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Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain "molar tooth" sign, a finding shared by a group of Joubert syndrome-related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1, is unknown. Methods: We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign. Results: We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity. Interpretation AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD.

Atrial fibrillation is the most common cardiac arrhythmia in adults and increases the risk of stroke 5-fold. In patients with non-valvular atrial fibrillation, left atrial appendage is the most common site for cardiac thrombus. For this reason, left atrial appendage closure (LAAC) represents an effective alternative to oral anticoagulants in patients who have relative or absolute contraindications to oral anticoagulation. Transesophageal echocardiography (TEE) is considered the gold standard imaging modality to guide LAAC. However, general anesthesia and tracheal intubation are often required with the TEE approach, increasing risks in elderly patients. There is an unmet need to overcome these limitations identifying an ideal "minimalist approach" to guide LAAC. Intracardiac echocardiography (ICE) represents a minimalist approach but it suffers from the lack of standardization and it may result in an suboptimal image quality compared with TEE. Another innovative approach is represented by the use of ICE via the transesophageal route (ICE-TEE), which has been already validated to identify the presence of left atrial appendage thrombi and to perform other procedures. In this paper, we suggest that ICE-TEE could be a good alternative imaging technique to guide the LAAC procedure without general anesthesia. A trial is ongoing to demonstrate its safety and effectiveness as ultrasound modality to guide LAAC.

The coronavirus disease 19 (COVID-19) post pandemic evolution is correlated to the development of new variants. Viral genomic and immune response monitoring are fundamental to the surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since 1 January to 31 July 2022, we monitored the SARS-CoV-2 variants trend in Ragusa area sequencing n.600 samples by next generation sequencing (NGS) technology: n.300 were healthcare workers (HCWs) of ASP Ragusa. The evaluation of anti-Nucleocapside (N), receptor-binding domain (RBD), the two subunit of S protein (S1 and S2) IgG levels in 300 exposed vs. 300 unexposed HCWs to SARS-CoV-2 was performed. Differences in immune response and clinical symptoms related to the different variants were investigated. The SARS-CoV-2 variants trend in Ragusa area and in Sicily region were comparable. BA.1 and BA.2 were the most representative variants, whereas the diffusion of BA.3 and BA.4 affected some places of the region. Although no correlation was found between variants and clinical manifestations, anti-N and anti-S2 levels were positively correlated with an increase in the symptoms number. SARS-CoV-2 infection induced a statistically significant enhancement in antibody titers compared to that produced by SARS-CoV-2 vaccine administration. In post-pandemic period, the evaluation of anti-N IgG could be used as an early marker to identify asymptomatic subjects.

Clinical utility of Array-CGH Easychip 8x15K platform can be assessed by testing its ability to detect the occurrence of pathogenic copy number variants (CNVs), and occurrence of variants of uncertain significance (VoUS) in pregnancies without structural fetal malformations. The demand of chromosomal microarray analysis in prenatal diagnosis is progressively increasing in uneventful pregnancies. However, depending on such platform resolution, a genome-wide approach also provides a high risk of detecting VoUS and incidental finding (IF) also defined as "toxic findings." In this context, novel alternative strategies in probe design and data filtering are required to balance the detection of disease causing CNVs and the occurrence of unwanted findings. In a cohort of consecutive pregnancies without ultrasound anomalies, a total of 4106 DNA samples from cultured and uncultured amniotic fluid or chorionic villi were collected and analyzed by a previously designed Array-CGH mixed-resolution custom platform, which is able to detect pathogenic CNVs and structural imbalanced rearrangements limiting the identification of VoUS and IF. Pathogenic CNVs were identified in 88 samples (2.1%), 19 of which (0.5%) were undetectable by standard karyotype. VoUS accounted for 0.6% of cases. Our data confirm that a mixed-resolution and targeted array CGH platform, as Easychip 8x15K, yields a similar detection rate of higher resolution CMA platforms and reduces the occurrence of "toxic findings," hence making it eligible for a first-tier genetic test in pregnancies without ultrasound anomalies.

Background: Syndromic congenital heart disease accounts for 30% of cases and can be determined by genetic, environmental or multifactorial causes. In many cases the etiology remains uncertain. Many known genes are responsible for specific morphopathogenetic mechanisms during the development of the heart whose alteration can determine specific phenotypes of cardiac malformations., Case Presentation: We report on two cases of association of conotruncal heart defect with facial dysmorphisms in sibs. In both cases the malformations' identification occurred by ultrasound in the prenatal period. It was followed by prenatal invasive diagnosis. The genetic analysis revealed no rearrangements in Array-CGH test, while gene panel sequencing identified a new hemizygous variant of uncertain significance (c.887G > A; p.Arg296Gln) in the MED12 gene, located on the X chromosome and inherited from the healthy mother., Conclusion: No other reports about the involvement of MED12 gene in syndromic conotruncal heart defects are actually available from the literature and the international genomic databases. This novel variant is a likely pathogenic variant of uncertain significance and it could broaden the spectrum of genes involved in the development of congenital heart diseases and the phenotypic range of MED12-related disorders.

Chronic organized thrombus as a result of prior untreated myocardial infarction can determine myocardial ischemia. This entity appears as an angiographically irregular and hazy image; optical coherence tomography is useful to evaluate these ambiguous lesions and guide interventional treatment., Competing Interests: None declared., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Objective: The Duchenne/Becker muscular dystrophy (DMD) carrier screening includes the evaluation of mutations in DMD gene, and the most widely used analysis is the multiplex ligation-dependent probe amplification (MLPA) for the DMD deletions/duplications detection. The high frequency of de novo mutations permits to estimate a risk up to 20% of mosaicisms for mothers of sporadic DMD children. The purpose of this study is to evaluate alternative analytical strategy for the detection of mosaics carrier women, in order to improve the recurrence risk estimation., Method: Different DNA and RNA analyses were conducted on samples from a woman that conceived a DMD fetus without previous family history of dystrophynopathy., Results: Standard MLPA analysis failed to identify mosaicism, even if MLPA doses suggested it. Electrophoresis and direct sequencing conducted on RNA permitted to detect two different amplicons of cDNAs, demonstrating the presence of somatic mosaicism. Subsequent detection of a second affected fetus confirmed the mosaic status on the mother., Conclusion: The implementation of RNA analysis in diagnostic algorithm can increase the sensitivity of carrier test for mothers of sporadic affected patients, permitting detection of mosaic status. A revision of analytical guidelines is needed in order to improve the recurrence risk estimation and support prenatal genetic counseling., (© 2018 John Wiley & Sons, Ltd.)

X-linked hydrocephalus (XLH) is a genetic disorder leading to a syndrome characterized by mental retardation, bilateral adducted thumbs, and spasticity of upper and lower limbs. In most cases, X-linked mutation leads to a defective activity of the neuronal cell adhesion molecule L1CAM (L1 cell adhesion molecule, OMIM 308840). Depending on mutations of L1CAM, four X-linked neurological syndromes have been described. These syndromes are very different albeit each one possesses marked variability. In the present study, we describe a novel L1CAM mutation in a 33-year-old woman reporting two voluntary terminations of pregnancy due to fetal hydrocephalus. The genetic analysis identified the potential splicing variant c.1267+5delG. When analyzed in vitro, this mutation produces the skipping of exon 10. The same mutation was confirmed in analyzing DNA from amniocytes from the second pregnancy, and ultrasound scan and autopsy confirmed the occurrence of a severe L1 syndrome. These data describe a novel L1 mutation which improves our understanding on genotype-phenotype correlation while confirming the importance of prenatal screening for L1CAM mutations.

About 10% of causative mutations for mental retardation in male patients involve X chromosome (X-linked mental retardation, XLMR). We describe a case of a 3-year-old boy presenting with developmental delay, autistic features and growth and speech delay. Array-CGH analysis detected a microduplication on the X chromosome (Xp11.2p11.3), spanning 335.4 kb and including 3 known genes (ZNF81, ZNF182 and SPACA5). Genome-wide association studies show that approximately 30% of mutations causing XLMR are located in Xp11.2p11.3, where few pathogenic genes have been identified to date (such as ZNF41, PQB1 and ZNF81). ZNF81 codifies a zinc finger protein and mutations (non-sense mutations, deletions and structural rearrangements) involving this gene have already been described in association with mental retardation. Larger duplications in the same region have also been observed in association with mental retardation, and, in one case, the over-expression of ZNF81 has also been verified by mRNA quantification. No duplications of the single gene have been identified. To our knowledge, the microduplication found in our patient is the smallest ever described in Xp11.2p11.3. This suggests that the over-expression of ZNF81 could have pathological effects., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a recessive X-linked trait, is the most common enzyme deficiency in the world. The most devastating clinical consequence of this deficit is severe neonatal jaundice, which results in sensorineural deficit, and severe haemolytic anemia. However, patients may be asymptomatic. The most common clinical sign is hyperbilirubinemia (h↑), that is also related to Gilbert's syndrome, a condition associated with the promoter polymorphism of the UDP-glucuronosyltransferase 1 (UGT1A1) gene. The aim of this study was to underline (as is usually done by DNA molecular analysis) to detect and to clarify the genetic deficiency that is the reason of the disorder in question. In this study, different techniques were applied to analyse a family of four individuals presenting with hyperbilirubinemia: bilirubinic dosage, electrophoresis and enzymatic activity dosage of G6PD; molecular analysis of the UGT1A promoter to detect a thymine-adenine (TA) insertion, that causes the [A(TA)7TAA] mutation. The results showed that in certain cases, the presence of hyperbilirubinemia is not only associated with G6PD deficiency, but may be caused by the co-presence of a mutation in the UGTA1 promoter related to Gilbert's syndrome. As being affected by these two conditions predisposes to adverse effects towards certain drug treatments, it is advisable to study the UGTA1 gene before prescribing drugs for specific antineoplastic or retroviral treatment. We emphasize that investigating both the UGT1A gene and G6PD activity is the most reliable way to make a correct differential diagnosis.

Background: Although the advancement of the equipment and the presence of innovative techniques, percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) continues to be affected by lower procedural success in comparison with non occluded vessel PCI., Objective: We describe a new technique for the treatment of coronary CTO which utilizes a new generation of polymeric wires., Methods and Result: From March 2009 to June 2010 different strategies were adopted as "bail out" after an initial attempt failed in 117 consecutive CTO lesions. Among these, conventional strategies (CS) such as parallel wire, sub-intimal tracking and re-entry (STAR), microchannel technique, intracoronary ultrasound guided revascularization and anchor balloon, were used in 75 cases (64.1%), while in the remaining a new technique, the "mini-STAR," was used (39.9%). Although no substantial differences were observed regarding the distribution of clinical features and angiographic lesions characteristics between the populations, mini-STAR was able to achieve a higher rate of procedural success in comparison with other CS (97.6% vs. 52%, P < 0.001) with lower contrast agent use (442 ± 259 cm(3) vs. 561 ± 243 cm(3), P = 0.01) and shorter procedural and fluoroscopy times (122 ± 61 vs. 157 ± 74 min, P = 0.009 and 60 ± 31 min vs. 75 ± 38 min, P = 0.03, respectively). No differences were observed in term of peri-procedural complications such as procedural myocardial infarction, coronary perforations, and contrast-induced nephropathy between mini-STAR and CS., Conclusion: The mini-STAR technique is a promising strategy for the treatment of CTO lesions, achieving a high procedural success rate and low occurrence of procedural adverse events., (Copyright © 2011 Wiley Periodicals, Inc.)

Interstitial deletion of the short arm of chromosome 4, excluding cytoband p16, has been described as a distinct phenotype from the Wolf-Hirschhorn syndrome, characterized by a deletion encompassing cytoband p16. We report on the case of a 14-month-old boy with an apparently isolated craniosynostosis and harboring a de novo microdeletion in band 4p15. The imbalance, about 4 Mb in size is, to date, the smallest deletion ever described in this region, encompassing 12 genes. A comparison with other previously described cases of 4p15 deletion is made, and the possible roles of some genes involved in the deletion are discussed., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Drug-eluting stents showed a better angiographic and clinical outcome in comparison with bare metal stent in chronic total occlusions (CTOs) percutaneous revascularization, however, great concerns still remain regarding the rate of restenosis and reocclusion in comparison with nonocclusive lesions., Aim: To evaluate angiographic and clinical outcomes after sirolimus-eluting stent (SES) implantation in the setting of a "real world" series of complex CTOs., Methods and Results: From January 2006 to December 2008, 172 consecutive patients with 179 CTO lesions were enrolled into registry. Among these, successful recanalization was obtained in 144 lesions (80.4%) with exclusive SES implantation in 104 lesions. The 9-12 months angiographic follow-up was executed in 85.5% of lesions with evidence of angiographic binary restenosis in 16.8% of lesions. Total stent length and number of stent implanted were recognized as independent predictors of restenosis (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.28-107.09, P = 0.02) and (OR 5.8, 95% CI 1.39-23.55, P = 0.01), respectively.The 2-year clinical follow-up showed rates of target lesion revascularization, non-Q wave myocardial infarction, and total major adverse cardiovascular events (MACEs) of 11.1%, 2%, and 13.1%, respectively. Cox proportional-hazard analysis showed diabetes as independent predictor of MACEs (hazard ratio [HR] 4.832; 95% CI, 0.730-0.861; P = 0.028)., Conclusions: Data from this registry demonstrate the long-term efficacy and safety of SES implantation after complex CTOs recanalization., (©2011, Wiley Periodicals, Inc.)

Aims: In comparison with non-occlusive lesions, percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) represents a greater challenge for the interventionalist, due to lower procedural success rates, relatively higher incidence of procedural complications and the increased rate of restenosis. The European Registry of Chronic Total Occlusion (ERCTO) was created with the goal of evaluating the real impact of CTO PCI in the European context, trying to analyse the rates of procedural success, technical information from the CTO procedures and patient outcome., Methods and Results: Data collection was carried out in 16 centres across Europe, starting from the beginning of January 2008. In two years of activity, a total of 1,914 patients with 1,983 CTO lesions were consecutively enrolled in the registry. Overall procedural success was achieved in 1,607 lesions (82.9%); anterograde procedures obtained higher procedural success of retrograde ones (83.2% versus 64.5%, p<0.001). Coronary perforation occurred more frequently in patients who underwent retrograde approach (4.7% versus 2.1%, p=0.04). Although no differences were observed in terms of 30-day major adverse cardiac events between anterograde and retrograde treated patients, a trend toward higher periprocedural non-Q-wave myocardial infarction was found in patients in which the retrograde approach was attempted (2.1% versus 1% p=0.08). Moreover, retrograde approach was related with longer procedural and fluoroscopy times (156.9±62.5 min vs. 98.2±52.8 min and 73.3±59.9 min vs. 38.2±43.9 min respectively, p<0.001) and higher contrast load administration (402±161 cc vs. 302±184 cc, p<0.001)., Conclusions: The first report of the ERCTO registry by the EuroCTO club shows a high procedural success rate obtained by expert European operators in a "real-world" consecutive series of patients, comparable with those reported by Japanese registries. The rate of observed procedural adverse events was low and similar to the non-CTO PCI series. In this registry, retrograde procedures were associated with extended fluoroscopy exposure and procedural time, increased contrast load administration as well as a higher incidence of coronary perforations. Such outcomes should become the standard of care that all centres undertaking CTO PCI should aspire to.

Objectives: The aim of this study is to verify the study hypothesis of the EXCEL trial by comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in an EXCEL-like population of patients., Background: The upcoming EXCEL trial will test the hypothesis that left main patients with SYNTAX score ≤ 32 experience similar rates of 3-year death, myocardial infarction (MI), or cerebrovascular accidents (CVA) following revascularization by PCI or CABG., Methods: We compared the 3-year rates of death/MI/CVA and death/MI/CVA/target vessel revascularization (MACCE) in 556 patients with left main disease and SYNTAX score ≤ 32 undergoing PCI (n = 285) or CABG (n = 271). To account for confounders, outcome parameters underwent extensive statistical adjustment., Results: The unadjusted incidence of death/MI/CVA was similar between PCI and CABG (12.7% vs. 8.4%, P = 0.892), while MACCE were higher in the PCI group compared to the CABG group (27.0% vs. 11.8%, P < 0.001). After propensity score matching, PCI was not associated with a significant increase in the rate of death/MI/CVA (11.8% vs. 10.7%, P = 0.948), while MACCE were more frequently noted among patients treated with PCI (28.8% vs. 14.1%, P = 0.002). Adjustment by means of SYNTAX score and EUROSCORE, covariates with and without propensity score, and propensity score alone did not change significantly these findings., Conclusions: In an EXCEL-like cohort of patients with left main disease, there seems to be a clinical equipoise between PCI and CABG in terms of death/MI/CVA. However, even in patients with SYNTAX score ≤ 32, CABG is superior to PCI when target vessel revascularization is included in the combined endpoint., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Previous studies have reported that the indeterminable aging and long-duration occlusion are associated with procedural failure and adverse long-term outcome. We aimed to investigate the clinical impact of occlusion duration in a consecutive series of patients who underwent percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions., Methods and Results: From October 2005 to June 2009, a total of 303 patients with 328 CTO lesions were consecutively treated achieving a success rate of 86.3%. The average of occlusion duration estimated in 62.5% of cases (known occlusion duration [KOD] patients, n = 188) was 29.8 ± 41.3 months. In the remaining 37.5% of cases, the occlusion duration was indeterminate (indetermination of occlusion duration [IOD] patients, n = 115). No influence of duration in procedural outcome was observed. Moreover, no differences of 1-year major adverse cardiac events (MACE) were observed between KOD and IOD patients. The multivariate COX regression analysis identified diabetes mellitus and multivessel coronary disease as independent predictors of 12-month MACE (HR 5.023; 95% CI 0.164-9.653; P = 0.025 and HR 0.801; 95% CI 0.109-0.909, P = 0.033). The analysis did not show any influence of IOD and long occlusion duration in the occurrence of MACE. Predictors of angiographic failure recognized with multivariate binary logistic were vessel diameter <2.5 mm (OR 5.3; 95% CI 1.19-8.91; P = 0.02), CTO length >20 mm (OR 6.3; 95% CI 1.22-9.54; P = 0.02), and severe calcification (OR 3.2; 95% CI 1.62-5.51; P = 0.03)., Conclusion: IOD and long duration of CTO do not affect procedural and clinical outcome of patients who underwent CTO PCI. This marks the importance of considering PCI treatment, a reliable strategy in cases of IOD or long occlusion duration., (©2011, Wiley Periodicals, Inc.)

Objectives: Strut coverage represents the most powerful morphometric predictor of stent thrombosis and the best surrogate indicator of endothelization. The aim of this study was to get new insights on temporal patterns of vessel healing after stenting with different types of stent., Methods: Optical coherence tomography (OCT) was used to investigate the early strut coverage of lesions treated with CATANIA (CAT) stent, drug-eluting stent (DES) or cobalt-chromium bare metal stent (BMS). Two cohorts of 10 and 24 patients underwent OCT follow-up at 7-10 and 28-32 days after stenting, respectively. In each cohort, patients were randomly assigned to receive a CAT stent in one lesion and a BMS or a DES in a separate lesion., Results: A total of 7975 and 8406 struts were analyzed for the comparisons of CAT stent vs. DES and CAT stent vs. BMS at 7-10 days, respectively. A total of 21 123 and 25 069 struts were analyzed for the comparisons of CAT stent vs. DES and CAT stent vs. BMS at 28-32 days, respectively. At 7-10 days, the CAT stent showed higher coverage rates compared with DES (90.0 vs. 85.9%, P < 0.0001) and BMS (90.2 vs. 83.6%, P < 0.0001). Similarly, at 28-32 days, the coverage rate was higher with CAT stent compared with DES (97.7 vs. 90.5%, P < 0.0001) and BMS (97.2 vs. 96.5%, P < 0.0001)., Conclusion: The CAT stent yields quicker and more complete strut coverage than DES and BMS in the early phases of vessel healing following stent implantation.

Several studies have produced estimates of the outcome of percutaneous coronary intervention (PCI) in the field of left main (LM) coronary artery disease, but no research has been found that surveyed the issue of a comprehensive knowledge of LM anatomy and assessed the impact of different anatomic phenotypes on the likelihood of developing complications after LM PCI. We sought to develop a specific investigation on the basis of the regional anatomy and quantitative analysis of a large series of angiograms performed in our institution. We reviewed the baseline selective digital coronary angiographic examinations of 1,000 patients who did not undergo LM PCI and 296 patients with significant LM stenosis who did undergo PCI. All patients in both groups underwent a comprehensive qualitative and quantitative assessment of LM anatomical features according to several parameters. Hierarchical cluster analysis (HCA) was used to identify different anatomic phenotypes of the LM coronary artery. Three different anatomical patterns were identified by HCA. The proportion of patients with LM disease increased across clusters (19% in cluster 1, 27% in cluster 2 and 44% in cluster 3, p < 0.001). No differences were observed in terms of 18-month major adverse cardiac event-free survival among patients with LM disease undergoing PCI stratified by clusters (log rank p = 0.77). In conclusion, LM phenotypes can be identified that are more likely to present with atherosclerotic disease and significant stenosis.

Objectives: The aim of this study was to investigate the association between plaque distribution at left main (LM) bifurcation and target lesion revascularization (TLR) after stenting., Background: Despite favorable reported mid- and long-term results, stent implantation on LM bifurcation remains challenging. The role of atherosclerotic plaque distribution in affecting LM bifurcation stenting outcomes has not been explored., Methods: A total of 329 patients undergoing LM bifurcation stenting in 2 centers were included. A method based on different plaque locations within the bifurcation area was applied. The overall population was divided in 2 groups according to the presence of a specific pattern characterized by plaque occupying (n = 145) or not occupying (n = 184) the whole bifurcation (WB) area., Results: Baseline clinical, angiographic, and procedural characteristics were well-balanced between the 2 groups. The WB group showed a significantly higher risk of 3-year TLR compared with the non-WB group (24.9% vs. 8.3%; unadjusted hazard ratio: 3.12; 95% confidence interval: 1.59 to 6.11; p = 0.001; adjusted hazard ratio: 2.84; 95% confidence interval: 1.43 to 5.64; p = 0.003). The 3-year TLR rate was not significantly different between patients treated with 1-or 2-stent techniques either in the WB or non-WB groups. In the WB group, TLR was similar between patients with lesions classified as 1,1,1 and non-1,1,1 by the Medina classification (20.7% vs. 26.8%, p = 0.57, respectively)., Conclusions: The WB pattern is associated with enhanced TLR risk, regardless of stent technique and plaque severity. This could impact the treatment strategy of high-risk lesions involving the whole bifurcation area., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prognostic value of exercise myocardial scintigraphy in patients undergoing incomplete revascularization by means of percutaneous coronary intervention (PCI) with at least a residual chronic total occlusion (CTO) left untreated., Methods: Of 569 consecutive patients with multivessel disease undergoing myocardial scintigraphy after incomplete revascularization by PCI between March 1997 and December 2004, 126 (79% male, 64+/-10 years) with >or= 1 residual CTO fulfilled the eligibility criteria and entered in the study. Hard events defined as cardiac death and myocardial infarction, soft events defined as incidence of unstable angina and PCI procedures, and their composite were assessed at a median follow-up period of 44 months., Results: Hard events were observed in six patients (4.8%). All of them had severely abnormal perfusion defects detected by myocardial scintigraphy. Soft events occurred in 0 (0%), 10 (7.9%), and 15 (11.9%) patients with normal, mildly abnormal, and severely abnormal perfusion, respectively. In the Kaplan-Meier analysis, the log-rank test was statistically significant across patients stratified by summed stress score either in terms of hard, soft and hard, or soft events. Univariate and multivariate Cox proportional-hazards showed an incremental significant information when the scintigraphic variables were added to clinical, angiographic, left ventricular ejection fraction, and Duke treadmill score, for prediction of the composite of hard and soft cardiac events (P < 0.006)., Conclusions: Among patients with a residual CTO left untreated after PCI, myocardial perfusion imaging provides significant independent information concerning the subsequent risk of cardiac events.

We studied the clinical, neuropsychological, neurophysiologic, and genetic features of an Italian family with familial cortical myoclonic tremor with epilepsy (FCMTE). Clinically affected members of the family had limb and voice tremor, seizures, and myoclonus involving the eyelids during blinking. Neuropsychological testing disclosed visuospatial impairment, possibly due to temporal lobe dysfunction. Neurophysiologic findings suggested increased primary motor cortex excitability with normal sensorimotor integration. Linkage analysis excluded the 8q24 locus, where patients shared a common haplotype spanning 14.5 Mb in the pericentromeric region of chromosome 2.

Objectives: This retrospective study sought to assess the clinical and angiographic long-term outcome after implanting drug-eluting stents in bifurcation lesions with the T-provisional (T-prov) technique and mini-crush (MC) technique., Background: The best option on the treatment of coronary bifurcation lesions is a subject of considerable debate. However, recent evidence suggests that bifurcation lesions might be treated by drug-eluting stent on both branches using the MC technique with a low rate of major adverse cardiac event and restenosis., Methods: From April 2004 to July 2006, 457 patients were consecutively treated with either MC technique (n = 199) or T-prov technique (n = 258). Of these latter, 170 patients were treated with 1 stent and 88 patients with 2 stents. The 9-month angiographic follow-up was completed in 188 of 229 (82.1%) bifurcation lesions of MC patients and in 207 of 266 lesions (77.8%) of T-prov patients., Results: After a propensity score adjustment, 2-year cumulative major adverse cardiac events were similar between groups (p = 0.16). The MC group compared with the T-prov 1-stent group had significantly lower main and side branches restenosis (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.27 to 0.99; p = 0.047; and HR: 0.41, 95% CI: 0.20 to 0.85; p = 0.016, respectively). However, the MC group compared with the T-prov-only group had significantly lower side branch restenosis (HR: 0.55, 95% CI: 0.37 to 0.82; p = 0.004)., Conclusions: Both techniques of bifurcation treatment met high procedural success with low complication rates and similar major adverse cardiac event long-term outcome. However, the MC technique yields a lower restenosis rate at both main and side branches. These results may confirm the advantage of using prescheduled 2-stent technique to give a complete coverage of the side branches' ostium.

Aim: Stenosis in the unprotected left main coronary artery (ULMCA) is considered a standard indication for surgical revascularization. Some studies have demonstrated that stenting of the ULMCA is safe and feasible in selected patients. Drug eluting stents (DES) have been shown to be superior to bare metal stents (BMS) in reducing restenosis and major adverse cardiac events (MACE) both in-hospital and at follow-up after treatment of ULMCA disease. Several studies showed that the mid-term prognosis of patients with left main stenting is good, but most of them are limited by small populations and the availability of mid-term results. Thus, we sought to evaluate the very long term impact of DES vs BMS in a large cohort of patients undergoing stent implantation for ULMCA disease in our center., Methods: Between June 2002 and June 2008 a total of 354 consecutive patients with ULMCA stenosis were treated with percutaneous coronary intervention with BMS (53 patients) or DES (301 patients) implantation. A multivariable adjustment was provided in order to account for baseline differences between groups., Results: The average clinical follow-up was 551+/-512 days. Overall, MACE rate was significantly lower in the DES group (16.6% vs 26.4%, P=0.02). The beneficial effect was driven by a reduction of death (6.0% vs 9.4%, P=0.11), MI (2.7% vs 3.8%, P=0.33) and target vessel revascularization after DES implantation (9.0 % vs 15.1%, P=0.11). After correcting for independent predictors of adverse events, the adjusted hazard ratios (HRs) for the risk of mortality and myocardial infarction after DES implantation relative to BMS implantation were 0.99 (95% CIs 0.30-3.21, P=0.98) and 0.59 (95% CIs 0.01-3.45, P=0.56), respectively. The adjusted HR for two-year MACE was 0.50 (95 CIs 0.25-1.02), P=0.056, mainly driven by a statistical significant reduction of TVR (HR 0.30 [95 CIs 0.11-0.82], P=0.018]., Conclusions: Patients presenting with ULMCA disease, who are treated with DES have a significant reduction in the rate of target lesion revascularization with no increased risk of death or myocardial infarction.