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Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 or NPC2 genes. In 2009, the molecular characterization of 44 NPC Italian patients has been published. Here, we present an update of the genetic findings in 105 Italian NPC patients belonging to 83 unrelated families (77 NPC1 and 6 NPC2). NPC1 and NPC2 genes were studied following an algorithm recently published. Eighty-four different NPC1 and five NPC2 alleles were identified. Only two NPC1 alleles remained non detected. Sixty-two percent of NPC1 alleles were due to missense variants. The most frequent NPC1 mutation was the p.F284Lfs*26 (5.8% of the alleles). All NPC2 mutations were found in the homozygous state, and all but one was severe. Among newly diagnosed patients, 18 novel NPC1 mutations were identified. The pathogenic nature of 7/9 missense alleles and 3/4 intronic variants was confirmed by filipin staining and NPC1 protein analysis or mRNA expression in patient’s fibroblasts. Taken together, our previous published data and new results provide an overall picture of the molecular characteristics of NPC patients diagnosed so far in Italy.

Large thrombus burden (LTB) lesions in the context of primary percutaneous coronary intervention (p-PCI) have been related to unsuccessful angiographic reperfusion and unfavorable clinical outcomes. However, the hazard of LTB treatment on myocardial damage has not been evaluated. We investigated the impact of LTB on myocardial damage using contrast-enhanced cardiac magnetic resonance (CE-CMR) in the setting of p-PCI. In 327 patients, who underwent p-PCI without thrombus aspiration within 12 hours from symptom onset, we prospectively assessed the impact of LTB on infarct size and microvascular damage using CE-CMR. LTB was defined by the presence of Thrombolysis In Myocardial Infarction thrombus score ≥3 in patent infarct-related artery (IRA); or by "cut-off" occlusion pattern and/or large reference vessel diameter (≥3.5 mm) in occluded IRA. One hundred ninety-seven patients (60.2%) showed LTB and 130 (39.8%) did not. Distal embolization occurred in 18.8% patients with versus 6.9% without LTB (p = 0.003). At CE-CMR, patients with LTB had larger infarct size index (27.5 ± 11.1 vs 22.1 ± 17.5, p = 0.009) and more often transmural necrosis (70.5% vs 55.4%, p = 0.008) compared with patients without LTB. Excluding patients with distal embolization, patients with LTB still had larger necrosis. At multivariate analysis, occluded (IRA) at baseline, anterior infarction, and presence of LTB predicted transmural necrosis. In conclusion, LTB in the setting of p-PCI is related to larger myocardial damage as detected by CE-CMR, regardless of angiographic detectable distal embolization.

This study aims to develop and validate a new angiographic risk score to predict the risk of distal embolization (DE) during primary percutaneous coronary intervention (p-PCI) for ST-elevation myocardial infarction. Study included data from 1,200 patients who underwent p-PCI. The cohort was randomly split into a derivation cohort (n = 814) and a validation cohort (n = 386). Logistic regression was used to examine the relation between risk factors and the occurrence of DE. To each covariate in the model was assigned an integer score based on the regression coefficients. Variables included in the risk score, according to multivariable analysis, were occlusion pattern of infarct-related artery, Thrombolysis In Myocardial Infarction Thrombus Score 2 to 4, reference vessel diameter ≥3.5 mm, and lesion length >20 mm. To each variable was assigned a 0- to +2-point score according to the strength of the statistical association. Rates of DE in low-, intermediate-, and high-risk groups were 5.6%, 15.8%, and 40% in the derivation cohort (p for trend

BackgroundRecent studies have described neo-atherosclerosis, developing inside the stent, as cause of very late stent thrombosis.Case reportA 59-year-old man, with family history of coronary artery disease, presented to our Department because of anterior ST-segment elevation myocardial infarction. Two years before he had underwent percutaneous coronary intervention with multiple drug-eluting stents (DES) implantation on proximal-mid left anterior descending artery (LAD), and mid-right coronary artery (RCA), respectively. The angiogram revealed stent thrombosis with total occlusion of proximal LAD. Multiple passages with manual thrombus-aspiration catheter were successfully performed with improvement in TIMI flow. Optical Coherence Tomography (OCT) imaging revealed fully expanded stents without areas of inappropriate apposition to vessel wall; and mild to moderate intimal hyperplasia throughout the stented segment, with full covered stent struts; areas of ulcerated and ruptured plaque within the proximal struts of stented segment was depicted with intraluminal protruding material. Thus, an additional bare metal stent (BMS) was deployed inside and overlapping the previous in order to seal this plaque. OCT post procedure revealed optimal stent expansion and apposition, without residual protruding material. At 9-month follow-up patient was alive and free from symptoms. Coronary angiogram revealed patency of implanted stents without significant restenosis.ConclusionsNeo-atherosclerosis with thrombosis on top of ruptured necrotic plaque core may play a role in the pathophysiology of very late stent thrombosis in both BMS and DES. Our report highlights the role OCT to assess the mechanism of VLST.

RhGM/CSF (Sehering Plough, Milan) was administered to two patients (7 yrs and 12 yrs respectively) with GSD lb with histories of frequent bacterial infections, and perineal abscesses. These episodes occurred despite continues prophylactic treatment with trimethoprim-sulfamethoxyazole. During two year treatment only patient C.P. had 2 slight episodes of stomatitis, following virus-induced bronchitis. Both patients had no clinical side effects, except for pomphoyd hyperemic areas around the injection sites at the 3th week of therapy all through 3 days. Laboratory investigations. Absolute neutrophyl counts (ANC) in patient C.P. ranged from 100 to 650 mm3. Bone marrow aspirates showed maturation delay of white cells series. He began treatment with GM CSF, 5 ug/Kg/day and the ANC increased to 4200 mm3 in I day and 9150 mm3 in 10 days. Over the past two year the dose was lowered to 3 ug/kg/day. This median ANC has been 2670 mm3 (range 1200-4800) and H2O2 production and granulocyte chemotaxis improved (from 77 to 138). In patient A.A. treatment with GM-CSF (6 ug/kg/day) induced a rapid increase in ANC from less than 370 to 1960 mm3 within 2 days. At dose of 5 ug/kg/day his median ANC has been 2600 mm3 (range 1200-3150); H2O2 production and granulocyte chemotaxis were never modified. After two years therapy we assume that GM-CSF is effective and indicate in patients with GSD lb. The high cost of GM-CSF and the rapid decreased of ANC after discontinuation of the therapy (1 day) has to be anyway evaluated.

BackgroundCoronary stent fracture is an under-recognized event but one that has been reported frequently in the drug-eluting stent era. Most reported cases of stent fracture occurred within days to two years after implantation, and are related to stent thrombosis and restenosis.Case reportPresentation of a 69-year-old male with a history of arterial hypertension and previous percutaneous coronary intervention (PCI), and with implantation of three overlapping drug-eluting stents (DES) on proximal-to-middle left anterior descending artery (LAD). At five-year outpatient evaluation, the patient was found to have a new left bundle branch block associated with mild elevation in Troponin-I value and severe left ventricular dysfunction. The patient recovered as non ST-segment elevation myocardial infarction (NSTEMI) and consequently a new coronary angiography showed total occlusion of proximal LAD with multiple stent fracture. Here we discuss the role of left ventricular dilatation as a contributing factor to late drug-eluting stent fracture.ConclusionDifferent anatomical coronary settings have been described as predisposing factors to stent fracture. Consequently, the remodeling of the left ventricle, together with the rise in diastolic pressure, may have affected the shear stress of LAD stents by increasing mechanical forces produced in the diastolic phase on the epicardial vessel. In addition, left ventricular enlargement could have increased the elongation forces on the stent frames by altering the curvature of the stent. All predisposing factors of stent fracture, including coronary and left ventricular issues, need to be considered before stent implantation to avoid stent fracture and clinical sequelae.

performed a study to assess long-term survival in OHCA patients managed with CA on admission and PCI if indicated and to compare survival between patients with and without acute myocardial infarction (AMI). Methods: Retrospective single-centre study including patients 18 y.o. resuscitated from an OHCA without an obvious non-cardiac cause. AMI was diagnosed angiographically as lesions suggestive of ruptured plaques with fresh thrombus and critical stenosis easily crossed by an angioplasty wire. Survival was recorded at discharge and 5-years survival probability was estimated by Kaplan-Meier survival curves. Data are expressed as numbers (percentages) and median (interquartile range-IQR). Results: 300 comatose patients aged 56 (48-67) were included from 2002 to 2011. 130 patients (43%) had ventricular fibrillation, 116 (39%) asystole, 54 (18%) had other/unknown initial rhythm. All patients had CA on admission and 93 (31%) had an AMI. PCI was attempted in 85 (91%) of AMI patients, successful in 79. Therapeutic hypothermia was performed in 256 (84%) patients. Survival at discharge was 32.3% (97/300). After discharge, 5-year probability of survival was 81.7 5.4%. Probability of survival from admission to 5 years was 26.2% 2.8%. AMI patients had better survival at discharge, 40.8% (38/93) versus 28.5% (59/207) in non-AMI, p1⁄40.047. Probability of survival from discharge to 5 years in AMI patients was 92.2% 5.4% versus 73.4 8.6% in non-AMI, hazard ratio (HR)1⁄42.7, confidence interval (CI)1⁄4(0.8-8.9), p1⁄40.1. Survival probability from admission to 5 years was better for AMI patients, 37.4% 5.2% versus, 20.7% 3.0% in non-AMI, HR1⁄41.5, CI1⁄4(1.122.0), p1⁄40.0067. Conclusions: We observed a very favourable post-discharge prognosis in OHCA patients undergoing on-admission CA with PCI if indicated. Patients suffering OHCA due to AMI had better survival to discharge and at 5 years follow-up than patients suffering OHCA due to other causes.