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Background: 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. Aims: 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. Methods: The performance of several prognostic scores was assessed through a Cox regression-model evaluating the C-index and the Akaike Information Criterion (AIC). Results: 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

Survival and exercise performance are key targets of heart transplantation (HT). We designed this study to help in identifying (1) patients with chronic heart failure (CHF) at risk of poor exercise capacity after HT and (2) HT recipients presenting risk factors modifiable with exercise showing a potential impact on outcome. We enrolled 49 HT recipients (age 52 ± 12 years, 84% males) who underwent a cardiopulmonary exercise test before (9 ± 6 months) and after (20 ± 14 months) HT. In the CHF phase, lower peak oxygen consumption (V̇O 2) (odds ratio 0.69, P=0.017) independently predicted peak V̇O 2 improvement after HT. In the post-HT phase, body mass index (BMI) [adjusted hazard ratio (HR) 1.16, P=0.034] and V̇E (ventilation)/V̇CO 2 (carbon dioxide production) slope (adjusted HR 1.07, P=0.031) independently predicted mortality. In conclusion, CHF patients with only a moderate impairment of peak V̇O 2 are at a risk of failing to achieve a significant improvement of exercise performance after HT. In the post-HT phase, a BMI≥28 and/or a V̇E/V̇CO 2 slope ≥47 represent risk factors for death, which are potentially modifiable with exercise. Prospective randomized studies are needed to analyze the effects of training on functional capacity and outcome in the different subsets of HT recipients.

Several biomarkers have been proposed as useful parameters to better specify the prognosis or to delineate new target therapy strategies for glioblastoma patients. MicroRNAs could represent putative target molecules, considering their role in tumorigenesis, cancer progression and their specific tissue expression. Although several studies have tried to identify microRNA signature for glioblastoma, a microRNA profile is still far from being well-defined. In this work the expression of 19 microRNAs (miR-7, miR-9, miR-9∗, miR-10a, miR-10b, miR-17, miR-20a, miR-21, miR-26a, miR-27a, miR-31, miR-34a, miR-101, miR-137, miR-182, miR-221, miR-222, miR-330, miR-519d) was evaluated in sixty formalin-fixed and paraffin-embedded glioblastoma samples using a locked nucleic acid real-time PCR. Moreover, a comparison of miRNA expressions was performed between primary brain neoplasias of different grades (grades IV-I). The analysis of 14 validated miRNA expression in the 60 glioblastomas, using three different non-neoplastic references as controls, revealed a putative miRNA signature: mir-10b and miR-21 were up-regulated, while miR-7, miR-31, miR-101, miR-137, miR-222 and miR-330 were down-regulated in glioblastomas. Comparing miRNA expression between glioblastoma group and gliomas of grades I-III, 3 miRNAs (miR-10b, mir-34a and miR-101) showed different regulation statuses between high-grade and low-grade tumors. miR-10b was up-regulated in high grade and significantly down-regulated in low-grade gliomas, suggesting that could be a candidate for a GBM target therapy. This study provides further data for the identification of a miRNA profile for glioblastoma and suggests that different-grade neoplasia could be characterized by different expression of specific miRNAs.

SummaryMean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1

Background: The number of indications for strictureplasty for Crohn’s disease has been greatly reduced since the widespread use of biologics, although the risk of intestinal failure remains. The aim of the study was to analyze the outcomes of strictureplasty and to identify risk factors for site-specific recurrence in the era of biologics. Methods: Consecutive patients treated with strictureplasty for Crohn’s disease between 2002 and 2018 were retrospectively included. Univariate analysis was carried out. Risk factors for recurrence were identified through a multilevel logistic regression analysis. Results: Two hundred sixty-six patients were included in the study (171 males, median age 39.5years, range 18–76years). The majority of the 718 strictures requiring surgery in these patients were located in the ileum (61%), treated with conventional strictureplasty (89.6%) and required an additional resection (73.7%). Median follow-up time and time to recurrence were 96months and 62.5months respectively. The site-specific recurrence rate was 12.2% at 5years and 25.7% at 10years. Smoking was associated with a higher risk of recurrence in patients with milder disease. The 10-year recurrence rate was significantly higher for strictureplasties performed in the terminal ileum (30.9%, p = 0.0019) as compared to the ileum (21.8%) and the jejunum (8.4%). Multilevel logistic regression analysis showed that postoperative exposure to biologics (OR 4.74, p 0.001), nonconventional strictureplasty (OR 3.57, p 0.008) and a strictureplasty performed on a previous anastomosis (OR 13.58, p 0.002) were associated with site-specific recurrence. Conclusions: Strictureplasty is associated with optimal long-term outcomes in the biologic era and should be performed when feasible, to reduce the risk of intestinal failure in Crohn’s disease patients.

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.

Background Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. Objective The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. Methods Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. Results Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. Conclusions Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

Dronedarone was found to have divergent safety profiles in randomized controlled trials (RCT) in term of cardiac death and overall mortality. We decided to evaluate all available evidence on the cardiovascular safety of this drug. A systematic search was made of the MEDLINE and the Cochrane Central Register of Controlled Trials from January 2003 through April 2016 for RCT comparing dronedarone to placebo/active control, to provide the most accurate estimate of the effects of this agent and observational cohort studies (OBS) reporting clinical outcomes in patients treated with dronedarone, according to current guidelines, to obtain a real-life comparator for the findings summarized by RTC analysis. The literature search yielded 2335 papers and after careful review we identified 12 RCT and 7 OBS studies. RCT meta-analysis showed that, despite high heterogeneity, dronedarone was not associated with increased all-cause mortality [OR (Odds Ratio) 1.36, 95%CI (Confidence Interval) 0.79-2.33; p=0.732, I2=57.0%] or cardiovascular mortality [OR 1.51 95%CI 0.74-3.08; p=0.860, I2=64.4%]. OBS studies had a trend toward a better survival with respect to RCT [ES (Effect Size) 2.03, 95%CI 0.53-3.53 vs. ES 3.03, 95%CI 1.23-4.83; p=0.115], reaching the significance when restricted to the cardiovascular mortality [ES 0.52, 95%CI 0.36-0.69 vs. ES 1.86, 95%CI 0.62-3.09; p

ABSTRACT: Aim: To evaluate if anti-Müllerian hormone (AMH) is a reliable marker of ovarian reserve in young women undergoing ovarian tissue cryopreservation. Patients & methods: Relationships of serum AMH levels with primordial follicle density, age and reproductive hormones were investigated using the Pearson or Spearman correlation coefficient in 86 women with cancer (12–38 years) undergoing ovarian tissue cryopreservation. AMH variations through the menstrual cycle were assessed by the Kruskal–Wallis test. p

AimsThis study compared the clinical, functional, and haemodynamic characteristics and current era survival of subgroups of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD): Eisenmenger syndrome (ES); PAH-CHD associated with systemic-to-pulmonary shunts (SPs); PAH with small defects (SDs); and PAH after defect correction (CDs).Methods and resultsData from consecutive PAH-CHD patients referred to our centre from 1 January 1998 to 31 May 2011 were collected. A contemporary group of idiopathic PAH patients was utilized for comparison. Treatment was per PAH guidelines, including combination therapy, with approved PAH-specific drugs. Survival was assessed with Kaplan-Meier analysis from the first invasive haemodynamic confirmation of PAH and compared across subgroups by log-rank test. Of 192 patients (mean age 41 ± 17 years; 61% female), 90 had ES (aged 41 ± 16 years); 48 SP (aged 47 ± 18 years); 10 SD (aged 25 ± 21 years); and 44 CD (aged 36 ± 17 years). Patients with ES had the highest baseline pulmonary vascular resistance and the lowest exercise capacity. Seventy-eight per cent were treated with approved PAH-specific drugs, and 44% were treated with combination therapy. Kaplan-Meier survival estimates (95% confidence interval) at 20 years for ES, SP, and CD were 87% (77-93%), 86% (60-96%), and 36% (12-72%, P = 0.0001 vs. ES; P = 0.004 vs. SP), respectively, and at 15 years for SD was 66% (16-91%, P = 0.015 vs. ES; P = 0.016 vs. SP). The survival of the 278 patients with idiopathic PAH appeared to be worse when compared with the PAH-CHD subgroups.ConclusionRelevant clinical, functional, haemodynamic, and survival differences were observed among subgroups. In particular, patients with CD and SD had the worst survival. These findings should be considered when planning medical or interventional treatment strategies in PAH-CHD patients.

BACKGROUND:There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood.METHODS:A prospective, cohort study was conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003–2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status.RESULTS:The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GBS at the rectovaginal site. Early (7–30 days) LOD presentation was associated with neonatal brain lesions or death (odds ratio: 0.96 [95% confidence interval: 0.93–0.99]). Intrapartum antibiotic exposure was significantly associated with mild (12 of 22) rather than severe (11 of 45; P = .03) LOD.CONCLUSIONS:Preterm neonates had the highest rates of LOD and mortality. Most mothers carried GBS at the time of the LOD diagnosis, whereas 6% had mastitis. Intrapartum antibiotics were associated both with delayed presentation of symptoms and milder LOD.

Objectives To correlate the severity of lung neovascularity (Sheehan vessels) with the cause and haemodynamic severity of pulmonary arterial hypertension (PAH), pulmonary artery (PA) size and heart disease type in patients with PH associated with congenital heart diseases (PAH-CHD) and idiopathic PH (IPAH). Methods We reviewed the HRCT and CT pulmonary angiography studies of 87 patients with PAH-CHD and 111 with IPAH; all had undergone right heart catheterisation. We evaluated the PA size and severity of neovascularity on CT. Results Neovascularity, which was found in 72% of PAHCHD (56% with Eisenmenger's syndrome) and in 22%of IPAH patients, is significantly related to the severity of PH and all patients with severe neovascularity had intermediate or high PH. All PAH-CHD patients had a dilated PA with a greater risk of developing severe dilatation (diameter >5 cm). The neovascularity correlated with the PA size only in IPAH. Conclusions Neovascularity even if not pathognomonic for PAH-CHD, is significantly more common in these patients, especially in Eisenmenger's syndrome. It is often the first CT sign to indicate the severity of PH in PAH-CHD and IPAH. A neovascularity ≥5 on CT indicates a intermediate or high PH. Key Points • Large retrospective studying specific lung disorders in patients with pulmonary arterial hypertension. • Neovascularity is often the first CT sign indicating the severity of pulmonary hypertension Alterations of lung parenchyma on CT in pulmonary hypertension are described • The first study to assess the severity of pulmonary hypertension by CT • If substantiated, CT might eventually replace some cardiac catheterisation for evaluating PH

Aims Many inoperable patients with severe aortic stenosis (AS) are not immediately eligible for transcatheter aortic valve implantation (TAVI). We evaluated the role of percutaneous balloon aortic valvuloplasty (BAV) in this setting. Methods and results Among 210 consecutive patients referred to our institution for BAV, we identified three groups: immediately eligible for TAVI (n=65, 31%), excluded from TAVI (n=67, 32%), BAV as a bridge to TAVI (n=78, 37%). This last group comprised patients with low left ventricular ejection fraction, frailty or enfeebled status, symptoms of uncertain origin, critical conditions, moderate-to-severe mitral valve regurgitation, need of major non-cardiac surgery. Outpatient clinic visit and echocardiography were performed around one month after BAV to decide the final therapeutic strategy. Mean age was 81±8 years and the vast majority of patients had comorbidities and high-risk features. The incidence of periprocedural adverse events was 6.4%: 5.1% death (four patients: one procedural complication, three, natural disease progression), 1.3% minor stroke. After BAV, 46% of these patients were deemed eligible for TAVI, and 28% for cardiac surgery. Patients who underwent TAVI after bridge BAV showed 94% 30-day survival. Conclusions BAV is a safe and effective tool to bridge selected patients to TAVI when indications are not obvious.

Aims Treatment delay is a powerful predictor of survival in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We investigated effectiveness of pre-hospital diagnosis of STEMI with direct referral to PCI, alongside more conventional referral strategies. Methods and results From January 2003 to December 2004, 658 STEMI patients were referred for primary PCI at our intervention laboratory. Three predefined referral routes were compared: (1) for patients within 90 min drive of the PCI centre, pre-hospital diagnosis and direct transportation ( n =166), (2) diagnosis at the interventional hospital emergency department ( n =316), (3) diagnosis at local hospitals before transportation ( n =176). Pre-hospital diagnosis was associated with more than 45 min reduction in treatment delay ( P =0.001). No significant difference in in-hospital mortality was apparent in the overall study population. In the cardiogenic shock subgroup ( n =80), pre-hospital diagnosis was associated with a two-thirds reduction in in-hospital mortality ( P =0.019); mortality was only 6.2% in shock patients who underwent PCI in

End-stage hypertrophic cardiomyopathy (ES-HC) has an ominous prognosis. Whether genotype can influence ES-HC occurrence is unresolved. We assessed the spectrum and clinical correlates of HC-associated mutations in a large multicenter cohort with end-stage ES-HC. Sequencing analysis of 8 sarcomere genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1) and 2 metabolic genes (PRKAG2 and LAMP2) was performed in 156 ES-HC patients with left ventricular (LV) ejection fraction (EF)

Saber-sheath trachea is a specific radiographic parameter for chronic obstructive pulmonary disease (COPD), which consists of marked coronal narrowing associated with sagittal widening (tracheal index 2/3-0.67). The aim of this study was to investigate the correlation between saber-sheath trachea and clinical-radiological findings in a group of patients with COPD of varying severity.We evaluated the chest radiographs of 71 patients with COPD distributed as follows: GOLD class I, 8/71 (11.3 %); class II, 34/71 (47.9 %); class III, 16/71(22.5 %); class IV, 13/71 (18.3 %). In 52/71 (73.2 %) patients we also evaluated chest computed tomography (CT) scans. We analyzed the prevalence of saber-sheath trachea and its correlation with the Tiffenau index, GOLD stage and radiological signs of COPD. Moreover, we evaluated the sensitivity, specificity and accuracy of chest radiography as compared to CT taken as the gold standard, and the correlation between the radiographic and CT tracheal index.Saber-sheath trachea was found in 18/71 (25.4 %) patients, with a greater prevalence in patients with lower Tiffenau Index (p = 0.02), GOLD stages III-IV and visual severity score 3 (severe) on chest CT. Saber-sheath trachea was not found to be related to other radiological signs of COPD. The sensitivity, specificity and accuracy values of radiography were 72.2, 97.0 and 88.5 %, with perfect concordance between the radiographic and CT tracheal index (p 0.00001).Saber-sheath trachea is linked to the functional severity of airway obstruction, but not to other radiological signs of COPD. Thus, evaluation of the trachea at chest radiography is strongly recommended.

Chronic Obstructive Pulmonary Disease (COPD) represents a major health concern, that causes a significant morbidity, a high risk of death and important health-care costs. The real dimension of this chronic disease is probably understimated both in its early and advanced stages and its prevalence is progressively rising in the general populations, because of both increase of elderly subjects and raised rates of smoke. To date it was estimated that COPD-related deaths represent the sixth leading cause of mortality worldwide. Acute exacerbations (AE) represent major events in the clinical course of COPD and negatively affect its outcomes, leading to lung function decrease, quality life worsening, high risks of hospital readmission, disability and death. Severe exacerbations of COPD are associated with acute respiratory failure (ARF), impairment of hypoxemia, various degree of carbon dioxide retention and acidosis. The ARF in COPD may occur as acute, chronic or acute-on-chronic failure. This condition worsens significantly the prognosis of these patients and may require an intensive treatment with ventilatory assistance combined with routine medical management. This therapeutic approach may be performed by means of invasive (IMV) or noninvasive mechanical ventilation (NIMV). The latter form is defined as the delivery of mechanical ventilation that avoids airway invasion. Two types of NIMV have been studied and applied to clinical practice in the last decades, they are represented by both external negative pressure and positive pressure ventilation modalities. In the last years noninvasive mechanical ventilation with positive pressure (NPPV) has been increasingly used as adjunctive therapeutic approach in these subjects. In addition several controlled trials and meta-analysis showed that this form of assisted ventilation is effective in the treatment of different diseases, including: COPD exacerbations, acute cardiogenic pulmonary edema, weaning from ventilator in COPD patients. The use of noninvasive mechanical ventilation in patients with COPD exacerbated and hypercapnic ARF is associated, in some instances, with a decreased need of endotracheal intubation, with lower incidence of adverse outcomes, as well as with reduced in hospital-mortality, length of hospitalisation and overall costs. This therapeutic approach is generally feasible, well-tolerated and may be successfully performed in different healthcare settings including: Emergency Departments, Intensive Care Units (ICUs), but also in Intermediate Respiratory Care Units (IRCUs) and, in selected cases, in non intensive units, such as General Wards. This report is a comprehensive review of the available studies, concerning the use of NIMV in the management of COPD patients with AE and respiratory failure and it describes its indications, limitations, proper locations and costs

Introduction: Recent immunological assays based on the measurement of released interferon-gamma after stimulation of T-cell responses with Mycobacterium tuberculosis specific antigens (IGRAs) have been developed for the immunodiagnosis of latent tuberculosis infection (LTBI). A major concern about the use of IGRAs in children regards the possibility of higher frequency of indeterminate results, because their immune system can still be immature. Aim of this study was to evaluate the frequency of indeterminate results in children and their possible association with diagnosis. Methods: We retrospectively evaluated the routine use of Quantiferon-TB Gold In-Tube (QFT-IT; Cellestis, Australia) on 445 children at the Pediatric Pneumology Unit of S. Orsola-Malpighi General Hospital during the period April 2007-August 2012. Patients were divided by age groups as follows: < 2 years old (n=122), 2-5 years old (n=151), 5-10 years old (n=126) and 10-17 years old (n=66). Results: In our pediatric population: mean age was 5.4 ± 3.9 years, 246 (55%) were male, 99 (22%) were not Italy-born, 179 (40%) were born in Italy from immigrant families and 167 (38%) were Italian. QFT-IT was positive in 70 (16%) children, negative in 353 (79%) and indeterminate in 22 (5%). All indeterminate QFT-IT results in this study were due to an inadequate response to PHA; 3 patients had a known iatrogenic immunosuppression. Indeterminate results were not statistically distributed among different age groups (p=0.386). Diagnosis was available in 321 (72%) children: 30 (9%) were diagnosed as LTBI, 38 (12%) as active TB, 34 (11%) as pneumonia, 219 (68%) were exposed to a TB case. Indeterminate QFT-IT results were distributed as follows: 0% in LTBI, 0% in active TB, 0.5% in exposed to a TB case and 23.5% in pneumonia. A statistically association with diagnosis of pneumonia was observed (p=0.0001). Conclusion: These preliminary data suggest that age hasn’t effect on frequency of indeterminate QFT-IT results, supporting the use of this immunological test in young children. In our population pneumonia seems a risk factor associated with indeterminate QFT-IT. Immunological anergy due to pneumonia should been further investigated.

Objectives: To investigate the prognostic significance of baseline white blood cell count (WBCc) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and its additive predictive value beyond the Global Registry of Acute Coronary Events (GRACE) score. Methods: We included 1,315 consecutive NSTE-ACS patients. Patients were divided in quartiles according to the WBCc (cells per 1 mm3) i.e. Q1 Results: The median age of the study population was 76 years. Overall, 335 patients (25.5%) died with 211 of these (16%) suffering from CVD. Patients in Q4 showed a higher cumulative probability of CVD compared to patients in Q1–Q3. On multivariable analysis, patients in Q4 were at higher risk of CVD [hazard ratio (HR) = 1.47, 95% confidence interval (CI) 1.09–1.98, p = 0.011]. WBCc as a continuous variable was also independently associated with the study end point (HR = 1.043; 95% CI 1.02–1.07; p = 0.001). However, the incorporation of WBCc into the GRACE score did not improve either prediction of risk (C-index = 0.796 for GRACE score with or without WBCc) or classification of risk [relative integrated discrimination improvement = 0.0154, 95% CI) –0.029 to 0.0618; continuous net reclassification improvement = –0.0676, 95% CI –0.2149–0.0738). Conclusions: WBCc was an independent predictor of 3-year CVD in patients with NSTE-ACS. However, it did not add prognostic information beyond the GRACE score.

Aim Randomized controlled trials (RCTs) showed that biventricular (BiV) pacing reduces heart failure (HF) hospitalizations and mortality in patients with New York Heart Association (NYHA) class III–IV HF, left ventricular (LV) dysfunction, and wide QRS. We performed a systematic review and meta-analysis of the RCTs comparing LV-only vs. biventricular (BiV) pacing in candidates for cardiac resynchronization therapy (CRT). Methods and results The systematic review selected five RCTs (out of 1888 analysed reports) with a cumulative number of 372 patients randomized to BiV pacing and 258 to LV-only pacing. The meta-analysis shows that BiV pacing is not superior to LV-only pacing and that these two pacing modalities do not differ with regard to death or heart transplantation [LV-only vs. BiV pacing odds ratio (OR) 1.24, 95% confidence interval (CI) 0.57–2.70 with the fixed effect model, OR 1.25, 95% CI 0.48–3.24 with the random effect model]. Specific data on hospitalizations were available only in two RCTs with a cumulative number of 127 patients randomized to BiV and 123 to LV-only pacing. The meta-analysis shows that BiV pacing is not superior to LV-only pacing and that these two pacing modalities do not differ with regard to this outcome (LV-only vs. BiV pacing OR 0.86, 95% CI 0.49–1.50 with the fixed effect model, OR 0.86, 95% CI 0.49–1.50 with the random effect model). Conclusions Biventricular pacing is not superior to LV-only pacing, and these two pacing modalities appear to achieve similar efficacy in candidates for CRT for moderate to severe HF, in terms of all-cause mortality and hospitalizations during follow-up.

Background & Aims The hepatic vein pressure gradient (HVPG) is the standard used to determine the degree of portal hypertension (PH) and an important prognostic factor for patients with cirrhosis; HVPG values correlate with the presence of esophageal varices (EV). However, HVPG can only be accurately determined at specialized centers; noninvasive methods are needed to predict HVPG values and the presence of EV. We compared the diagnostic performance of spleen stiffness (SS) measurement by transient elastography with that of liver stiffness (LS) and of other recently proposed noninvasive tests. Methods We measured SS and LS in 100 consecutive patients with hepatitis C virus–induced cirrhosis. Patients were also assessed by FibroScan, HVPG, esophagogastroduodenoscopy, and liver biopsy. We also analyzed LS–spleen diameter to platelet ratio score and platelet count to spleen diameter. Results SS and LS were more accurate than other noninvasive parameters in identifying patients with EV and different degrees of PH. A linear model that included SS and LS accurately predicted HVPG values ( R 2 = 0.85). The results were internally validated using bootstrap analysis. Conclusions Measurement of SS can be used for noninvasive assessment and monitoring of PH and to detect EV in patients with hepatitis C virus–induced cirrhosis.

Background. Congenital diaphragmatic hernia (CDH) still has a high mortality despite advanced assistance techniques. The aim of this study is to verify the validity of fve respiratory and blood-gas-derived indices in defining presurgical stabilization: the oxygenation index (OI), the alveolar-arterial O2 gradient (A-aDO2), the arterial-alveolar O2 tension ratio (a/AO2), the arterial pH and the PaCO2. Methods. The study involved 73 neonates with CDH where the accuracy of stabilization was assessed through the survival percentage and the contemporary behaviour of mean arterial pressure (MAP), ductal shunting, urine output and lactate levels. The trend of the indices was compared in two groups (stable/ft for surgery vs unstable/unfit for surgery) at five times (PICU admission, 6, 12, 24 hours after admission, assessment of clinical stabilization). Results. Fifty-fve neonates were defined stabilized on the basis of the indices and underwent surgery with a 100% survival rate; 18 patients died before surgery, having never achieved clinical stabilization. MAP, ductal shunting, urine output and lactate levels were normal in the stabilized patients and altered in the non stabilized. Of the fve parameters considered, all three oxygenation-linked indices (OI, A-aDO2, a/AO2) are very powerful, whereas pH and PaCO2 appears valid but more tardive. Their progressive improvement (OI0.50, PaCO27.35) defined presurgical stabilization, thus allowing CDH surgical correction. Conclusion. The study confirms the validity of these indices as a guide to the treatment of neonates with CDH, showing a good reliability in identifying presurgical stabilization

Background. The study aims to verify if the time of preoperative stabilization (≤24 or >24 hours) could be predictive for the severity of clinical condition among patients affected by congenital diaphragmatic hernia.Methods. 55 of the 73 patients enrolled in the study achieved presurgical stabilization and underwent surgical correction. Respiratory and hemodynamic indexes, postnatal scores, the need for advanced respiratory support, the length of HFOV, tracheal intubation, PICU, and hospital stay were compared between patients reaching stabilization in ≤24 or >24 hours.Results. Both groups had a 100% survival rate. Neonates stabilized in ≤24 hours are more regular in the postoperative period and had an easier intensive care path; those taking >24 hours showed more complications and their care path was longer and more complex.Conclusions. The length of preoperative stabilization does not affect mortality, but is a valid parameter to identify difficulties in survivors’ clinical pathway.

The aim of this study was to assess the baseline computed tomography (CT) attenuation of acute and chronic pulmonary thromboemboli, their contrast enhancement (CE), correlation with haematocrit (Ht) levels and the presence of hypertrophic bronchial arteries. From January 2006 to October 2009, we measured the baseline and postcontrast attenuation values of acute pulmonary thrombi emboli on CT angiograms of 86 patients with acute pulmonary embolism (PE) and those of chronic thrombi in 29 patients with pulmonary hypertension of various origins. The attenuation of acute thrombi was correlated with Ht and CE of chronic thrombi with the presence of hypertrophic bronchial arteries. Acute emboli had a mean baseline attenuation of 54.9 Hounsfield units (HU) and showed no CE. The attenuation of acute thrombi was not dependent on Ht. Chronic thrombi had a mean baseline attenuation of 33.8 HU, and 54% of thrombi showed significant CE. In 57% of cases, a collateral circulation had developed. In 76.5% of cases, CE and hypertrophic bronchial arteries coexisted (p=0.026). Neither thrombotic CE nor bronchial artery hypertrophy predominated in any one of the diseases associated with chronic thrombosis. Before contrast administration, acute emboli coare prevalently hyperattenuating and therefore more conspicuous. Only chronic thrombi exhibit CE, and CE is significantly associated with the development of collateral circulation, which may be involved in the process of thrombotic recanalisation.

Senile systemic amyloidosis (SSA) is a cardiomyopathy mainly affecting elderly men due to intramyocardial deposition of wild-type (nonmutant) transthyretin (TTR) ([1][1]). Since the heart is the only involved organ, SSA—which requires endomyocardial biopsy (EMB) for a definite diagnosis—is often

Objectives: In a cohort of patients with hereditary transthyretin-related amyloidosis (ATTR), we aimed to assess the role of 99mTc-3,3- diphosphono-1,2-propanodicarboxylic acid ( 99mTc-DPD) in detecting myocardial amyloid infiltration across a wide spectrum of cardiac involvement and in predicting major adverse cardiac events (MACE). Background: Hereditary transthyretin-related amyloidosis is a challenging and underdiagnosed condition where both early diagnosis and prognosis remain problematic. Methods: We evaluated 63 patients with ATTR: 40 with and 23 without echocardiographically diagnosed amyloidotic cardiomyopathy (AC). Myocardial uptake of 99mTc-DPD scintigraphy was semiquantitatively and visually assessed at 5 min and 3 h. Results: All patients with AC showed moderate-to-severe myocardial tracer uptake (i.e., visual score 12 mm in combination with H/WB >7.5 was associated with the highest event rate. Conclusions: In ATTR, 99mTc-DPD scintigraphy can identify myocardial infiltration across a wide spectrum of morphologic/functional cardiac involvement, allowing an early diagnosis of the disease (even before the appearance of echocardiographic abnormalities). The 99mTc-DPD myocardial uptake is a prognostic determinant of "cardiac" outcome in ATTR, either alone or in combination with LV wall thickness

Purpose. Evaluation of computed tomography (CT) pulmonary angiography parameters revealing pulmonary embolism (PE) severity with particular attention to pulmonary obstruction indexes. Comparison with clinical and hemodynamic data and determination of predictive role in the development of chronic pulmonary heart disease. Materials and methods. This retrospective study analyzes 45 not consecutive patients from November 2007 to December 2008 with CT angiography diagnosis of acute PE. Included in the study are patients at the first documented episode of acute PE, with 6 month follow-up. Patients with severe pre-existent cardiopulmonary pathology or neoplastic diseases were excluded from the study. CT angiography evaluated right ventricular (RV)/left ventricular (LV) ratio, obstruction index according to Qanadli and Total Clot Burden (Ghanima score). PE indexes were compared with Troponin I measurement and echocardiography result; at last hospitalization and intensive care time were reported. Results. A significant association was found between Ghanima and Qanadli score: the two indexes are equivalent in quantification of pulmonary arterial obstruction (p

Aims There is no cure for pulmonary arterial hypertension, but current approved treatment options include prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5 inhibitors. The effect on survival of these compounds has not been appropriately assessed in individual trials because of small sample size and short duration. We performed a meta-analysis of all randomized controlled trials with drugs published in this condition. Methods and results Trials were searched in the Medline database from January 1990 to October 2008. The primary analysis included only studies with a placebo comparator arm, the sensitivity analysis also included studies comparing two active treatment arms. The main outcome measure was all-cause mortality. Twenty-one trials were included in the primary analysis (3140 patients) and two additional studies (59 patients) were included in the sensitivity analysis. Average duration of the trials was 14.3 weeks. All-cause mortality rate in the control group was 3.8%. Active treatments were associated with a reduction in mortality of 43% (RR 0.57; 95% CI 0.35–0.92; P = 0.023); the sensitivity analysis confirmed a reduction in mortality of 38% (RR 0.62; 95% CI 0.39–1.00; P = 0.048). Conclusion The results of this meta-analysis suggest an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension.

We investigated the impact of ambulance-based prehospital triage on treatment delay and all-cause mortality (in hospital and long term) in patients with ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock referred for primary percutaneous coronary intervention in a prospectively collected registry. During the study period (January 2003 to December 2005), a total of 121 patients was referred for primary percutaneous coronary intervention at our intervention laboratory through 2 main triage groups: (1) after prehospital, ambulance-telemedicine-based triage (42 patients) and (2) by more conventional routes (79 patients) represented by the institutional S. Orsola-Malpighi hospital emergency department triage (44 patients) and spoke hospital triage (35 patients). Total ischemic time was shorter in the prehospital triage (142 minutes, range 106 to 187, vs 212 minutes, range 150 to 366, p = 0.003). Patients with prehospital triage showed a lower rate (29% vs 54%, p = 0.01) of severely depressed (

Background High mortality rates were reported in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary interventions (PPCI) "off-hours." The objective of this study was to evaluate this issue in a more recent population of patients with STEMI treated with PPCI in a high-volume tertiary center specifically dedicated to STEMI treatment. Methods and Results We analyzed in-hospital/1-year mortality among 985 consecutive patients with STEMI treated with PPCI between January 2003 and December 2005 in a high-volume (>1400 PCI/year) hub center in a STEMI provincial network organization during "normal-hours" (weekdays 08:00 am to 07:29 pm) and "off-hours" (weekdays 07:30 pm to 07:59 am and weekends). Most (61.2%) patients were treated during "off-hours". Clinical and angiographic characteristics of the "normal-hours" and "off-hours" groups were comparable (in both groups, glycoprotein IIb/IIIa were administered to ∼80% patients). The off-hours group tended toward higher median (25th-75th percentiles) total ischemic time (199 [135-312] minutes vs 179 [126-285] minutes; P = .052). Median electrocardiogram-to-balloon time was less than 90 minutes in both groups. Despite 20 minutes longer median total ischemic time, patients who underwent PPCI during "off-hours" showed similar post-PPCI Thrombolysis In Myocardial Infarction 3 flow grade and mean left ventricular ejection fraction. No difference could be observed between the 2 groups in terms of in-hospital and 1-year mortality rates. Conclusion This study provides evidence that the clinical effectiveness of "normal" and "off-hours" PPCI can be equivalent, at least when performed at a center specifically dedicated to STEMI treatment with frequent use of glycoprotein IIb/IIIa agents.

A knowledge of the predictive factors of the development and persistence of symptoms in gallstone patients (GS) plays a key role in clinical decision making. The aim of this study was to evaluate the presence of predictive factors for biliary pain development in GS, stressing the role of gallbladder motility.A total of 153 (104 women, 49 men) consecutive GS were enrolled. Gallbladder motility (%Emptying [%E], residual volume [RV]) was evaluated by ultrasonography and biliary symptoms were evaluated using a specific questionnaire in all GS at baseline and after 4 yr of follow-up.At enrolment, 61 GS reported recent (GSr) and 31 GS remote (GSo) (2 yr before) episodes of biliary pain, and 61 were asymptomatic (GSa). At baseline, GSr showed a greater %E and a smaller RV than both GSo and GSa (p0.001). After follow-up, biliary pain developed more frequently in GSr (33.3%) than in GSo (16%) and GSa (15%) (p= 0.04). The search for predictive factors of biliary pain development (by univariate and multivariate analyses) revealed a high %E, a small RV, and a history of biliary pain as risk factors.Efficient gallbladder motility is present in symptomatic GS and it represents a risk factor for biliary pain development while sluggish motility seems to play a protective role. Thus, gallbladder motility evaluation is a useful diagnostic tool in clinical decision making for GS; in symptomatic GS, a progressive reduction of gallbladder motility could suggest a "wait and see" management policy instead of an immediate surgical approach.

Summary Background Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved. Aim To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma. Methods One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 ± 1.44 months. Results Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (≤25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), γ-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographyc pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index. Conclusions The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.

AIM: To simultaneously evaluate the presence of defects in gallbladder and gastric emptying, as well as in intestinal transit in gallstone patients (GS) and the effect of chronic ursodeoxycholic acid (UDCA) administration on these parameters and on serum bile acids and clinical outcome in GS and controls (CTR). METHODS: After a standard liquid test meal, gallbla-dder and gastric emptying (by ultrasound), oroileal transit time (OITT) (by an immunoenzymatic technique) and serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR. RESULTS: OITT was longer in GS than in CTR (P < 0.0001); UDCA significantly reduced OITT in GS (P < 0.0001), but not in CTR. GS had longer gastric half-emptying time (t1/2) than CTR (P < 0.0044) at baseline; after UDCA, t1/2 significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration had no effect on gastric emptying and intestinal transit in both GS and CTR. CONCLUSION: The gallstone patient has simultaneous multiple impairments of gallbladder and gastric emptying, as well as of intestinal transit. UDCA administration restores these defects in GS, without any effect in CTR. These results confirm the pathogenetic role of gastrointestinal motility in gallstone disease and suggest an additional mechanism of action for UDCA in reducing bile cholesterol supersaturation.

Aim The spectrum of histological alterations, namely atrial amyloidosis, in the right and left atria of patients with chronic persistent atrial fibrillation (AF) and rheumatic heart disease is not completely known. Methods and results One hundred and twenty-eight atrial appendages (66 left and 62 right), obtained from 72 patients with rheumatic valve disease and chronic AF undergoing cardiac surgery for valve replacement or repair and AF treatment were histologically evaluated for the presence of amyloid deposits. One hundred and four specimens of left and right auricles from 52 patients in sinus rhythm with severe chronic heart failure undergoing heart transplant were also analyzed (controls). Amyloid was found in 33 (46%) valvular patients with chronic persistent AF and in 6 (12%) controls. Amyloid was related to the presence and duration of AF, was more frequently found in left atrial samples and was independent of age. On stepwise logistic regression analysis, AF duration and female gender were independently related to amyloid deposition. Conclusions Patients with long-standing AF and rheumatic heart disease have a very high prevalence of atrial amyloidosis. Amyloid deposition is more frequent in left than in right atrial appendage and correlates with AF duration and female gender. Amyloid deposition could constitute an additional histological feature in the structural remodeling of atria during long-standing AF, at least in rheumatic valve disease. Persistence of AF might play a pivotal role in promoting amyloid deposition.

Background Pulmonary endarterectomy (PEA) is recognized as the best surgical choice for treatment of chronic thromboembolic pulmonary hypertension caused by pulmonary vascular occlusion in eligible patients. This study aims to describe correlations between the daily walk (DW), and the demographic and clinical characteristics of patients undergoing pulmonary endarterectomy. Methods This was a cross-sectional study using data from 32 consecutive patients who had undergone PEA operations and were admitted to the cardiac ward to complete their post-operative rehabilitation. Results Those with a body mass index of ≥25 walked a greater distance during the post-operative rehabilitation phase after PEA compared with those with body mass index Conclusions The authors found that estimation of the DW was a simple, inexpensive, and reliable measure that can help professionals to evaluate patients' post-operative course after PEA.

Pancreatic carcinoma is one of the most lethal cancers in humans. The poor prognosis of this malignancy depends on several factors, such as: lack of early symptoms, advanced stage at detection, early metastatic spread and no effective systemic treatment. To date, only few risk factors for this malignancy are known; therefore, considerable efforts are required to identify additional causative agents involved in the process of pancreatic carcinogenesis. In the last years, a large series of epidemiological investigations have suggested that both bacteria and viruses may play a important role in the initiation and progression of several animal and human cancers. In particular, some studies have showed that hepatitis B (HBV) and hepatitis C (HCV) viruses, two hepatotropic pathogens with well-known oncogenic properties for liver, may be detected also in extra-hepatic tissues, such as pancreas. The aim of this paper is to briefly report the results of available studies, assessing the possible association between HBV/HCV and pancreatic cancer development as well as to discuss the limiting factors of these researches., JOP. Journal of the Pancreas, Vol 14, No 6 (2013): November - p. 603-693

We prospectively investigated whether plasma homocysteine (HCY) concentrations are related to target lesion revascularization (TLR) rates in patients with unstable angina undergoing stenting.We enrolled 196 consecutive patients with at least one successful coronary stent implantation for unstable angina.The mean vessel diameter was 3.1 +/- 0.5 mm. At follow-up (17.8 +/- 7.5 months), patients with higher HCY levels (17 micromol/l, 4th quartile) had similar TLR rates to the rest of the sample (11.1 vs 13.2%, p = 0.90). On the other hand, high HCY levels did seem to be associated with higher total (13.3 vs 0.7%, p = 0.001) and cardiac (6.7 vs 0%, p = 0.01) mortality rates. At multivariate analysis, only target vessel diameter independently predicted TLR, while both HCY levels and target vessel size predicted late total mortality.At least in patients with a mean vessel diameter3 mm, HCY levels cannot be taken as a prognostic indicator of in-stent restenosis for patients with unstable angina. However, in spite of successful percutaneous revascularization, HCY values do seem to strongly influence late mortality.