Functional imaging through scattering medium via fluorescence speckle demixing and localization.

Recently, fluorescence-based optical techniques have emerged as a powerful tool to probe information in the mammalian brain. However, tissue heterogeneities prevent clear imaging of deep neuron bodies due to light scattering. While several up-to-date approaches based on ballistic light allow to retrieve information at shallow depths inside the brain, non-invasive localization and functional imaging at depth still remains a challenge. It was recently shown that functional signals from time-varying fluorescent emitters located behind scattering samples could be retrieved by using a matrix factorization algorithm. Here we show that the seemingly information-less, low-contrast fluorescent speckle patterns recovered by the algorithm can be used to locate each individual emitter, even in the presence of background fluorescence. We test our approach by imaging the temporal activity of large groups of fluorescent sources behind different scattering phantoms mimicking biological tissues, and through a brain slice with a thickness of ∼200 µm.

The physiological sonographic features of the ovary in healthy subjects: a joint systematic review and meta-analysis by the Italian Society of Gynecology and Obstetrics (SIGO) and the Italian Society of Endocrinology (SIE).

PURPOSE: There is a lack of uniformity in the definition of normal ovary ultrasound parameters. Our aim was to summarize and meta-analyze the evidence on the topic. Full-text English articles published through December 31, 2020 were retrieved via MEDLINE and Embase. Data available for meta-analysis included: ovarian follicular count, ovarian volume, and ovarian Pulsatility Index (PI) assessed by Doppler ultrasound. METHODS: Cohort, cross-sectional, prospective studies with a single or double arm were considered eligible. Interventional studies were included when providing baseline data. Both studies on pre- and post-menopausal women were screened; however, data on menopausal women were not sufficient to perform a meta-analysis. Studies on pre-pubertal girls were considered separately. Eighty-one papers were included in the meta-analysis. RESULTS: The mean ovarian volume was 6.11 [5.81-6.42] ml in healthy women in reproductive age (5.81-6.42) and 1.67 ml [1.02-2.32] in pre-pubertal girls. In reproductive age, the mean follicular count was 8.04 [7.26-8.82] when calculated in the whole ovary and 5.88 [5.20-6.56] in an ovarian section, and the mean ovarian PI was 1.86 [1.35-2.37]. Age and the frequency of the transducers partly modulated these values. In particular, the 25-30-year group showed the higher mean follicular count (9.27 [7.71-10.82]), followed by a progressive age-related reduction (5.67 [2.23-9.12] in fertile women > 35 years). A significant difference in follicular count was also found according to the transducer's upper MHz limit. CONCLUSION: Our findings provide a significant input to improve the interpretation and diagnostic accuracy of ovarian ultrasound parameters in different physiological and pathological settings.

Wrist circumference is a biomarker of adipose tissue dysfunction and cardiovascular risk in children with obesity.

PURPOSE: To evaluate the relationship between wrist circumference, markers of adipose dysfunction, and cardiovascular risk in youths with obesity. METHODS: In this cross-sectional study, we measured body mass composition by dual-energy X-ray absorptiometry, wrist circumference, waist-to-height ratio, fasting blood insulin, glucose, lipid profile, adiponectin, and leptin in 280 children with overweight/obesity and without diabetes (age: 7-18 years). Cardiovascular risk was estimated by "metabolic syndrome score" (MetS score). RESULTS: Study participants had median [25th-75th percentile] wrist circumference of 17.5 [16.7-18.5] cm and waist-to-height ratio of 0.62 [0.59-0.67]. Lower adiponectin-leptin ratio was found among subjects in the upper 50th percentiles of wrist circumference [0.17 (0.09-0.36) vs. 0.38 (0.16-0.79); p < 0.001]. Wrist circumference was independently associated with MetS score (r = 0.5 p < 0.001). Among MetS score components, an independent association between wrist circumference HDLc, triglycerides, and systolic blood pressure was found (r = - 0.253 p < 0.001; r =+ 0.204 p < 0.001; r = + 0.403 p = < 0.001, respectively). The coefficient of determination for MetS score was nominally higher when considering wrist circumference as independent variable (Adj-R2 = 0.30) then when considering body mass index SD (Adj-R2 = 0.28), waist-to-height ratio (Adj-R2 = 0.26) or truncal fat percentage (Adj-R2 = 0.01). The addition of wrist circumference in age and gender adjusted models, accounting to any other anthropometric parameters, resulted in a significant improvement of the Adj-R2 (p < 0.001 for all). CONCLUSIONS: Our study shows that wrist circumference independently relates to adiponectin-leptin ratio and to the prediction of cardiovascular risk, suggesting it as an efficient and adjunctive anthropometric marker of cardiometabolic risk in children with obesity.

Weaning of infants from non invasive ventilation.

Non invasive ventilation (NIV) is commonly used to treat RDS in preterm infants. Although less risky than invasive ventilation, NIV has some potential side effects and appropriate weaning is therefore desirable. However, criteria for the definition of stability prior to attempting NIV weaning as well as the best weaning strategies need to be more investigated. The aim of this review is to identify criteria and interventions that can facilitate correct weaning from NIV.

The dual Aurora kinase inhibitor ZM447439 prevents anaplastic thyroid cancer cell growth and tumorigenicity.

The anaplastic thyroid cancer (ATC) is among the most aggressive human tumors which fail to respond to all the currently available therapeutic approaches. As a consequence most patients die within a few months from diagnosis. In the present preclinical study, the effects of the ZM447439, a functional inhibitor of Aurora kinases, on the growth and tumorigenicity of a panel of ATC derived cell lines (CAL-62, 8305C, 8505C and BHT-101) were evaluated. The treatment of the different ATC cells with ZM447439 inhibited proliferation in a time- and dose-dependent manner, with IC50 comprised between 0.5 mM and 5 mM. Moreover, the drug remarkably impaired the formation of colonies in soft agar of all the cell lines. Consistently with Aurora inhibition, immunofluorescence and immunoblotting experiments demonstrated that Aurora auto-phosphorylation following drug treatment was completely abrogated, and treated cells were characterized by the presence of multiple spindles with short microtubules. In the same experiments we observed the loss of histone H3 phosphorylation on Ser10, specifically due to Aurora-B, after ZM447439 treatment. Time-lapse videomicroscopy and flow cytometric analysis demonstrated that in presence of ZM447439 the cells were able to enter mitosis but not to complete it, becoming polyploid. Almost all the ATC cell lines studied showed increased apoptosis after only 48 h of treatment. In conclusion, our data demonstrate that ZM447439 is effective in reducing cell growth and tumorigenicity of different ATC derived cell lines, and further investigations are needed to exploit its potential therapeutic value for ATC treatment.

Incidence and very long- term outcomes of stent thrombosis after bare-metal or drug-eluting stent implantation: a retrospective analysis.

AIM: Stent thrombosis is a major safety issue after percutaneous coronary intervention (PCI) with stent implantation and it is associated with major early and mid-term complications. However, its long-term impact has been incompletely described. We thus aimed to appraise incidence, predictors and very long-term outlook of stent thrombosis after bare metal stent (BMS) or drug-eluting stent (DES) implantation. METHODS: We identified all patients undergoing PCI with BMS or DES at our center between July 2002 and June 2004. For the purpose of this study, we employed a composite definition of stent thrombosis including any Academic Research Consortium stent thromboses (definite, probable, or possible). We adjudicated the following clinical events: death, myocardial infarction (stent thrombosis related), repeated revascularization, and the composite of these events (i.e., major adverse cardiac events, MACE). RESULTS: A total of 1112 patients were included, 854 (76.8%) treated with BMS and 258 (23.2%) treated with DES. At a median follow-up of 61.2 (11.03) months the incidence of stent thrombosis was 20 (1.8%), with 14 (1.3%) definite, 4 (0.4%) probable, and 2 (0.1%) possible according to the American Research Consortium statement. Patients developing stent thrombosis were more likely to have more complex angiographic features at baseline (including angiographically evident thrombus, 4 [20%] vs. 73 [6.6%], P=0.02) and a saphenous vein graft as target vessel (2 [10%] vs. 28 [2.5%], P=0.04). Conversely, being treated with a BMS or a DES did not confer any significant decrease or increase in the risk of stent thrombosis, as 7 [35%] of those with stent thrombosis had received at least a DES vs. 251 [22.9%] of those without stent thrombosis, P=0.28). Early clinical outcomes (at 30 days) distinguishing those with stent thrombosis versus those without were as follows: death in four (20%) vs. 2 (0.2%, P<0.001), myocardial infarction in 1 (5%) vs. 7 (0.6%, P=0.02), revascularization in 5 (25%) vs. 43 (3.9%, P<0.001), and MACE in 8 (40%) vs. 53 (4.8%, P<0.001). After more than 60 months of clinical follow-up, outcomes were as follows: death in 7 (35%) vs. 147 (13.5%, P=0.057), myocardial infarction in 6 (30%) vs. 40 (3.6%, P<0.001), revascularization in 15 (75%) vs. 317 (29%, P<0.001), and MACE in 19 (95%) vs. 453 (41.5%, P<0.001). CONCLUSION: This long-term registry shows that stent thrombosis remains a major safety issue after PCI with stent implantation, with a significant prognostic impact. However, in the present work the risk of stent thrombosis was similar with either DES or BMS, suggesting thus that DES are not associated with any increase in long-term thrombotic risk in comparison to BMS.

Surfactant therapy for acute respiratory distress in children.

In children with acute lung injury the endogenous surfactant system is altered via a variety of different mechanisms, including inflammation, vascular dysfunction, oxidant injury, cellular injury and oedema. This article examines the pathophysiology of acute lung injury and surfactant use for treatment of acute respiratory failure in infants and children.

Functional imaging through scattering medium via fluorescence speckle demixing and localization.

Recently, fluorescence-based optical techniques have emerged as a powerful tool to probe information in the mammalian brain. However, tissue heterogeneities prevent clear imaging of deep neuron bodies due to light scattering. While several up-to-date approaches based on ballistic light allow to retrieve information at shallow depths inside the brain, non-invasive localization and functional imaging at depth still remains a challenge. It was recently shown that functional signals from time-varying fluorescent emitters located behind scattering samples could be retrieved by using a matrix factorization algorithm. Here we show that the seemingly information-less, low-contrast fluorescent speckle patterns recovered by the algorithm can be used to locate each individual emitter, even in the presence of background fluorescence. We test our approach by imaging the temporal activity of large groups of fluorescent sources behind different scattering phantoms mimicking biological tissues, and through a brain slice with a thickness of ~200 micron.

Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up.

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing. The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0-11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2-4.9) as major independent risk factors for recurrent wheezing. In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.

Sevoflurane inhalation for severe bronchial obstruction in infants with bronchiolitis.

Bronchiolitis is a lower respiratory tract viral infection which may result in severe bronchial obstruction and respiratory failure despite treatment with beta-adrenergic agonists and glucocorticoids. Here we describe two otherwise healthy infants with severe bronchiolitis whose clinical course was complicated by marked bronchial obstruction and respiratory acidosis refractory to conventional medications (ß-stimulants, anticholinergics and corticosteroids) and non-invasive positive pressure ventilation. Sevoflurane inhalation allowed both infants to attain a sustained, clinical improvement in ventilation and one patient to avoid mechanical ventilation. We suggest that sevoflurane inhalation may be a therapeutic option in the treatment of young infants with severe bronchiolitis who respond poorly to conventional therapy.

Neonatal molding in deformational auricolar anomalies.

INTRODUCTION: Congenital auricular anomalies can be categorized either as malformational or deformational. The first are characterized by a partial absence of the skin or cartilage resulting in a constricted or underdeveloped pinna and require surgical correction. Deformations are characterized by a misshaped but fully developed pinna and are best treated by auricular molding. AIM: Authors want to present their case load in treatment of infants affected by deformational auricolar anomalies and describe their techniques using early splinting for congenital auricular deformities, like prominent ear, lop ear, constricted ear, Stahl's ear. PATIENTS AND METHODS: Between 2009 to 2011, in Maxillo and Oral Surgery Unit, a nonsurgical technique was used to treat 22 ears affected by deformational anomalies in 12 patients soon after birth. Four patients were female. This kind of nonsurgical correction of the deformed auricle was performed on lop ears (n=6), constricted ears (n=8), prominent ears (n= 4), Stahl's ear (n=4). Children more than two months old were also excluded. The mean of treatment time was 5.5 weeks. RESULTS: according to the Authors and the parents 100% of treated auricles improved. Improving at the end of the molding treatment was observed in 18% of the auricles, but recurrence to one year of stopping treatment. There were not complications caused by this procedure. CONCLUSIONS: The nonsurgical molding has the advantage to correct at a very early age a cosmetic abnormality, giving a natural and in the most of the time a satisfactory results, with a prevalence rate of complications of much less than surgical corrections.

Calendula officinalis: A New Natural Host of Pseudomonas viridiflava in Italy.

In November 2010, small necrotic spots surrounded by chlorotic halos, which sometimes enlarged and coalesced to form large dead areas, were observed on leaves of marigold (Calendula officinalis L.) plants grown in the Medieval Garden at the Agricultural Faculty of Perugia (central Italy). Cream-colored bacterial colonies were consistently isolated on nutrient agar (NA) from the diseased leaf tissues. Four representative selected strains, which were gram negative, fluorescent on King's medium B, and had oxidative but not fermentative metabolism, were subjected to a pathogenicity test by inoculating 1-month-old marigold plants. To prepare the inoculum, the bacterial strains were grown on NA at 27°C for 24 h, suspended in sterile deionized water, and adjusted to 1 × 106 CFU/ml. Sterile water was used for control plants. Marigold leaves were infiltrated with a glass atomizer at high pressure, and plants were kept in a growth chamber at 22 to 24°C, 70 µE·m-2·s-1 illumination and 12-h light period, and 80% relative humidity. Small, water-soaked necrotic spots were observed 10 days after inoculation, and the bacterium with the same cultural features of the original strains was reisolated from inoculated plants. For bacterial identification, the four original strains and two reisolates were subjected to LOPAT tests. They were levan negative, oxidase negative, potato rot positive, arginine dihydrolase negative, and tobacco hypersensitive response positive. These results were similar to those obtained with the type strain LMG 2352T of Pseudomonas viridiflava (Burkholder) Dowson. When 16S rDNA was amplified with the universal primers, P0 (6-27f Escherichia coli) and P6 (1515-1495r E. coli), and digested with the endonucleases, SacI and HinfI as previously reported (2), an identical restriction profile was obtained for marigold strains and reisolates and P. viridiflava strains, LMG 2352T, LMG 2353, LMG 5397, and NCPPB 1382. A completely different profile was obtained for P. syringae pv. syringae LMG 1247T. The 16S rDNA (1,364 bp) and the gyrB (570 bp) sequences of two selected marigold strains (GenBank Accession Nos. JN406504 and JN406505; JN406506 and JN406507), amplified by using universal and previously reported PCR primers (3), respectively, shared 100% sequence identity with P. viridiflava (GenBank Accession Nos. HM190229 and AY606763) for 16S rDNA and gyrB gene, respectively. On the basis of biochemical, physiological, molecular, and pathogenicity tests, it was concluded that the bacteria isolated from marigold leaves are P. viridiflava. To our knowledge, this is the first report of C. officinalis as a natural host of P. viridiflava. The plant was previously reported as a host of the bacterium by artificial inoculation (1). References: (1) J. F. Bradbury. Guide to Plant Pathogenic Bacteria. CAB International, Egham, UK, 1986. (2) A. J. González et al. Appl. Environ. Microbiol. 69:2936, 2003. (3) E. M. Goss et al. Genetics 169:21, 2005.

Very long-term outcome of peripheral arterial disease in patients undergoing percutaneous coronary revascularization: a retrospective analysis.

AIM: Peripheral arterial disease (PAD) in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is a well known risk factor leading to an increased rates of stroke, cardiovascular death and myocardial infarction. Anyway there are few data on very-long term outcome (more than 1 year follow up) of PAD after stent implantation. We thus aimed to evaluate the influence of PAD on very long-term outcome of our PCI-population. METHODS: We retrospectively identified all patients undergoing PCI with stent implantation at our center between July 2002 and June 2004, and thus eligible for at least 4 years of follow-up. For the purpose of this study, we considered a diagnosis of PAD based on clinical evaluation and/or angiographic documentation. We adjudicated the following clinical events: death, myocardial infarction, repeat revascularization, and their composite (i.e. major adverse cardiac events, MACE). RESULTS; A total of 1008 patients were included, 109 with PAD and 899 Without PAD. Those with had more often diabetes (35% vs. 25%, P=0.002), hypertension (83% vs. 68%, P=0.001) and unfavorable basal clinical condition at the start of this study: past-Percutaneous Coronary Intervention (PCI) (30% vs. 22%, P=0.005), past-Coronary Artery Bypass Graft (CABG) (24% vs. 14%, P=0.001), ejection fraction (EF) <35% (14% vs. 7%, P=0.02) and chronic renal failure (CRF) (15% vs. 6%, P=0.002). In addiction patient with PAD were more likely to have chronic total occlusion (CTO) (36% vs. 25%, p=0.02) and unprotected left main (16% vs. 8%,P=0.01). Clinical outcome at the time of follow-up (4,42 ± 1,66 years) was as follow: Revascularization (53% vs. 37%, P=0.002), Cardiac death (21% vs. 13%, P=0.04), MACE (69% vs. 49%, p<.001). Independent predictors of MACE according to our survival analysis were: PAD (HR 1.31; 95% CI 1.01-1.69), Age >75 (HR 1.23; 95% CI 1-1.51), Chronic heart failure (HR1.72; 95% CI 1.19-2.5), Unprotected left main (HR 1.48; 95% CI 1.12-1.96). CONCLUSION: This long-term registry shows that PAD remains an important clinical condition that negatively influences the outcome of patients undergoing PCI with stent implantation in a very long-term follow-up period.

Short and long term outcome of percutaneous coronary intervention with drug eluting stent and bare metal stent in patients with chronic kidney disease.

AIM: Coronary artery disease represents the most important cause of mortality and morbidity in chronic kidney disease (CKD). Despite continuous improvements in percutaneous coronary intervention (PCI), CKD is still associated with more adverse events after PCI. We performed a retrospective study to compare bare metal stents (BMS) versus drug eluting stents (DES) in CKD. METHODS: We included consecutively all patients undergoing PCI at our Centre from July 2002 to December 2005 with CKD, defined as creatinine clearance <60 mL/min. Patients who received only DES were compared to those who received only BMS. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e. the composite of death, myocardial infarction and repeat revascularization). RESULTS: We included a total of 219 patients with CKD out of a total of 2354 patients, with 164 receiving BMS and 55 DES. After a mean follow up of 48 months, the MACE rate was significantly higher in BMS group (71% versus 38%, P<0.001). A similarly increased risk with BMS was found for death (45% versus 17%, P<0.001), whereas the rates for repeat coronary revascularization, myocardial infarction and stent thrombosis were not significantly different. Multivariable analysis showed that BMS vs.. DES implantation was not statistically significant associated with MACE, death, myocardial infarction, rePTCA or stent thrombosis. CONCLUSION: Compared with BMS, use of DES in patients with CKD is safe and effective in reducing adverse outcomes. However, differences found between groups in clinical end-point could be ascribed to selection bias and confounding factors.

Surfactant and non invasive ventilation for preterm infants.

Mechanical ventilation, although life-saving, predisposes preterm infants to BPD. NCPAP emerged as an alternative to invasive ventilation, but it fails in about 30% of infants even when coupled with surfactant therapy. Alternative modes of non invasive ventilation are currently used in neonatology in order to prevent mechanical ventilation. Among these, Synchronized Nasal Intermittent Positive Ventilation (SNIPPV) seems to ensure better results. (www.actabiomedica.it).

Detection of respiratory viruses in the 2009 winter season in Rome: 2009 influenza A (H1N1) complications in children and concomitant type 1 diabetes onset.

We investigated clinical characteristics and complications, particularly type 1 diabetes onset, in children hospitalized for 2009 pandemic influenza A (H1N1) virus and compared number of consultations, rate of hospitalization and virus identification in children hospitalized for acute respiratory symptoms (ARS) during the winter season 2009-2010 and 2004-2005. Patients were tested for 2009 H1N1 virus and 14 respiratory viruses on pharyngeal brush/nasal aspirates, using a RT-PCR or nested PCR assays. Consultations and hospitalizations were extracted from operative system GIPSE. The total number of consultations increased by 12%, consultation rate for ARS by 13% and number of hospitalizations by 56% from 2004-2005 to 2009-2010. In 2004-2005, Influenza A virus was identified in only 7 percent of hospitalized children, while in 2009-2010 the 2009 H1N1 virus was identified in 21%. Three children attending the hospital for ARS and 2009 H1N1 infection had ketoacidosis as the onset manifestation of type 1 diabetes. By comparing the number of new diabetes diagnoses among the two winter seasons, we found a higher number of new diagnoses in October 2009-January 2010 than in the same period in 2004-2005 (19 vs 10). Six children (13%), all presenting with pre-existing diseases, were admitted to the pediatric intensive care unit. No children died. The outbreak of this novel virus has increased pediatric consultation rates and hospitalizations compared with previous winters without causing deaths. The children at highest risk for severe infection are those with comorbidities. The 2009 H1N1 virus seems in some way involved in the pathogenesis of type 1 diabetes.

SOS1 over-expression in genital skin fibroblasts from hirsute women: a putative role of the SOS1/RAS pathway in the pathogenesis of hirsutism.

Hirsutism is the development of androgen-dependent terminal body hair in women in places in which terminal hair are normally not found. It is often associated with hyperandrogenemia and/or polycystic ovary syndrome (PCOS), but the existence of uncommom hirsutism forms that are not related to altered androgen plasma levels lead also to the definition of - idiopathic hirsutism. Although the pathophysiology of hirsutism has been linked to increasing 5-alpha reductase (SRD5A) activity and to an alteration of the androgen receptor (AR) transcriptional machinery, many aspects remain unclear. In particular, the relationships between androgens and local factors are poorly understood. In the present paper, we selected for a genital skin biopsy, 8 women affected with severe hirsutism (Ferriman-Gallway score greater than 25) but with normal plasma androgen levels, with the exception of slightly higher serum 3alpha-diol-glucuronide levels, and 6 healthy controls and analyzed their androgen- and insulin-specific transcriptional profile using a specific custom low density microarray (AndroChip 2, GPL9164). We identified the over-expression of the Son of Sevenless-1 (SOS1) gene in all of the hirsute skin fibroblast primary cell cultures compared to control healthy women. Since SOS1 is a guanine nucleotide exchange factor that couples receptor tyrosine kinases to the RAS signaling pathway that controls cell proliferation and differentiation, we further analyzed SOS1 expression, protein level and RAS signaling activation pathway in an in vitro model (NHDF, normal human dermal fibroblast cell line). NHDF treated for 24 h with different concentrations of DHT and T showed an increase in SOS1 levels (both mRNA and protein) and also an activation of the RAS pathway. Our in vivo and in vitro data represent a novel preliminary observation that factors activating SOS1 could act as local proliferative modulators linked to the androgen pathway in the pilosebaceous unit. SOS1 over-expression may play a role in the regulation of the RAS/mitogen-activated protein kinase pathway in the skin, in the hair follicle proliferation and cell cycle, suggesting new perspectives in understanding the pathogenesis of idiopathic hirsutism.

Percutaneous drug-eluting stent implantation in diabetic patients: short and long term outcomes from an observational study.

AIM: The introduction of drug-eluting stents (DES) has markedly improved mid-term results of percutaneous coronary intervention (PCI) in diabetics. However, it is unclear whether the risk-benefit balance of DES in diabetics is maintained also at long-term and in insulin-requiring patients. We thus aimed to appraise long-term outcomes of diabetic patients treated with PCI with DES, stratifying according to insulin therapy. METHODS: We retrospectively collected baseline, procedural and outcome data from all patients undergoing PCI with DES from July 2002 to June 2004 at our center. We distinguished three groups: insulin-requiring diabetics, non-insulin-requiring diabetics and patients without diabetes. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e. the composite of death, myocardial infarction, or target vessel revascularization). We also considered stent thrombosis according to the Academic Research Consortium Definition. RESULTS: We included a total of 1266 patients, with 3% of insulin-requiring diabetes, 22% with non-insulin-requiring diabetes, and 75% without diabetes. There were significant differences across groups in prevalence of male gender (respectively, 32.4%, 74.6% and 81%, P<0.001), and DES usage (54.1%, 34%, and 30.4%, P=0.007). Thirty-day MACE occurred with similar frequency in the three groups (8.1%, 7.3% and 6.3%, P=0.78), with death in 3%, 2%, and 1.4% (P=0.71) and myocardial infarction in 5.4%, 1.8% and 0.8% (P=0.02). After a median follow-up period of 58 months, MACE occurred in 59.5% of patients with insulin-requiring diabetes, in 50.6% of non-insulin-requiring diabetics and in 38.9% of non-diabetics (P<0.001). Death occurred in 24.3%, 17.5% and 8.5%, (P<0.001), myocardial infarction in 10.8%, 6.6%, and 5.1% (P=0.25), repeat revascularization in 46%, 31.6%, and 30% (P=0.11), and definite stent thrombosis in 0%, 1.1%, and 1.3% (P=0.78). CONCLUSION: Our study confirms the high risk profile of diabetic patients, especially when ischemic disease it is known. In this setting, diabetic and comorbidities fix the price not only in term of need of further revascularization, but mainly in survival decrease. It can be concluded that not only revascularization but also ­ and especially ­ comorbidities treatment plays a determinant role reducing follow-up events. Further research on additional pharmacologic treatments or hybrid revascularization strategies may mitigate the burden of morbidity and mortality.

Clopidogrel treatment in a patient with ticlopidine-induced hepatitis following percutaneous coronary stenting.

Thienopyridines are commonly prescribed antiplatelets drugs, extremely useful for the acute and chronic management of patients with cerebrovascular and cardiovascular diseases. The occurrence of their side effects is fortunately uncommon, although unpredictable. We thereby describe a case of prescription of clopidogrel in a patient with ticlopidine-induced hepatitis confirmed by liver biopsy that had undergone multiple percutaneous coronary stenting procedures necessitating subsequent compulsory antiplatelets treatment. The description of this exceptional clinical case is of relevant knowledge to orientate a physician treating a patient with absolute need of antiplatelets and history of previous drug-induced reactions.