective, multicentre, observational WAR-STENT registry ( ClinicalTrials.gov identifier NCT00722319 ) was analyzed and patients with atrial fibrillation and CHA 2 DS 2 -VASc score ≥2, mechanical heart valve, prior cardiac embolism, intra-cardiac thrombus and recent venous thromboembolism who were treated with either triple (warfarin, aspirin and clopidogrel) or dual (warfarin and clopidogrel) or dual antiplatelet (aspirin and clopidogrel) therapy, identified. Patients were then sorted into two groups at non-low and low risk of bleeding, as defined by an ATRIA score >3 and ≤3 respectively, and compared regarding major adverse cardiac and vascular events (MACVE) and bleeding. Results At 12-month follow up, MACVE were comparable in the two groups, whereas total, major and minor bleeding, as well as combined MACVE and total bleeding, were significantly more frequent in the non-low bleeding risk group. Upon Cox univariate and multivariable analysis, non-low bleeding risk category confirmed as an independent predictor of major bleeding. The choice of antithrombotic therapy however, appeared not to be influenced by the bleeding risk category at baseline. Conclusions In patients with an established indication for OAC undergoing PCI-S, non-low bleeding risk category is the most potent independent predictor of major bleeding. Stratification of the bleeding risk at baseline should therefore be regarded as an indispensable process to be carried out before selection of the antithrombotic therapy.

Aims Pulmonary hypertension (PH) is a relevant complication of left heart disease (LHD). The 2015 ESC/ERS PH guidelines report two different haemodynamic subsets of PH due to LHD (PH-LHD) based on levels of pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG): isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). The objective of this study is to evaluate the prognostic value of Ipc-PH and Cpc-PH. Methods and results Data from 276 consecutive incident patients with PH-LHD were included. According to the guidelines, Ipc-PH is defined by DPG 3 WU. Using this definition, we identified three patient groups: Ipc-PH with both normal PVR and DPG (108 patients); Cpc-PH with both increased PVR and DPG (66 patients); and an intermediate group with either increased PVR or DPG (102 patients). Survival was estimated using the Kaplan–Meier method and compared between groups using the log-rank test. Patients with Ipc-PH had better survival compared with the group of patients with Cpc-PH (P = 0.026) and the intermediate group (P = 0.025). No survival difference was detected between patients with Cpc-PH and the intermediate group (P = 0.891). Patients with normal PVR had a better survival compared with those with elevated PVR (P = 0.012); while no difference was observed according to the level of DPG (P = 0.253). Conclusion Patients with Ipc-PH have a better prognosis compared with patients with Cpc-PH and with patients with isolated increase of PVR or DPG. Pulmonary vascular resistance has a better predictive value than DPG in patients with PH-LHD.

Our results confirm the diagnostic role of CTPA in evaluating patients with CTEPH and in addition open a new horizon in assessing hemodynamic changes in patients with CTEPH, only employing a CTPA, especially when RHC is contraindicated or not possible. Purpose: The aim of this study was to retrospectively assess the relationship between radiological and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We introduced a new CT-score to evaluate hemodynamic changes, only employing CT-pulmonary angiography (CTPA). Materials and methods: 145 patients affected by CTEPH underwent hemodynamic and CTPA evaluation. Among these 145 patients, 69 underwent pulmonary endarterectomy (PEA) and performed a CTPA evaluation even after surgery. Hemodynamic assessment considered the values of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), obtained through right heart catheterization (RHC). Radiological evaluation included CTPA signs of pulmonary hypertension. Results: A highly significant statistical correlation was observed between the new CT-score and both mPAP and PVR (p < 0.000) in the whole sample and also in the subgroup who underwent PEA. In addition, mPAP and PVR showed an important association with the severity of mosaic perfusion (p < 0.000). mPAP also correlated with main pulmonary artery diameter (p < 0.01); a significant association was found in both between PVR and tricuspid regurgitation(p < 0.000) and with PVR and presence of unilateral or bilateral pulmonary thromboembolic occlusion (p < 0.05). Conclusion: Our results confirm the diagnostic role of CTPA in evaluating patients with CTEPH and in addition open a new horizon in assessing hemodynamic changes in patients with CTEPH, only employing a CTPA, especially when RHC is contraindicated or not possible.

AIM to assess vitamin E efficacy, defined as its ability to induce hepatitis B e antigen (HBeAg) seroconversion, in children with HBeAg-positive persistent hepatitis. METHODS In July 2016, we extracted articles published in MEDLINE and the Cochrane Library using the following search terms: "chronic hepatitis B", "children", "childhood", "therapy", "treatment", "vitamin E", "tocopherols", "tocotrienols". Only randomized controlled trials (RCTs) published in English language were collected. RESULTS Three RCTs met inclusion criteria and were considered in the present meta-analysis. Overall, 23/122 children in the treatment group underwent HBeAg seroconversion vs 3/74 in the control group (OR = 3.96, 95%CI: 1.18-13.25, p = 0.025). CONCLUSION Although our meta-analysis has several limits, including the very small number of available studies and enrolled children with HBeAg positivity-related hepatitis, it suggests that vitamin E use may enhance the probability to induce HBeAg seroconversion in these patients. Further well designed and adequately sized trials are required to confirm or deny these very preliminary results.

Transcatheter aortic valve implantation (TAVI) is a valid alternative to surgical aortic valve replacement for the treatment of symptomatic aortic stenosis. The EuroScore (ES) II, logistic EuroScore (log ES), and the Society of Thoracic Surgeons (STS) score are the most applied scores for surgical risk stratification. However, their predictive value for patients undergoing TAVI is still unclear.To evaluate the performance of STS, log ES and ES II as predictors of short-term and long-term mortality in patients undergoing TAVI.Between February 2008 and October 2017, a total of 384 patients underwent transfemoral TAVI at our institution and constituted the study population. Patients were divided into three groups based on the class of risk (low, intermediate, and high) calculated by each score. In-hospital complications, 30-day outcomes, and 5-year outcomes were assessed.In-hospital mortality rate was 2.6% (n = 10). All scores over-estimated the risk of 30-day mortality, especially for the highest risk classes. At the end of follow-up (5 years), STS risk stratification was able to stratify all-cause and cardiovascular (CV) mortality (P.01 and P=.02, respectively). Patients with intermediate ES II risk showed a lower survival rate (P=.04) while CV deaths did not differ between classes of risk. All-cause mortality and CV mortality curves did not diverge according to the patients' risk profiles derived from log ES.Conventional surgical risk scores are not appropriate to predict 30-day mortality in patients undergoing transfemoral TAVI. STS assessment was the only risk score able to stratify long-term all-cause and CV mortality.

The role of circulating microvesicles (MVs) in Myelofibrosis (MF) and Essential Thrombocythemia (ET) is far to be defined. Here we found that 1) circulating megakaryocyte-MVs were reduced in MF and ET while platelet-MVs were increased; 2) the proportion of circulating megakaryocyte- and platelet-MVs was associated with disease severity in MF; 3) ruxolitinib normalized the profile of circulating megakaryocyte- and platelet-MVs in spleen responders MF patients only. Of note, a cut-off value of 19.95% of circulating megakaryocyte-MVs predicts ruxolitinib spleen response. In light of these findings, circulating megakaryocyte/platelet-MVs may have a tissue specific diagnostic and prognostic role in MF.

OBJECTIVES We compared the results of 2 groups of patients who underwent aortic arch replacement with the frozen elephant trunk technique. In the first group, the distal anastomosis was performed in arch zone 2; in the second control group, the distal anastomosis was performed in arch zone 3. METHODS Between January 2007 and April 2018, the frozen elephant trunk technique was used in 282 patients. The median age was 62 years (range 18–83 years), and 233 patients were men (82.6%). Two different frozen elephant trunk prostheses were used: the Jotec E-vita open prosthesis in 167 patients (59.2%) and the Vascutek Thoraflex hybrid prosthesis in 115 patients (40.8%). Patients were divided into 2 groups according to the distal anastomosis site: zone 2 group (69 patients) and zone 3 group (213 patients). The main indications were chronic aortic dissection (n = 164, 58.2%), degenerative aneurysm (n = 72, 25.5%) and acute aortic dissections (n = 45, 16%). RESULTS The overall in-hospital mortality rate was 17%: 20% for the zone 2 group and 16% for the zone 3 group, without significant differences, also in terms of cardiopulmonary bypass and myocardial ischaemia times. However, the visceral ischaemia time was significantly shorter for the zone 2 group, whereas the antegrade selective cerebral perfusion time was significantly longer for the same group. Recurrent laryngeal nerve injury rate was lower in the zone 2 group. The overall postoperative paraplegia rate was 3.5%, whereas the occurrence of permanent neurological dysfunction and dialysis was 9% and 19%, respectively, with no significant differences between the groups. CONCLUSIONS ‘Proximalization’ of the distal anastomosis can be used for arch reconstruction, especially in complex cases such as reoperations or acute aortic dissections. Furthermore, with the aid of branched hybrid grafts, a reduction of the visceral ischaemia time is achieved.

Background Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce. Methods We compared the efficacy of either pirfenidone (n = 78) or nintedanib (n = 28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n = 36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded. Results Over time, the decline in FVC and DLCO was significantly higher (p = 0.0053 and p = 0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups. Conclusion This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function.

Background: Although imaging techniques have demonstrated the existence of microvascular abnormalities in hypertrophic cardiomyopathy (HCM), a detailed histopathological assessment is lacking as well as a comparison between different phases of the disease. We aimed to compare microvasculopathy and myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) versus end-stage (ES) HCM. Methods: 27 myectomy specimens of HOCM patients and 30 ES-HCM explanted hearts were analyzed. Myocardial fibrosis was quantitatively determined with dedicated software and qualitatively classified as scar-like or interstitial. Intramural coronary arteries were evaluated separately according to lumen diameter: 100–500 μ versus

Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening. Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening.

AIMS: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS.METHODS AND RESULTS: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05-3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12-5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86-3.10, p = 0.131).CONCLUSIONS: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.

Objective: To evaluate the predictive value of stridor and its latency of onset and to investigate the role of stridor treatment in a cohort of patients with multiple system atrophy (MSA) referred to a tertiary center. Methods: We retrospectively identified patients diagnosed with MSA referred to our department beginning in 1991 and evaluated at least yearly during the disease course. Stridor was defined as present when confirmed by a whole night video-polysomnography and as early if presenting within 3 years of disease onset. Survival data, from disease onset to time of death, were calculated with Kaplan-Meier curves. Predictors were identified in univariate and multivariable Cox regression analyses. Results: We included 136 patients with MSA; 113 were deceased at the time of study. Stridor was diagnosed in 42 patients, and 22 presented early stridor onset. Twelve of the 31 patients treated for stridor received tracheostomy, and 19 received continuous positive airway pressure. Overall survival did not differ between patients with and without stridor, while patients with early stridor onset had a worse prognosis than those developing this symptom later. In the stridor subgroup, early stridor onset was an unfavorable survival predictor. Stridor treatment was significantly associated with survival in our population. The Kaplan-Meier curve did not reveal significant differences in survival between the 2 treatments even though there was a trend toward longer disease duration in patients receiving tracheostomy. Conclusions: Our results demonstrated that early stridor onset is an independent predictor for shorter survival and that tracheostomy could control stridor, influencing disease duration.

Background & aims The treatment of chronic hepatitis B infection (CHB) in children is still an area of great uncertainty. Vitamin E is an immunostimulating/antioxidant compound proven to be safe and effective for the treatment of adult CHB. The aim of this phase 2 controlled study was to evaluate the safety and efficacy of vitamin E for the treatment of paediatric HBeAg-positive CHB. Methods Forty-six children were randomized in a 1:1 ratio to receive vitamin E at a dose of 15 mg/kg/day (in galenic preparation) or no treatment for 12 months and were monitored for the subsequent 12 months. Clinical, biochemical, haematological and serovirological evaluations were carried out every 3 months. Results No significant side effects were associated with the vitamin E treatment. At the end of the study, anti-HBe seroconversion was obtained in 7 of 23 (30.4%) of vitamin E-treated versus 1 of 23 (4.3%) of the control patients (P = 0.05), while a virological response (≥2 log decrease in HBV-DNA from baseline) was observed in 9 of 23 (39.1%) vs. 2 of 23 (8.7%) respectively (P = 0.035). Conclusions Vitamin E administration for the treatment of paediatric CHB at the tested dosage has no significant side effects and may induce anti-HBe seroconversion. Vitamin E could represent a tool for the treatment of paediatric CHB.

CT is the recommended technique for the detection of pulmonary metastases in patients affected by osteosarcoma, though claimed to show several limits compared to manual palpation. We retrospectively analyzed CT features of suspected lesions submitted to surgery to address its current accuracy and to investigate criteria for predicting histology.CT scans of 70 patients submitted to thoracotomy between 2007-2013 were reviewed. Overall, 123 thoracotomies were performed and 283 lesions seen on CT were resected. Shape, size, presence and type of calcification, evolution of each lesion were analyzed. Number and histology of nodules detected at thoracotomy were recorded and compared to CT data.234/283--82.7% Lesions were metastases; 143--61.1% were calcified; most metastases were nodular (201/234--85.9%), but in 33/234--14.1% other findings were detected (striae, consolidations, pleural plaques/masses, cavitations, ground glass opacities, irregular shapes, halo sign). Malignant lesions were more frequently calcified, larger, with progression over time--p0.0001. Manual palpation identified 314 lesions, 248 metastatic--79.0%: CT missed 31/314--9.9% lesions, whereof 14/31--45.2% were metastases.Though most lesions are nodular and calcified, up to 40% are not calcified and atypical findings are not uncommon (14.1%). The identification of the atypical radiological presentation of metastases could be the key for improving CT accuracy.

It is unclear whether the site of origin of papillary thyroid microcarcinoma (mPTC) with respect to the thyroid surface has an influence on clinicopathologic parameters. The objectives of the study were to: (i) Accurately measure the mPTC distance from the thyroid surface, (ii) analyze whether this distance correlates with relevant clinicopathologic parameters, and (iii) investigate the impact of the site of origin of the mPTC on risk stratification. Clinicopathologic features and BRAF mutational status were analyzed and correlated with the site of origin of the mPTC in a multicenter cohort of 298 mPTCs from six Italian medical institutions. Tumors arise at a median distance of 3.5 mm below the surface of the thyroid gland. Statistical analysis identified four distinct clusters. Group A, mPTC: size &ge, 5 mm and distance of the edge of the tumor from the thyroid capsule = 0 mm, group B, mPTC: size &ge, 5 mm and distance of the edge of the tumor from the thyroid capsule &gt, 0 mm, group C, mPTC: size &lt, and group D, mPTC: size &lt, 0 mm. Univariate analysis demonstrates significant differences between the groups: Group A shows the most aggressive features, and group D the most indolent ones. By multivariate analysis, group A tumors are characterized by tall cell histotype, BRAF V600E mutation, tumor fibrosis, aggressive growth with invasive features, vascular invasion, lymph node metastases, and intermediate ATA risk. The mPTC clinicopathologic features vary according to the tumor size and distance from the thyroid surface. A four-group model may be useful for risk stratification and to refine the selection of nodules to be targeted for fine needle aspiration.

We sought to investigate the prognostic significance of prodromal angina (PA) in unselected patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and its additive predictive value to the GRACE score. We prospectively enrolled 3015 consecutive STEMI patients undergoing PPCI. Patients were divided in 2 groups according to the presence or absence of PA. Multivariable Cox regression was used to establish the relation to 2-year cardiac mortality of PA. The mean age of the study population was 68 (±14) years; 2178 patients (72%) were male. During follow-up, 395 (13%) patients died with 278 of these (9.2%) suffering from cardiac mortality. Kaplan-Meier estimates showed a survival rate of 95% and 87% for patients with PA and no PA, respectively (log rank test

Objective Malignant aortic tumors (MATs) are exceedingly rare, and a comprehensive review of clinical and therapeutic aspects is lacking in the literature. The aim of this study was to analyze all known cases of MATs and to identify predictors of patients' survival. Methods All patients diagnosed with an aortic tumor treated in a single center along with all case reports and reviews available in the literature through a specific PubMed search using keywords such as “malignant” and “aorta” or “aortic,” “tumor,” or “sarcoma” or “angiosarcoma” were analyzed. The tumor's primary location, clinical presentation, histologic subtype, and treatment choice were examined. Survival at 1 year, 3 years, and 5 years and the possible preoperative and operative outcome predictors were evaluated using Kaplan-Meier analysis with a log-rank test and by Cox regression for multivariate analysis. Results In addition to the 5 cases treated in our center, 218 other cases of MAT were reported in the literature from 1873 to 2017. The mean age of the patients was 60.1 ± 11.9 years, and the male to female ratio was 1.59:1. The median overall survival from diagnosis was 8 (7-9) months; 1-, 3-, and 5-year survival rates were 26%, 7.6%, and 3.5%, respectively. Chronic hypertension (P = .03), fever (P = .03), back pain (P = .01), asthenia (P = .04), and signs of peripheral embolization (P = .007) were significant predictors of a poor result. Histologic subtypes had a different impact on survival, with no statistical significance. Compared with other treatment strategies, combined surgical-medical therapy had the best impact on the median survival rate (surgical-medical, 12 [8-24] months; medical, 8 [5-10] months; surgical 7 [2-16] months; no treatment, 2 [0.5-15] months; P = .001). Analyzing exclusively medical approaches, chemotherapy and radiotherapy had the best impact on median survival rate compared with untreated patients (chemotherapy-radiotherapy, 18 [10-26] months; radiotherapy, 16 [8-20] months; chemotherapy, 10 [7-24] months; no medical treatment, 6 [2-16] months; P = .005); these data were not sustained by multivariate analysis. Conclusions Aortic tumors are a malignant pathologic condition with a short survival rate after initial diagnosis. Survival is further diminished in the presence of clinical factors such as hypertension, fever, back pain, asthenia, and signs of peripheral embolization. Combined surgical and medical treatment, particularly with chemotherapy and radiotherapy, has shown the highest survival rate.

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.

Objectives To define the incidence of vascular complications (VC) after balloon aortic valvuloplasty (BAV) in recent years, and to compare the performance of two vascular closure devices (VCD). Background VC remain the most frequent drawback of BAV and are associated with adverse clinical outcomes. Methods All BAV procedures performed at 2 high-volume centers over a 6-year period (n = 930) were collected in prospective registries and investigated to assess the incidence of Valve Academic Research Consortium-2 (VARC-2) defined VC. Incidence of life-threatening, major and minor bleeding was also assessed. In-hospital major adverse cardiac and cerebrovascular events (MACCE) rate (composite of in-hospital death, myocardial infarction, TIA/stroke, and life-threatening bleeding) as well as 30-day survival was compared between a suture-mediated closure system and a collagen plug hemostatic device. Results A 9 Fr arterial sheath was used in most of the patients (84.1%). Vascular closure was obtained with the Angio-Seal in 643 patients (69.1%) and the ProGlide in 287 (30.9%). The overall incidence of major VC was 2.7%, and minor VC 6.6%, without significant differences between groups. The Angio-Seal group was associated with a higher rate of small hematomas (6.9% vs. 3.5%, P = 0.042), whilst blood transfusions were more frequent in the ProGlide group (6.6% vs. 3.5%, P = 0.034). Rates of in-hospital MACCE and 30-day survival were similar. Use of either VCD was not independently associated with major VC. Conclusions VC rate after BAV is fairly low in experienced centers without major differences between the 2 most used VCD.

Background Infectious complications represent one of the main causes of perioperative morbidity and mortality of liver transplant recipients. The primary objective of this retrospective observational study was to evaluate incidence and etiology of early (within 1 month from surgery and occurring in the intensive care unit [ICU]) postoperative infections as well as donor- and recipient-related risk factors. Methods The data of 280 patients undergoing 299 consecutive liver transplant procedures from January 2012 to December 2015 were extracted from the Italian ICU registry database and hospital registries. Perioperative risk factors, etiology of infections, and antibiotic susceptibility of isolated microorganisms were taken into consideration. Results Global incidence of postoperative infections was 21%. Pneumonia was the most frequent infection and, globally, gram-negative bacteria were the most common agents. Septic shock was present in 22% of infection cases and hospital mortality was higher in patients with postoperative infection. Preoperative chronic obstructive pulmonary disease, malnutrition, preoperative ascites, encephalopathy, and early re-transplantation were significantly associated to post orthotopic LT infections. Conclusion Infections represent a major cause of early postoperative morbidity and mortality. The impact of single risk factors and the results of their preoperative management should be further investigated in order to reduce the incidence and evolution of postoperative infections.

Objective To determine, in patients with ST-segment Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the prognostic weight of cardiac arrest (CA) according to the type of rhythm (shockable vs. non-shockable). Methods We prospectively enrolled 3278 consecutive STEMI patients undergoing PPCI. Multivariable Cox regression was used to establish the relation to 1-year cardiac mortality of both type of CA. In patients suffering from CA we identified predictors of both poor neurological outcome (cerebral performance categories 3–5) and cardiac mortality at 1 year. Results The incidence of CA was 7.26% (n = 238). Of these, 196 (5.98%) had an initial shockable rhythm and 42 (1.28%) a non shockable rhythm. During 1-year follow up 311(9.48%) patients died from cardiac causes. Shockable rhythm (adjusted-HR = 1.61; 95%CI 1.08–2.43, p = 0.02) and non-shockable rhythm (adjusted-HR = 3.83; 95%CI 2.36–6.22, p < 0.001) were independently associated with 1-year cardiac mortality. Among patients with CA those with shockable rhythm had a lower risk of poor neurological outcome at 1 year follow up (adjusted OR = 0.22: 95%CI; 0.08–0.55, p = 0.001). Independent predictors of 1-y cardiac mortality were: non shockable rhythm (adjusted HR = 2.6; 95%CI; 1.48–4.5, p = 0.001), crew-witnessed CA, diabetes mellitus, left ventricle ejection fraction and creatinine on admission. There was a significant interaction between type of rhythm and crew-witnessed CA (p = 0.026). Conclusions In patients with STEMI undergoing PPCI patients with both shockable and non shockable CA are at increased risk of 1-year cardiac mortality. Among patients with CA those with non shockable rhythm have an higher risk of both poor neurological outcome and cardiac mortality at 1 year.