Clinical and angiographic outcome of a single center,real world population treated with a dedicated technique of implantation for bioresorbable vascular scaffolds. The FAtebenefratelli Bioresorbable Vascular Scaffold (FABS) registry

Objectives

With this prospective study we aim at investigating the long‐term outcome of a consecutive cohort of patients successfully treated with bioresorbable scaffold (BVS) implantation.

Background

It is not clearly understood if there is a relation between the technique of BVS implantation and the outcome.

Methods

Between December 2012 and December 2014, all consecutive patients treated with BVS were included in this registry and received an angiographic follow‐up. After a run‐in phase, all BVS were implanted using a specific technique consisting of aggressive predilation, correct scaffold sizing, visually determined, and high‐pressure post‐dilation with a noncompliance balloon. Primary endpoint was late lumen loss (LLL) at 1‐year angiographic follow‐up and ischemia‐driven target‐lesion revascularization (ID‐TLR) at 2‐year clinical follow‐up. Secondary endpoints were the occurrence of binary restenosis, major adverse cardiac events (MACE), and every single component of MACE (cardiac death, myocardial infarction, TLR) at 2 years.

Results

A total of 144 lesions in 122 patients treated consecutively with BVS, were enrolled. Diabetics were 29.5% and acute coronary syndrome at presentation occurred in 29.5% of patients. At the angiographic follow‐up LLL was 0.38 ± 0.9. At 2‐year clinical follow‐up, ID‐TLR occurred in eight patients (5.6%). We observed two cases of scaffold thrombosis (1.38%, one early and one very late). At multivariate statistical analysis, STEMI presentation remained a significant predictor for TLR.

Conclusions

In a complex, all‐comers real world population, BVS implantation with a specific, and standardized technique showed to be feasible, with acceptable mid‐term angiographic and long‐term clinical outcome.

     

Idiopathic Thrombocytopenic purpura and Helicobacter pylori Infection

Abstract

Objective. As a minimally invasive modality, radiofrequency ablation (RFA) has been increasingly applied not only for the treatment of hepatocellular carcinoma, but also for that of colorectal liver metastasis (CLM). However, RFA for CLM has been shown to be associated with a high local recurrence rate, and no optimal treatment for RFA failure has been established yet. The aim of this study was to evaluate the feasibility and outcome of surgical resection for local recurrence after RFA. Material and methods. A retrospective study of 17 patients, who underwent surgery for local recurrence after RFA for resectable CLM, was carried out. The surgical procedures involved in the actual surgery were compared with those envisioned for the primary resection if RFA had not been selected. Results. Surgical resection for RFA recurrence was more invasive than the envisioned surgical procedure in 10 cases (58%). In addition, the proportions of cases that required technically demanding procedures among the patients receiving surgery for RFA recurrence were higher than those in envisioned operations; major hepatectomy, eight cases [47%] versus two cases [12%] (p < 0.0205); excision and/or reconstruction of the major hepatic veins, three cases [18%] versus zero case [0%] (p = 0.035); excision of diaphragm: three cases [18%] versus zero case [0%] (p = 0.035). The 1-, 3- and 5-year overall survival rates were 92%, 45% and 45%, respectively. Conclusions. Surgical resection for RFA recurrence for CLM required more invasive and technically demanding procedures. Thus, RFA for CLM should be limited to unresectable cases, and patients with resectable CLM should be thoroughly advised not to undergo RFA, but rather surgical resection.     

High prevalence of (99m)tc-tetrofosmin reverse perfusion pattern in patients with myocardial infarction and angiographically smooth coronary arteries

Background: There are no published data in the literature on the scintigraphic perfusion pattern in patients with myocardial infarction (MI) and normal coronary arteries (NCA) Objectives: To evaluate myocardial perfusion imaging in a series of patients with MI and NCA. Methods: Twenty-seven patients who had developed a MI and had NCA were studied. As a control group we included 27 patients with a recent MI and coronary artery disease (CAD). All patients underwent stress/rest tetrofosmin myocardial perfusion SPECT within 6 months from MI. Results: In patients with NCA tetrofosmin stress images revealed 41 hypoperfused segments in 17 patients (63%). On rest images, 13 segments remained unchanged, 4 showed partial reperfusion, 10 normalized and 14 worsened. Additionally, there were 18 new hypoperfused segments in nine patients. Therefore, perfusion worsened at rest in 18 patients (67%) (32 segments). Overall, at rest there were 49 hypoperfused segments in 22 patients (81%). In patients with CAD, stress images revealed 71 hypoperfused segments. On rest images, 39 segments remained unchanged, 16 showed partial reperfusion and 12 normalized. Four segments worsened at rest and only four patients (15%) showed new perfusion defects at rest. Conclusions: Myocardial perfusion with tetrofosmin might appear considerably worse at rest than at stress in patients with MI and NCA. Specifically, a reverse perfusion pattern in the infarct area is a frequent finding and is likely to be due to residual tissue viability. We postulate that in these patients the hyperemic response to exercise may mask resting underperfusion areas.     

The relationship between the severity of hemolysis,clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe

The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study, we assessed the association of hemolysis with outcomes in sickle cell anemia. A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (P≤0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (P≤0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all P<0.0001). Two-year follow-up analysis showed that a high hemolytic component was associated with an increased risk of death (hazard ratio, HR 3.44; 95% confidence interval, CI: 1.2–9.5; P=0.02). The hemolytic component reflects direct markers of intravascular hemolysis in patients with sickle cell disease and allows for adjusted analysis of associations between hemolytic severity and clinical outcomes. These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality (Clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00492531","term_id":"NCT00492531"}}NCT00492531).     

Short-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on functional liver plasma flow in patients with advanced cirrhosis

ABSTRACT— Aims/Background: TIPS, an effective procedure applied for the treatment of complications of portal hypertension, is potentially followed by worsening of the hyperdynamic circulation of cirrhosis and the impairment of liver function. The aim of the present study was to evaluate short-term changes of functional liver plasma flow after application of TIPS, using the hepatic (extrarenal) clearance of D-sorbitol (S-HCl). Methods: Twenty-five cirrhotic patients submitted to TIPS for prevention of variceal rebleeding entered the study. At steady-state, during constant infusion of a solution of D-sorbitol (25 mg/min), appropriate blood and urine samples were collected in order to calculate S-HCl before and 120 min after TIPS opening. In addition, the hepatic extraction ratio of D-sorbitol was directly measured at the level of the right (E_r), where TIPS was applied, and of the left (E_l) hepatic veins; meanwhile the portocaval gradient (PCG) was registered, before and after stent dilation. A comparison of values obtained before and after TIPS application was performed by Student's t-test for paired data. Results: After application of TIPS, a substantial reduction was observed in PCG (12.1 ± 4.2 vs 24.8 ± 4.3 mmHg; p<0.001) and E_r values (20.6 ± 14.8 vs 57.5 ± 22.3%; p<0.001) but not E_l values (47.4 ± 22.0 vs 53.4 ± 21.4%; p=0.178). S-HCl measured 120 min after TIPS opening was not statistically different from pre-TIPS values (389.2 ± 212.1 vs 394.6 ± 152.7 ml/min; p=0.892), although S-HCl variations in Child-Pugh class B patients were positively correlated with portal pressure variations (r=0.63, p=0.016). Conclusion: Our results demonstrate that in patients with advanced cirrhosis, TIPS procedure, while effective in reducing portal hypertension, does not lead to alterations in the functional liver plasma flow within the first 2 h.     

Pattern and management of recurrent hepatocellular carcinoma after liver transplantation

A series of 132 patients who underwent liver transplantation for primary liver cancer was collected from three different Italian hospitals and studied for recurrence of hepatocellular carcinoma after liver replacement. Twenty-one patients (15.9%) had a neoplastic recurrence after an average follow-up period of 7.8 months after transplantation (range, 1—25 months); 15 (71%) occurred within the first 18 months after transplant and only two recurred later than 2 years. The sites of recurrence were grafted liver (19%), lung (19%), bone (14%), and other (5%). Eight patients (38%) had multiple organ involvement at the onset. After 1, 2, 3, and 4 years the overall survival rates were 62%, 43%, 29%, and 23%, respectively. The tumor factors related to early cancer recurrence after transplantation were diameter of nodules more than 3 cm (P < 0.05), tumor stage not meeting the “Milan criteria” (P < 0.03), and presence of peri-tumoral capsule (P < 0.05); the number of nodules, TNM stage, presence of vascular invasion, alpha-fetoprotein level more than 150 UI/l, pre-transplant chemoembolization and resectability of cancer deposits did not seem to be related to early recurrence. The prognosis differed in the 7 patients with resectable recurrences (57% 4-year survival) and the 14 patients with unresectable disease (14% 4-year survival) (P < 0.02). Better patient selection and new combined medical strategies could reduce the incidence of and mortality from liver cancer recurrence after transplantation. The role of surgical resection of recurrence should be further investigated.     

Methylprednisolone Administration in Primary Biliary Cirrhosis Increases Cholic Acid Turnover, Synthesis, and Deoxycholate Concentration in Bile

As immunosuppressive agents, corticosteroids maybe considered an appropriate treatment for primarybiliary cirrhosis, even if bone loss and other sideeffects may occur. We studied biliary lipid metabolism in 10 nonicteric patients, with histologicallyproven primary biliary cirrhosis (stage I-IV). Weadministered methylprednisolone (24 mg daily) for 30days to ascertain its effects on biliary lipidmetabolism, which are largely still unknown. All patientsunderwent a 30-day drug-washout period before enteringthe trial. The following parameters were studied beforeand after methylprednisolone treatment: serum biochemistry; cholic acid pool size, kineticsand synthesis; biliary lipid secretion; biliary bileacid pattern; biliary lipid molar percentage; andcholesterol saturation index. Methylprednisolone induced a statistically significant (Wilcoxon ranktest) increase in cholic acid turnover (from 0.26± 0.04 to 0.50 ± 0.05 K/day, P = 0.005)and synthesis (from 0.42 ± 0.12 to 0.78 ±0.11 mmol/day, P = 0.04), and in bile deoxycholic acid molarpercentage (from 19.4 ± 2.7 to 30.6 ± 4.4%molar, P = 0.01). On the other hand, a significantdecrease in biliary cholesterol molar percentage (from7.9 ± 0.7 to 6.4 ± 0.5 % molar, P =0.005), cholesterol saturation index (from 1.11 ±0.11 to 0.95 ± 0.07, P = 0.05), and biliarycholesterol secretion (from 64.7 ± 5.4 to 53.0± 4.5 mol/hr, P = 0.005) was observed. These findings show thatshort-term administration of methylprednisolone inpatients with primary biliary cirrhosis does not induceexpansion of the cholic acid pool but increases cholicacid synthesis and turnover, as well as intestinalproduction of deoxycholic acid. If long-term treatmentis considered, the beneficial immunosuppressive effectsof corticosteroids have to be weighed against the hepatotoxic properties of deoxycholicacid.     

Different Expression and Function of the Endocannabinoid System in Human Epicardial Adipose Tissue in Relation to Heart Disease

Background

The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease.

Methods

Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N = 18) or valve surgery (nonischemics; N = 15) and in preadipocytes isolated from epicardial adipose tissue.

Results

In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics.

Conclusions

These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target.