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Background Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63, P = .01, respectively). Modeling with competing risks yielded for dense and total scar (AUC: 0.67 vs 0.61, P = .01 and AUC: 0.66 vs 0.61, P = .005, respectively). Conclusion In this analysis of the multicenter CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry, fully automatic machine learning-based late gadolinium enhancement analysis reliably quantifies myocardial scar mass and improves the current prediction model that uses guideline-based risk criteria for implantable cardioverter defibrillator implantation. ClinicalTrials.gov registration no.: NCT03352648 Published under a CC BY 4.0 license. Supplemental material is available for this article. ispartof: Radiology vol:307 issue:3 pages:e222239- ispartof: location:United States status: published

Due to the SARS-CoV-2 outbreak, wearing a disposable face mask has become a worldwide daily routine, not only for medical operators or specialized personnel, but also for common people. Notwithstanding the undeniable positive effect in reducing the risk of virus transmission, it is important to understand if a prolonged usage of the same face mask can have effectiveness on filtering capability and potential health consequences. To this aim, we present three investigations. A survey, carried out in central Italy, offers an overview of the distorted public awareness of face mask usage. A functional study shows how prolonged wearing leads to substantial drops in humid air filtration efficiency. Finally, a morphological analysis reports the proliferation of fungal or bacteria colonies inside an improperly used mask. Our study highlights therefore that wearing a face mask is really beneficial only if it is used correctly. Funding Agencies|Italian Ministry of University and Research (MUR) through the Sapienza University Project 2021 "SMART FACE-MASK FOR MONITORING HEALT-RELATED PARAMETERS IN THE BREATHING ZONE" [RG12117A84C979D3]; Regione Lazio; Fondo Europeo di Sviluppo Regionale (FESR) [1398 001-36723]; Italian Ministry of Foreign Affairs and International Cooperation (MAECI) [PGR00843]

The aim of this current study was to assess elbow ligament tears after dislocation using magnetic resonance imaging (MRI) and to correlate any pre-operative imaging with intra-operative findings of elbow ligament tears. We prospectively included 32 patients with acute elbow dislocation investigated by MRI at a means of five days from dislocation. A simple elbow dislocation was diagnosed in 14 patients (44%); associated bone injuries were identified in 18 elbows (56%). Surgical repair of elbow ligaments was carried out in 23 patients, and nine cases were treated non-operatively. A blinded MRI evaluation of all 32 elbows was performed by an orthopaedic surgeon (rater 1) and a musculoskeletal radiologist (rater 2). Inter-rater agreement for MRI evaluation of 32 was poor for lateral ulnar collateral ligament (LUCL) tears, fair for radial collateral ligament (RCL), moderate for annular ligament (AL), and fair for ulnar collateral ligament (UCL). All tears were reported as complete by rater 1; 13/32 partial tears were identified by rater 2 (LUCL = 2, RCL = 2, UCL = 9). Correlation between surgical and MRI findings showed good inter-rater agreement for LUCL and AL tears in both raters. Agreement for RCL tear was poor for rater 1 and fair for rater 2; agreement for UCL tear was fair for rater 1 and poor for rater 2. Intra-operative findings showed ten radial head fractures (RHFs) and ten coronoid fractures (CFs). LUCL tears were found in the four cases of type II RHFs and in 3/4 cases of CFs. Bone injuries and ligament tears were not significantly associated. MRI scan supported surgeons to identify soft tissue injuries and to address the most suitable surgical approach after acute elbow dislocation. Inter-observer agreement for intra-operative findings was high for LCL complex injuries and poor for UCL.

Cholangiocarcinoma (CC) accounts for about 3% of the gastrointestinal and 10-25% of all hepatobiliary malignancies. It arises from the epithelium of the bile duct and it can be classified in intrahaepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinoma, depending on the anatomical location. About 50-60% of the cases are PCC. Early detection is very difficult for the lack of symptoms, and most of the patients are not resectable at the time of diagnosis. IRE is a non-thermal ablation technique that determines cellular apoptosis by electrical impulses without involving extracellular matrix like MW or RF ablation (MWA and RFA). The aim of our study is to demonstrate the safety, feasibility and efficacy of this procedure in the treatment of cholangiocarcinoma according to our experience. From 2015 to 2019, fifteen patients with unre-sectable perhilar and intrahepatic colangiocarcinoma (7 female and 8 male, mean age 69.2) were referred to our department to be enrolled in our prospective study that was approved by local Ethical Committee. Eight lesions were defined iCC and seven of them pCC. Six patients had biliary STENT and four external percutaneous transhepatic biliary drainage (PTBD). The IRE procedure was performed to expert radiologist (G.B.) under CT guidance using the Nanoknife IRE device (Angiodynamics, Queensbury, NY). The data before and after treatment were compared using Wilcoxon Rank Test and the survival outcome was evaluated using Kaplan Meyer Test. All procedures performed under CT guidance have been successfully completed. Treated lesions were located seven perhilar and eight intrahepatic sites and showed a mean volume 66.3 (SD 70.9; IC ranged from 5.57 to 267.20 cm(3)). No major complications were observed. From 30 to 90 days, the mortality rate was around 0%. Progression of the disease in all cases were not observed. Only one patient was reported increase of the Ca19-9 without sign of pancreatitis and bile obstruction. The imaging follow-up showed the local disease control with a decrease of the entire volume of the lesion and a further reduction of the densitometric values. From the comparison between the mean volumes for each group (before and after treatment), the Wilcoxon Rank test demonstrated the statistical significant difference with a p value < 0.01. On the contrary, it is believed that this results encouraging in considering the IRE procedure the safe, feasible and effective method in the treatment of the CC

Perianal fistulas represent one of the most critical complications of Crohn’s disease (CD). Management and treatment need a multidisciplinary approach with an accurate description of imaging findings. Aim. This study aspires to assess the significative role of Magnetic Resonance Imaging (MRI) in the study of perianal fistulas, secondary extensions, and abscess in patients with CD. Therefore it is essential to standard-ize an appropriate protocol of sequences that allow the correct evaluation of disease activity and complica-tions. Methods: We selected and reviewed ten recent studies among the most recent ones present in literature exclusively about pelvic MRI imaging and features in CD. We excluded studies that weren’t in the English language. Conclusions: MRI has a crucial role in the evaluation and detection of CD perianal fistulas because, thanks to its panoramic and multiplanar view, it gives excellent anatomic detail of the anal sphincters. To-day MRI is the gold standard imaging technique for the evaluation of perianal fistulas, mainly because this technique shows higher concordance with surgical findings than does any other imaging evaluation. Surgical treatment is often required in the management of perianal fistula in patients with CD, which often have complex perineal findings. (www.actabiomedica.it).

Collagen filaments derived from the two marine demosponges Ircinia oros and Sarcotragus foetidus were for the first time isolated, biochemically characterised and tested for their potential use in regenerative medicine. SDS-PAGE of isolated filaments revealed a main collagen subunit band of 130 kDa in both of the samples under study. DSC analysis on 2D membranes produced with collagenous sponge filaments showed higher thermal stability than commercial mammalian-derived collagen membranes. Dynamic mechanical and thermal analysis attested that the membranes obtained from filaments of S. foetidus were more resistant and stable at the rising temperature, compared to the ones derived from filaments of I. oros. Moreover, the former has higher stability in saline and in collagenase solutions and evident antioxidant activity. Conversely, their water binding capacity results were lower than that of membranes obtained from I. oros. Adhesion and proliferation tests using L929 fibroblasts and HaCaT keratinocytes resulted in a remarkable biocompatibility of both developed membrane models, and gene expression analysis showed an evident up-regulation of ECM-related genes. Finally, membranes from I. oros significantly increased type I collagen gene expression and its release in the culture medium. The findings here reported strongly suggest the biotechnological potential of these collagenous structures of poriferan origin as scaffolds for wound healing.

OBJECTIVE Buccal myomucosal local flaps in oral cavity reconstruction are a valid option for small-to-moderate defects. Nevertheless, few articles report about functional recovery. The purpose of the present analysis is to evaluate the impact of these flaps on function and quality of life. STUDY DESIGN The study, retrospectively conducted on 36 patients who were surgically treated for tongue cancer between 2012 and 2018 at the Unit of Maxillo-Facial Surgery, Foundation IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (Italy), evaluates functional outcomes using the following 4 questionnaires: Performance Status Scale for Head and Neck Cancer Patients, M.D. Anderson Dysphagia Inventory, Speech Handicap Index, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module. RESULTS All patients are able to eat soft or more solid foods, and most of them eat quietly in public. Although 50% of cases reported a certain degree of dysphagia, it does not impact self-esteem and social relationships. Only 20% of patients have severe problems with speech. However, more than half of the cases (65%) report oral problems. CONCLUSIONS The collected data confirm the suitability of the myomucosal cheek flaps for tongue reconstruction. Most patients report a good functional recovery and satisfactory quality of life even if none of them has a recovery comparable to the presurgical state.

Ballistic traumas are defined by a projectile entering the body. Such projectiles include bullets, birdshot, and metal fragments from the covering or the contents of an explosive device. They frequently cause severe wounds characterized by a range of clinical pictures and a large spectrum of concomitant wounds. The major aims of imaging are to define the path of the projectile or projectiles, to evaluate which tissues have been injured, to estimate the severity of injury, and to determine what additional studies are needed. A routine radiograph is performed in patients with gunshot wounds. The diagnostic approach has been changed by the use of multidetector row computed tomography (MDCT) due to its technical developments particularly faster data acquisition and advanced image reconstructions. In the evaluation of patients with gunshot injuries, MDCT is considered the method of choice to identify hemorrhage, bullet, bone fragments, air, hemothorax, nerve lesions, musculoskeletal lesions, and vessel injuries. Moreover, MDCT technology and multiplanar reformation postprocessing allow meticulous trajectory analysis that potentially benefits the clinical outcomes of patients aiding time-saving triage and correct image-based diagnosis of organ and vessel damage. Familiarity of ballistics and forensic sciences will therefore help the radiologist in assessment and localization of the damage caused by projectiles.

It is debated whether percutaneous revascularization (PCI) of total coronary chronic occlusion (CTO) is superior to optimal medical therapy (OMT) in improving symptoms, left ventricular (LV) function and major adverse cardiac/cerebrovascular events (MACCE). Furthermore, CTO-PCI is a challenging technique, with lower success rate than in other settings. A systematic analysis of baseline LV function, infarction extent and ischaemic burden to predict response to revascularization has never been performed.To establish a CMR protocol to identify patients (pts) who can benefit most from CTO-PCI. Myocardial viability/ischaemia retains high biological plausibility as predictors of response to revascularization. Therefore, baseline viability (necrotic tissue extent, response to inotropic stimulation) and ischaemia (perfusion defect, wall motion abnormality during stress) will be studied as potential predictors of mechanical LV segmental improvement and ischaemic burden reduction in CTO territory (primary endpoint), LV remodelling and global function, Seattle Angina Questionnaire, and MACCE improvement (secondary endpoints) in the follow-up.Pts with CTO suitable for PCI undergo stress-CMR for viability/ischaemia assessment. Pts with normal LV function undergo adenosine, those with moderately-reduced ejection fraction (EF) and wall motion abnormalities high-dose dobutamine, pts with EF35% low-dose dobutamine. All pts undergo late gadolinium enhancement and repeat the same scan at 12 ± 3 months, regardless of PCI success or decision for OMT.A multi-parameter CMR protocol tailored on pts characteristics to study viability/ischaemia could help in identifying responders in terms of LV function, ischaemic burden and clinical outcome among pts suitable for CTO-PCI, improving selection of best candidates to percutaneous revascularization.

Background Clinical evaluation of stress perfusion cardiovascular magnetic resonance (CMR) is currently based on visual assessment and has shown high diagnostic accuracy in previous clinical trials, when performed by expert readers or core laboratories. However, these results may not be generalizable to clinical practice, particularly when less experienced readers are concerned. Other factors, such as the level of training, the extent of ischemia, and image quality could affect the diagnostic accuracy. Moreover, the role of rest images has not been clarified. The aim of this study was to assess the diagnostic accuracy of visual assessment for operators with different levels of training and the additional value of rest perfusion imaging, and to compare visual assessment and automated quantitative analysis in the assessment of coronary artery disease (CAD). Methods We evaluated 53 patients with known or suspected CAD referred for stress-perfusion CMR. Nine operators (equally divided in 3 levels of competency) blindly reviewed each case twice with a 2-week interval, in a randomised order, with and without rest images. Semi-automated Fermi deconvolution was used for quantitative analysis and estimation of myocardial perfusion reserve as the ratio of stress to rest perfusion estimates. Results Level-3 operators correctly identified significant CAD in 83.6% of the cases. This percentage dropped to 65.7% for Level-2 operators and to 55.7% for Level-1 operators (p

Emergency department assessment is a critical opportunity to identify elder abuse and violence against women, which represent a growing problem, requiring the attention of health care systems. Elder abuse is most frequently perpetrated by family members because of the higher levels of stress, burnout, and financial problems affecting the caregivers that can even lead to deadly consequences. Intimate partner violence is defined as physical, sexual, or psychological harm caused to another by a current or former partner or spouse, and can range from a single acute hit to chronic battering, varying in frequency and severity. Radiologists have a critical role in detecting those injury findings suggestive of abuse and violence. When appropriate, additional information about the social circumstances in which an injury took place, linked with imaging findings, may also be helpful in diagnosing abuse. The purpose of this article is to highlight the role of diagnostic imaging in the detection of lesions compatible with domestic abuse in elderly patients and women, and to allow the recognition of the alterations most frequently associated with this type of violence. (C) 2018 Published by Elsevier Inc.

Chondrosia reniformis is a common marine demosponge showing many peculiarities, lacking silica spicules and with a body entirely formed by a dense collagenous matrix. In this paper, we have described the identification of a new cytotoxic protein (chondrosin) with selective activity against specific tumor cell lines, from C. reniformis, collected from the Liguria Sea. Chondrosin was extracted and purified using a salting out approach and molecular weight size exclusion chromatography. The cytotoxic fractions were then characterized by two-dimensional gel electrophoresis and mass spectrometry analysis and matched the results with C. reniformis transcriptome database. The procedure allowed for identifying a full-length cDNA encoding for a 199-amino acids (aa) polypeptide, with a signal peptide of 21 amino acids. The mature protein has a theoretical molecular weight of 19611.12 and an IP of 5.11. Cell toxicity assays showed a selective action against some tumor cell lines (RAW 264.7 murine leukemia cells in particular). Cell death was determined by extracellular calcium intake, followed by cytoplasmic reactive oxygen species overproduction. The in silico modelling of chondrosin showed a high structural homology with the N-terminal region of the ryanodine receptor/channel and a short identity with defensin. The results are discussed suggesting a possible specific interaction of chondrosin with the Cav 1.3 ion voltage calcium channel expressed on the target cell membranes.

Marine demosponges of the Verongiida order are considered a gold-mine for bioinspired materials science and marine pharmacology. The aim of this work was to simultaneously isolate selected bromotyrosines and unique chitinous structures from A. aerophoba and to propose these molecules and biomaterials for possible application as antibacterial and antitumor compounds and as ready-to-use scaffolds for cultivation of cardiomyocytes, respectively. Among the extracted bromotyrosines, the attention has been focused on aeroplysinin-1 that showed interesting unexpected growth inhibition properties for some Gram-negative clinical multi-resistant bacterial strains, such as A. baumannii and K. pneumoniae, and on aeroplysinin-1 and on isofistularin-3 for their anti-tumorigenic activity. For both compounds, the effects are cell line dependent, with significant growth inhibition activity on the neuroblastoma cell line SH-SY5Y by aeroplysinin-1 and on breast cancer cell line MCF-7 by isofistularin-3. In this study, we also compared the cultivation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) on the A. aerophoba chitinous scaffolds, in comparison to chitin structures that were pre-coated with Geltrex™, an extracellular matrix mimetic which is used to enhance iPSC-CM adhesion. The iPSC-CMs on uncoated and pure chitin structures started contracting 24 h after seeding, with comparable behaviour observed on Geltrex-coated cell culture plates, confirming the biocompatibility of the sponge biomaterial with this cell type. The advantage of A. aerophoba is that this source organism does not need to be collected in large quantities to supply the necessary amount for further pre-clinical studies before chemical synthesis of the active compounds will be available. A preliminary analysis of marine sponge bioeconomy as a perspective direction for application of biomaterials and secondary bioactive metabolites has been finally performed for the first time.

Gout is the most common inflammatory arthritis and is increasing in prevalence and incidence in many countries worldwide. Dual Energy Computed Tomography (DECT) has a high diagnostic accuracy in established gout, but its diagnostic sensitivity is low in subjects with recent-onset gout. A meta-analysis of 17 studies showed a pooled sensitivity and specificity of 0.85 and 0.88, respectively. DECT is a useful diagnostic tool for patients with contraindications for joint aspiration or for those who refuse joint aspiration. This article aims to give an up to date review and summary of existing literature on the role and accuracy of DECT in the imaging of gout. (www.actabiomedica.it)

Echocardiography-derived measurements of maximum left ventricular (LV) wall thickness are important for both the diagnosis and risk stratification of hypertrophic cardiomyopathy (HC). Cardiac Magnetic Resonance (CMR) imaging is increasingly being used in the assessment of HC however, little is known about the relationship between wall thickness measurements made by the 2 modalities. We sought to compare measurements made with echocardiography and CMR and to assess the impact of any differences on risk stratification using the current European Society of Cardiology (ESC) guidelines. Maximum LV wall thickness measurements were recorded on 50 consecutive patients with HC. 69% of LV wall thickness measurements were recorded with echocardiography, compared to 69% from CMR (p

Marine sponges remain representative of a unique source of renewable biological materials. The demosponges of the family Ianthellidae possess chitin-based skeletons with high biomimetic potential. These three-dimensional (3D) constructs can potentially be used in tissue engineering and regenerative medicine. In this study, we focus our attention, for the first time, on the marine sponge Ianthella labyrinthus Bergquist &amp, Kelly-Borges, 1995 (Demospongiae: Verongida: Ianthellidae) as a novel potential source of naturally prestructured bandage-like 3D scaffolds which can be isolated simultaneously with biologically active bromotyrosines. Specifically, translucent and elastic flat chitinous scaffolds have been obtained after bromotyrosine extraction and chemical treatments of the sponge skeleton with alternate alkaline and acidic solutions. For the first time, cardiomyocytes differentiated from human induced pluripotent stem cells (iPSC-CMs) have been used to test the suitability of I. labyrinthus chitinous skeleton as ready-to-use scaffold for their cell culture. Results reveal a comparable attachment and growth on isolated chitin-skeleton, compared to scaffolds coated with extracellular matrix mimetic Geltrex&reg, Thus, the natural, unmodified I. labyrinthus cleaned sponge skeleton can be used to culture iPSC-CMs and 3D tissue engineering. In addition, I. labyrinthus chitin-based scaffolds demonstrate strong and efficient capability to absorb blood deep into the microtubes due to their excellent capillary effect. These findings are suggestive of the future development of new sponge chitin-based absorbable hemostats as alternatives to already well recognized cellulose-based fabrics.

Quartz is a well-known occupational fibrogenic agent able to cause fibrosis and other severe pulmonary diseases such as silicosis and lung cancer. The silicotic pathology owes its severity to the structural and chemo-physical properties of the particles such as shape, size and abundance of surface radicals. In earlier studies, we reported that significant amounts of surface radicals can be generated on crystalline silica by chemical aggression with ascorbic acid (AA), a vitamin naturally abundant in the lung surfactant, and this reaction led to enhanced cytotoxicity and production of inflammatory mediators in a macrophage cell line. However in the lung, other cells acting in the development of silicosis, like fibroblasts and endothelial cells, can come to direct contact with inhaled quartz. We investigated the cytotoxic/pro-inflammatory effects of AA-treated quartz microcrystals (QA) in human primary fibroblasts and endothelial cells as compared to unmodified microcrystals (Q). Our results show that, in fibroblasts, the abundance of surface radicals on quartz microcrystals (Q vs QA) significantly enhanced cell proliferation (with or without co-culture with macrophages), reactive oxygen species (ROS) production, NF-κB nuclear translocation, smooth muscle actin, fibronectin, Bcl-2 and tissue inhibitor of metalloproteinase-1 expression and collagen production. Contrariwise, endothelial cells reacted to the presence of quartz microcrystals independently from the abundance of surface radicals showing similar levels of cytotoxicity, ROS production, cell migration, MCP-1, ICAM-I and fibronectin gene expression when challenged with Q or QA. In conclusion, our in vitro experimental model demonstrates an important and quite unexplored direct contribute of silica surface radicals to fibroblast proliferation and fibrogenic responses.

Background Heart failure (HF) epidemic has increased need for accurate diastolic dysfunction (DD) quantitation. Cardiac MRI can elucidate left atrial (LA) phasic function, and accurately quantify its conduit contribution to left ventricular (LV) filling, but has limited availability. We hypothesized that the percentage of LV stroke volume due to atrial conduit volume (LACV), as assessed using 3D-echocardiography, can differentiate among progressive degrees of DD in HF patients. Methods and results Sixty-three subjects (66 ± 12 years) with DD and ejection fraction (EF) ranging 14–62 % underwent full-volume 3D-echocardiography. Simultaneous LA and LV volume curves as function of time (t) were calculated, with LACV as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{LACV}}\left( t \right) \, = \, \left[ {{\text{LV}}\left( t \right){-}{\text{LV minimum}}} \right] \, - \, \left[ {{\text{LA maximum }} - {\text{ LA}}\left( t \right)} \right]$$\end{document}LACVt=LVt-LV minimum-LA maximum-LAt, expressed as % of stroke volume. Patients were assigned to four (0–3, from none to severe) DD grades, according to classical Doppler parameters. In this population DD is linked to LACV, with progressively higher percentages of conduit contribution to stroke volume associated with higher degrees of DD (p = 0.0007). Patients were then dichotomized into no-mild (n = 26) or severe (n = 37) DD groups. Apart from atrial volume, larger (p

BACKGROUND Despite improvements in pharmacological and mechanical devices, the risk of periprocedural myocardial infarction (PMI) is still high, particularly in prothrombotic conditions. Hyperhomocysteinemia has been associated with enhanced platelet function, impaired endothelial function and prothrombotic status, thus increasing the risk of cardiovascular events. No study has, so far, investigated the relationship between homocysteine levels and the risk of periprocedural MI in patients undergoing percutaneous coronary intervention (PCI), and this is therefore the aim of the current study. METHODS In 1150 patients undergoing PCI, homocysteinemia was assessed at admission. Cardiac biomarkers were measured at intervals from 8 to 48 h after PCI. Periprocedural myonecrosis was defined by a troponin I increase to three times the upper limit of normal (ULN) or by 50% if elevated at the time of the procedure. PMI was defined as a CK-MB increase to three times the ULN or of 50% if elevated at the time of the procedure. RESULTS We grouped patients according to tertile values of homocysteine. Higher homocysteine levels were associated with older age (P

Item does not contain fulltext BACKGROUND: Previous reports have suggested an association between elevated fibrinogen and CAD. Few studies have so far investigated the impact of diabetes on fibrinogen levels and its association with coronary artery disease (CAD) and platelet reactivity in diabetic patients that are therefore the aims of the current study. METHODS: We measured fibrinogen in 3280 consecutive patients undergoing coronary angiography. Samples were collected at admission for fibrinogen levels assessment. Coronary disease was defined for at least 1 vessel stenosis >50% as evaluated by QCA. RESULTS: Diabetes was observed in 1201 out of 3280 patients. Diabetic patients were older with more hypercholesterolemia, hypertension, higher BMI, more renal failure, previous MI or coronary revascularization (p

Contains fulltext : 153289.pdf (Publisher’s version ) (Closed access) Leukocytes have been involved in the pathogenesis of atherosclerosis, and recent attention has been raised on eosinophils, that have been claimed for a wide number of cardiovascular pathologies, affecting endocardium, myocardium and vascular walls. However, few data have been reported so far on the relationship between absolute eosinophils count (AEC) and the prevalence and extent of coronary artery disease (CAD), that was the aim of present study. Consecutive patients undergoing non-urgent coronary angiography were included. Haematological parameters were measured at admission. Significant CAD was defined as at least 1 vessel stenosis >50 %, while severe CAD as left main and/or trivessel disease, as evaluated by Quantitative Coronary Angiography. Our population is represented by 3,742 patients, divided according to tertiles values of AEC (0.2 x 10(3)/microl). Higher eosinophils values were significantly associated to male gender, main established cardiovascular risk factors, previous percutaneous or surgical coronary revascularization, antihypertensive and antiplatelet therapy at admission but inversely with acute presentation. Higher AEC was directly related with platelets count (p < 0.001), haemoglobin levels (p = 0.02), white blood cells count (p = 0.02), higher serum creatinine (p < 0.001), triglycerides (p < 0.001) and glycosylated haemoglobin (p < 0.001), while inversely with HDL cholesterol (p < 0.001). AEC was associated with multivessel disease (p = 0.03), chronic occlusions (p = 0.01), in-stent restenosis (p = 0.002), while inversely with the presence of intracoronary thrombus (p < 0.001). A significant relationship was found between AEC and the prevalence of coronary artery disease (p = 0.049), but not for the extent of more severe LM/trivessel CAD (p = 0.31). At multivariate analysis no independent role of eosinophils was found for CAD (adjusted OR [95 % CI] = 1.02 [0.91-1.15], p = 0.70), or severe CAD (adjusted OR [95 % CI] = 0.99 [0.89-1.1], p = 0.9), even when considering separately acute and elective patients. In conclusion, among patients undergoing coronary angiography, higher eosinophils levels are not independently associated with the prevalence and extent of coronary artery disease, but appear confounded by their link with major cardiovascular risk factors.

MR imaging has been widely evaluated in the assessment of patients with recurrent or residual symptoms following meniscal surgery. Importantly, the causes of such symptoms may relate to failure or complication of the surgical procedure, a possible recurrent or residual meniscal tear, or may be related to other causes of joint symptoms, including tears of the contralateral meniscus, or local hyaline cartilage, or marrow abnormalities subjacent to or distant to the meniscal surgical site. The complex diagnostic issues involved in the MR imaging evaluation of the postoperative meniscus were identified in early MR imaging studies. The knowledge of the normal MR imaging appearance of the knee after the more common repair procedures will allow radiologists to recognize complications associated with such procedures. In this article, we discuss the MR imaging evaluation of the knee after meniscal surgery.

The current document was developed by the working group on the 'application of cardiac magnetic resonance' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical cardiac magnetic resonance applications and to inform cardiologists how to implement their clinical and diagnostic pathway with the introduction of this technique in the clinical practice. Appropriateness criteria were defined using a score system: score 1-3 = inappropriate (test is not generally acceptable and is not a reasonable approach for the indication), score 4-6 = uncertain (test may be generally acceptable and may be a reasonable approach for the indication but more research and/or patient information is needed to classify the indication definitively) and score 7-9 = appropriate (test is generally acceptable and is a reasonable approach for the indication).

Cardiac magnetic resonance (CMR) has emerged as a reliable and accurate diagnostic tool for the evaluation of patients with cardiac disease in several clinical settings and with proven additional diagnostic and prognostic value compared with other imaging modalities. This document has been developed by the working group on the 'application of CMR' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical applications of CMR and to inform cardiologists on how to implement their clinical and diagnostic pathways with the inclusion of this technique in clinical practice. The writing committee consisted of members of the working group of the Italian Society of Cardiology and two external peer reviewers with acknowledged experience in the field of CMR.

To define reference values of cardiac volumes, dimensions, and new morpho-functional parameters normalized for age, gender, and body surface area by cine-bSSFP (balanced steady-state free-precession) magnetic resonance (MR).We enrolled 308 healthy subjects subdivided by gender and by six age classes: class I,15-20 years; class II,20-30 years; class III,30-40 years; class IV,40-50 years; class V,50-60 years; and class VI60 years. Dimensional, volumetric and morpho-functional parameters of the left (LV) and right (RV) ventricles were measured using cine-bSSFP MRI at 1.5T.The LV and RV end-diastolic volume indexes (EDVi) were inversely related to age (P0.0001 r = -0.34 and P0.0001 r = -0.37, respectively). In addition, the LV mass index decreased with age (P = 0.0004, r = -0.21). The LV longitudinal shortening was not significantly different among groups: ≥15% in all populations (95% confidence interval [CI]: 16-31). The sphericity index measured in end-diastole was higher in females than in males (P0.03): the upper limit was 40% for males and 42% for females. The normality cutoff of LV global function index was ≥33% in males and ≥35% in females. The end-diastolic volume (EDV) of RV and LV was balanced (RV/LV ratio 0.85-1.15) without differences in the population. The LV EDV/mass was 1.0-1.8 in males and 1.0-2.1 in females.This study provides potential age- and gender-specific reference.2 J. Magn. Reson. Imaging 2017;45:1055-1067.

The interleukin-1 gene cluster occupies a 360kb region of chromosome 2q13 and contains nine homologous genes. These include agonists and antagonists of the parallel IL-1 and IL-36 systems, and IL1F7, the gene encoding IL-37. As the genes of the cluster are structurally and functionally related and have similar mRNA kinetics, we have sought evidence for gene induction-specific looping of chromatin in the IL-1 cluster by chromatin conformation capture (3C). We show here that IL1A, IL1B and IL1F7 regulatory regions come in close proximity in LPS stimulated cells but not in resting human monocytes. This suggests that IL1A, IL1B and IL1F7 are likely transcribed by the same transcription factory. One cardinal function of transcriptional Locus Control Region (LCR) is bringing map-distant activated genes into close physical proximity within the transcription factory. Our data show distant intergenic DNA segments are also in close proximity to the regulatory regions of the three genes. This may indicate that they are co-regulated and raise the possibility of a LCR within the cluster.

Background and aim Pro-thrombotic status and platelet hyperreactivity still represent an important challenge for periprocedural myocardial infarction (PMI) after coronary stenting. Hyperhomocysteinemia has been suggested to increase the risk of cardiovascular events. The genetic variant of methylenetetrahydrofolate reductase (MTHFR) 677 C > T has been associated to reduced function of the enzyme, thus inducing hyperhomocysteinemia. In our study we investigated whether MTHFR 677 C > T polymorphism is associated with increased risk of periprocedural MI in patients undergoing coronary stenting. Methods and results We included 778 patients undergoing PCI. Homocysteinemia and genetic status were assessed at admission for all patients. Myonecrosis biomarkers were dosed at intervals from 6 to 48 h, PMI was defined as CKMB increase by 3 times the ULN or 50% of pre-PCI value, periprocedural myonecrosis for troponin I increase by 3 times the ULN or by 50% of the baseline. As many as 521 patients carried the MTHFR-T allele. No difference was found for main demographical and clinical features nor for biochemistry parameters, but for higher rate of statins treatment ( p = 0.03) in T-carriers. Polymorphic patients displayed significantly higher levels of homocysteine ( p = 0.005), with additive effect of the mutated T-alleles. Angiographic and procedural features were similar according to genetic status. MTHFR677T was not associated with periprocedural myocardial infarction (adjusted OR = 0.97[0.67–1.4], p = 0.87) or myonecrosis (adjusted OR = 1.03[0.83–1.36], p = 0.82). Same results were found at subgroup analysis in higher-risk subsets of patients. Conclusion Our study showed that among patients undergoing PCI, MTHFR 677 C > T polymorphism is associated to higher homocysteine levels, but does not influence the risk of periprocedural myocardial infarction.

Periprocedural myocardial infarction (PMI) still occurs in a large amount of percutaneous coronary interventions (PCI), mainly due to increased platelet activation. Platelet size has been suggested as an indicator of enhanced reactivity and platelet distribution width (PDW) could reflect morphologic changes in platelets, therefore affecting their function and potentially increasing the risk of complications after coronary stenting. Aim of the present study was to evaluate the relationship between PDW and PMI. We included 1,300 consecutive patients undergoing PCI. Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined as troponin I increase by three times the ULN or by 50 % of an elevated baseline value, whereas PMI as CKMB increase by three times the ULN or 50 % of baseline. We grouped patients according to tertiles values of PDW (

We aimed to analyse the effects of combined strength and power training during the competitive season on physical fitness in high-level amateur football players. Sixteen male players (22.5 (SD 2.5) years, 1.79 (0.05) m, 76.8 (6.1) kg) from one team were randomly assigned to either a strength training (ST, N = 8) or a control (CON, N = 8) group. ST conducted lower extremity resistance exercises combined with plyometrics and/or sprints 2 × 30 min per week for 7 weeks. CON performed technical-tactical training during the same time period. Before and after training several physical fitness parameters were assessed: one-repetition maximum (1-RM, half squat), isometric peak strength and rate of force development (RFD, leg press), jump height (countermovement, CMJ, drop jump, DJ), sprint times, agility, and intermittent endurance. Large significant test × group interactions were found for 1-RM, CMJ, and DJ reactivity index with increases in CT relative to CON(+11 to 18%). Although not significant (P < 0.20), likely practically relevant effects were observed for isometric peak strength and RFD (+24 to 29%). We found no relevant interaction effects for agility, sprint times, and intermittent endurance. A 7-week in-season combined strength and power training program can improve relevant strength and jump parameters in high-level amateur football players.

Received 9 March 2011; Final revision 31 January 2012; Accepted 31 January 2012;first published online 24 February 2012SUMMARYSerological surveys for diphtheria were conducted in six European countries including CzechRepublic, Hungary, Ireland, Latvia, Luxembourg, Slovakia and one country outside Europe,Israel. For each country, a nationally representative population sample was collected across theentire age range and was tested for antibodies to diphtheria toxin. Although each nationallaboratory used its preferred assay, the results were all standardized to those of the in vitroneutralization test and expressed in international units (IU) which allowed comparative analysesto be performed. The results showed that increasing age is related to a gradual increase inseronegative subjects (

Multinuclear platinum complexes are characterized by a peculiar DNA binding mode and higher cytotoxic potency than the mononuclear complexes, and efficacy against a wide range of preclinical tumor models. To reduce the high irreversible plasma protein binding and improve the chemical and metabolic drug stability, novel bis-platinum complexes were designed starting from the parent compound CT-3610. The novel second-generation bis-platinum complexes utilize alkylcarboxylate as leaving groups to improve their pharmacokinetic and pharmacodynamic profiles, thus overcoming the limitations of the previously developed multinuclear compounds. The selected compounds [CT-47518 and CT-47463, respectively (bis-capronate) platinum and (bis-butyrate) platinum], have similar in vitro degradation kinetics in human and murine plasma and, above all, an increased stability when compared to CT-3610, particularly in human plasma. In addition, both compounds exhibited a marked cytotoxic potency as compared with cisplatin and oxaliplatin. Interestingly, they were capable of overcoming resistance mediated by DNA mismatch repair defects in different cellular models. The complexes showed marked antitumor efficacy in Pt-refractory tumor xenografts, with remarkable activity in terms of tumor growth inhibition and tumor growth delay. The improved stability profile in human plasma compared to early bis- and triplatinum complexes together with the marked activity in cellular systems as well as in in vivo models, make CT-47518 and CT-47463 attractive candidates for further development.

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR·HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions.

Descending necrotizing mediastinitis (DNM) is a relatively rare condition caused by downward spread of neck infections into the mediastinum. This infection previously had a much worse prognosis. In recent years, prompt computer topography (CT) diagnosis has been recommended. CT scan provides the earliest means of detecting DNM for optimal management and early surgical intervention. This paper provides an illustrated summary of our extensive clinical experience with DNM, involving 36 documented cases with CT over a 5-year period.

The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, may be of predictive and prognostic value for cardiovascular (CV) events. We evaluated the relationship of NLR with the prevalence and extent of coronary artery disease (CAD) in consecutive patients undergoing elective or urgent coronary angiography. Our population (n = 3738 patients) was divided into NLR quartiles. Higher NLR was associated with aging and established CV risk factors, previous percutaneous coronary revascularization, acute presentation, and more complex pharmacological therapy. The NLR was related to platelet count, white blood cell count, creatinine, glycemia, uric acid, and C-reactive protein (all P = .001) levels but inversely related to hemoglobin ( P < .001), total cholesterol ( P = .005), and triglycerides ( P < .001) levels. The NLR was associated with multivessel disease ( P < .001), anterior descending, right coronary arteries ( P < .001) or circumflex branch lesions ( P = .01), percentage of stenosis ( P < .001), coronary calcification ( P < .001), and intracoronary thrombus ( P < .001) but inversely with in-stent restenosis ( P < .001) and thrombolysis in myocardial infarction flow ( P = .04). The NLR was directly related to the prevalence of CAD ( P = .001) and severe CAD ( P < .001). In patients undergoing coronary angiography, the NLR is independently associated with the prevalence and severity of CAD.

Item does not contain fulltext BACKGROUND AND AIM: There has been a surge of interest in the cardiovascular effects of vitamin D (25(OH)D), preventing the processes leading to vascular wall degeneration and coronary artery disease (CAD). Gender differences have been suggested for vitamin D status, with a higher rate of deficiency occurring especially in post-menopausal women, increasing the risk of bone fractures and osteoporosis. However, to date, few studies have evaluated the differences in 25(OH)D levels according to gender and their impact on the extent of CAD, which was therefore the aim of the present study. METHODS AND RESULTS: In patients undergoing coronary angiography, fasting samples were collected for the assessment of 25(OH)D levels. Significant CAD was defined as at least one vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. Of the 1811 patients included, 530 (29.3%) were females, who displayed older age (p < 0.001), higher rate of renal failure (p < 0.001), hypertension (p = 0.05), treatment with angiotensin-receptor blockers (p = 0.03) and diuretics (p < 0.001), acute presentation (p < 0.001), higher platelet count (p < 0.001), glycosylated haemoglobin (p = 0.02) and cholesterol (p = 0.001), but an inverse relationship with smoking (p < 0.001), previous cardiovascular events (p < 0.001), treatment with statins and acetylsalicylic acid (ASA) (p < 0.001), body mass index (p = 0.002), haemoglobin (p < 0.001), leucocytes (p = 0.03) and triglycerides (p < 0.001). Female gender was associated with lower vitamin D levels (14.5 +/- 10.9 vs. 15.9 +/- 9.5, p = 0.007) and independently associated with severe vitamin D deficiency (41.9% vs. 30.4%, p < 0.001; adjusted odds ratio (OR) (95% confidence interval (CI)) = 1.42 (1.08-1.87), p = 0.01). Lower tertiles of vitamin D were associated with an increased prevalence and severity of CAD in females (adjusted OR (95% CI = 1.26 (1.10-1.44), p = 0.001 for CAD; adjusted OR (95% CI) = 1.6 (1.39-1.87), p < 0.001 for severe CAD). In males, vitamin D status was independently related to the prevalence (adjusted OR (95% CI) = 1.28 (1.02-1.61), p = 0.03) of CAD, but not the extent of CAD (adjusted OR (95% CI) = 1.02 (0.86-1.2), p = 0.84). CONCLUSION: Gender significantly affects vitamin D status. The lower 25(OH)D levels observed in females, as compared to males, play a more relevant role in conditioning the severity of CAD.

Item does not contain fulltext BACKGROUND: Alterations of glucose homeostasis have been reported to occur even in non-diabetic patients, thus increasing the risk of cardiovascular events and worsening the outcome after an acute myocardial infarction (AMI). Still debated is the role of impaired glucose control in patients undergoing percutaneous coronary intervention (PCI), as hyperglycemia, represents an important pro-thrombotic stimulus, increasing platelet reactivity and potentially procedural complications. Therefore, the aim of our study was to assess the association between glycosylated hemoglobin and periprocedural myocardial infarction (PMI) in non-diabetic patients undergoing PCI. METHODS: We included patients without history of diabetes undergoing elective PCI. PMI was defined as creatine kinase-MB increase by 3 times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as Troponin I increase by 3x ULN or 50% of baseline. RESULTS: Our population is represented by 1199 patients, who were divided according to tertile values of glycosylated hemoglobin (HbA1c). Higher HbA1c was associated with ageing (p

Lysophosphatidic acid, the substrate for lysophosphatidic acid acyltransferase β (LPAAT-β), is a well-studied autocrine/paracrine signaling molecule that is secreted by ovarian cancer cells and is found at elevated levels in the blood and ascites fluid of women with ovarian cancer. LPAAT-β converts lysophosphatidic acid to phosphatidic acid, which functions as a cofactor in Akt/mTOR and Ras/Raf/Erk pathways. We report that elevated expression of LPAAT-β was associated with reduced survival in ovarian cancer and earlier progression of disease in ovarian and endometrial cancer. Inhibition of LPAAT-β using small interfering RNA or selective inhibitors, CT32521 and CT32228, two small-molecule noncompetitive antagonists representing two different classes of chemical structures, induces apoptosis in human ovarian and endometrial cancer cell lines in vitro at pharmacologically tenable nanomolar concentrations. Inhibition of LPAAT-β also enhanced the survival of mice bearing ovarian tumor xenografts. Cytotoxicity was modulated by diacylglycerol effectors including protein kinase C and CalDAG-GEF1. LPAAT-β was localized to the endoplasmic reticulum and overexpression was associated with redistribution of protein kinase C-α. These findings identify LPAAT-β as a potential prognostic and therapeutic target in ovarian and endometrial cancer.

Biological activity of the IL-1 system depends on the balance between two proinflammatory proteins (IL-1alpha and IL-1beta) and the related anti-inflammatory protein, the IL-1 receptor antagonist (IL-1Ra). The genes for these proteins lie within 430 kb on human chromosome 2. Based on a clinical trial of human recombinant IL-1ra in rheumatoid arthritis, we tested whether IL-1 genotype might be related to the likelihood of response to anti-IL-1 therapy. A positive response was defined as a reduction of at least 50% in the number of swollen joints by week 24, following treatment with either 150 mg/day IL-1ra or placebo. The response rate to treatment, independent of genotype, was 48% (44/91). A highly significant association was found between carriage of the rarer allele at IL1A(+4845) and response to treatment (P=0.0009; OR=4.85 (1.85,12.70)). The response rate in patients carrying this allele was 63.4% compared with 26.3% in noncarriers. A weaker association was found for IL1B(+3954) (P=0.02). There was a highly significant interaction between treatment (150 mg/day or placebo) and the composite genotype across IL1A(+4845) and IL1B(+3954) (P=7.6 x 10(-5)). No associations with IL-1 genotypes were found in patients receiving placebo. Thus, a significant pharmacogenomic effect was found in the treatment of RA patients with recombinant IL-1ra.

To determine the value of helical computed tomography (CT) in the diagnosis, management and outcome of patients suspected of having descending necrotizing mediastinitis (DNM). Thirty-two patients with suspected DNM were submitted to contrast-enhanced single detector-row helical CT, four detector-row CT and 16 detector-row CT of the neck and chest. In 10/32 patients (group 1) no abnormality was observed in the neck or in the chest spaces on CT scan. These patients were all treated non-operatively. In 12/32 patients (group 2) CT showed the presence in the neck spaces of fluid collections, fasciitis, cellulitis, myositis, jugular vein thrombosis and lymphadenopathy; in all these patients the chest was unaffected. A cervical drainage was performed in ten patients. In the remaining ten patients (group 3), the neck infection involved the mediastinal spaces in all the cases and the pleural and pericardial spaces; CT findings included mediastinal cellulitis and fluid collections, pleural and pericardial effusions, venous thrombosis and lymphadenopathy. In these patients, a cervico-mediastinal drainage was performed and antibiotics were administered. The CT provides a highly accurate depiction of the presence and the spread of DNM. The CT findings and the extension of disease are important factors in order to predict for patient management and outcome.

Abdominal blunt trauma represents the main cause of death in people of age less than 40 years; the liver injury occurs frequently, with an incidence varying from 3 to 10%. Isolated hepatic lesions are rare and in 77-90% of cases, lesions of other organs and viscera are involved. Right hepatic lobe is a frequent site of injury, because it is the more voluminous portion of liver parenchyma; posterior superior hepatic segments are proximal to fixed anatomical structures such as ribs and spine that may have an important role in determining of the lesion. The coronal ligaments' insertion in this parenchymal region augments the effect of acceleration-deceleration mechanism. Associated lesions usually are homolateral costal fractures, laceration or contusion of the inferior right pulmonary lobe, haemothorax, pneumothorax, renal and/or adrenal lesions. Traumatic lesions of left hepatic lobe are rare and usually associated with direct impact on the superior abdomen, such as in car-crash when the wheel causes a compressive effect on thorax and abdomen. Associated lesions to left hepatic lobe injuries correlated to this mechanism are: sternal fractures, pancreatic, myocardial, gastrointestinal tract injuries. Lesions of the caudal lobe are extremely rare, usually not isolated and noted with other large parenchymal lesions. The Institution of Specialized Trauma Centers and the technical progress in imaging methodology developed in the last years a great reduction of mortality. New diagnostic methodologies allow a reduction of negatives laparotomies and allow the possibility of conservative treatment of numerous traumatic lesions; however, therapy depends from imaging findings and clinical conditions of the patient. Computed tomography (CT) certainly presents a large impact on diagnosis and management of patients with lesions from blunt abdominal traumas. It is important to establish a prognostic criteria allowing decisions for conservative or surgical treatment; CT findings and peritoneal fluid evaluation may be used to make a first differentiation of severity of lesions, but haemodynamic parameters may help the clinician to prefer a conservative treatment. In emergency based hospitals and also in our experience, positive benefits spring from diagnostic accuracy and consequent correct therapeutic management.

Great interest has been focused in the last year on genetic predictors of cardiovascular risk. Glycoprotein IIb/IIIa (GP IIb/IIIa), fibrinogen receptor, is the final common pathway for aggregation and a key point for atherothrombosis. A single nucleotide polymorphism of IIIa subunit (Leu33Pro-PlA(1)/PlA(2) allele) has been suggested to increase aggregation and adhesion, however, contrasting reports have been reported so far on its effects on coronary artery disease (CAD). Aim of the current study was to perform a large meta-analysis including cohorts of patients undergoing coronary angiography in order to evaluate whether this polymorphism is associated with coronary artery disease. Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions abstracts were scanned for data of consecutive cohorts of patients undergoing coronary angiography, where PlA genotype was assessed. Primary endpoint was the prevalence of CAD. Secondary endpoint was severity of CAD defined as prevalence of multivessel disease (≥2 vessels). Data from seven studies were extracted, including a final number of 6700 patients. Among them 1893 (28.3%) carried the PlA(2) polymorphism, 163 of them in homozygosis. Angiographically defined CAD was present in 3573 (74.3%) PlA(1)/PlA(1) patients and in 1430 (75.5%) PlA(2) carriers. PlA(2) polymorphism was not associated with an increased prevalence of coronary artery disease, (OR [95% CI] = 1.07 [0.95-1.21], p = 0.28, pheterogeneity = 0.39). Similar results were obtained for multivessel disease (OR [95% CI] = 1.07[0.95-1.20], p = 0.27, pheterogeneity = 0.12). Meta-regression analysis demonstrated a significant inverse relationship between the risk of CAD among the PlA(2) carriers and ageing (r = -0.044, (-0.09, -0.0008), p = 0.046). Present meta-analysis demonstrates that 33Leu → Pro substitution of GPIIIa does not influence the prevalence and extent of angiographically defined coronary artery disease in general population, although apparently playing a role among younger patients.

Periprocedural myocardial infarction still occurs in patients undergoing percutaneous coronary intervention. However, very little is known about the role of biomarkers possibly predicting this complication. Serum uric acid has been associated with enhanced inflammatory status, higher thrombotic risk and poorer outcome after percutaneous coronary intervention. We therefore, evaluated the association between uric acid levels and periprocedural myocardial infarction in patients undergoing percutaneous coronary intervention.We evaluated 1272 consecutive patients undergoing percutaneous coronary intervention. We measured myonecrosis biomarkers at intervals from 8 to 48 h after percutaneous coronary intervention. Periprocedural myonecrosis was defined as a troponin I increase by 3 times the upper limit normal (ULN) or by 50% of an elevated baseline value and periprocedural myocardial infarction as creatine kinase-Myocardial Band increase by 3 times the ULN or 50% of baseline.Patients were divided according to tertile values of uric acid (5.40, ≥ 6.70 mg/dL). Serum uric acid was related to age, male gender, hypertension, smoking, renal failure (p0.001), previous coronary artery bypass grafts (p = 0.05), therapy with ACE inhibitors (p = 0.001) and diuretics (p0.001), glycaemia (p = 0.001), creatinine (p0.001), haemoglobin (p = 0.002) and white blood cells (p = 0.02). Serum uric acid was inversely related to type C lesions (p = 0.03) and coronary thrombus (p = 0.02). SUA did not affect the risk of periprocedural myocardial infarction (p = 0.29; adjusted odds ratio = 1.11[0.93-1.32], p = 0.26) or periprocedural myonecrosis (p = 0.97; adjusted odds ratio = 0.99[0.86-1.14], p = 0.89). Results were confirmed at subgroup analyses of higher-risk subsets of patients.This is the first large study showing that serum uric acid is not associated with an increase in the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary revascularization.

Diabetic patients undergoing percutaneous coronary interventions are still regarded as a very high risk category because of an increased platelet reactivity and risk of complications, especially in patients with inadequate glycaemic control. However, although its prognostic effect on long-term outcome is well-defined, still unclear is the effect of diabetes on the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary interventions, which was therefore the aim of our study.Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after nonemergent percutaneous coronary interventions. Periprocedural myocardial infarction was defined as creatine kinase-MB increase by three times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as troponin I increase by three times the upper limit normal or 50% of baseline.Of 1311 patients, diabetes mellitus was found in 458 patients (34.9%) and associated with age (p = 0.03), hypertension (p 0.001), renal failure (p = 0.01), previous MI (p = 0.03), previous coronary revascularization (p 0.001), higher fasting glycaemia and lower haemoglobin (p 0.001), more severe coronary disease (p 0.001), multivessel percutaneous coronary interventions (p = 0.03), coronary calcification (p = 0.003) and in-stent restenosis (p 0.001) but lower presence of thrombus (p = 0.03). Diabetic patients were receiving significantly more frequent specific pharmacological treatment at admission. Diabetic status did not influence the risk of periprocedural myocardial infarction or periprocedural myonecrosis [adjusted OR(95%CI) = 0.90(0.64-1.27), p = 0.57 and adjusted OR(95%CI) = 0.92(0.70-1.21), p = 0.55]. Amongst diabetic patients, we did not observe any effect of chronic glycaemic control on periprocedural myocardial infarction.Diabetic status, independent of chronic glycaemic control, is not associated with increased risk of periprocedural myocardial infarction and myonecrosis in patients undergoing percutaneous coronary interventions.

The interaction between mineral structures and living beings is increasingly attracting the interest of research. The formation of skeletons, geomicrobiology, the study of the origin of life, soil biology, benthos biology, human and mammalian diseases generated by the inhalation of dust and biomaterials are some examples of scientific areas where the topic has a relevance. In this chapter we focus on cell reactivity to siliceous rocks and to the various forms of silicon dioxide, in particular. The examples here reported carefully review how such minerals may strongly affect different living beings, from simple ones to humans. The biomineralogy concept is explained, focusing on the effects of rocks on cell growth and development. The toxic action of silicon dioxide in mammalian lungs is the oldest evidence of crystalline silica bioactivity. More recently, we could demonstrate that crystalline silica has a deep impact on cell biology throughout the whole animal kingdom. One of the most illustrative case studies is the marine sponge Chondrosia reniformis, which has the amazing ability to incorporate and etch crystalline silica releasing dissolved silicates in the medium. This specific and selective action is due to the chemical reaction of ascorbic acid with quartz surfaces. One consequence of this is an increased production of collagen. The discovery of this mechanism opened the door to a new understanding of silica toxicity for animal cells and mammalian cells in particular. The presence of silica in sea water and substrates also affects processes like the settlement of larvae and the growth of diatoms. The following sections review all such aspects.

Item does not contain fulltext BACKGROUND: Contrast induced nephropathy (CIN) is a complication of coronary angiography/percutaneous intervention (PCI). It is known that diabetes is an independent risk factor for CIN, but we have no data regarding the association between CIN and glycemic levels in patients without diabetes. Aim of our study was to evaluate whether high level of glycated-haemoglobin in patients without diabetes is associated with an increased risk of CIN. METHODS: A total of 1324 patients without diabetes, undergoing elective/urgent coronary angiography/angioplasty were divided according to quartiles of baseline glycated-haemoglobin. CIN was defined as an absolute >/=0.5mg/dL or a relative >/=25% increase in creatinine level at 24-48h after the procedure. RESULTS: Patients with elevated glycated-haemoglobin were older, with hypertension, metabolic syndromes, previous history of AMI, PCI and CABG. They had higher gycaemia, fasting-glycaemia and triglycerides but lower HDL-cholesterol. Patients with higher glycated-haemoglobin were more often on therapy with statins, diuretics and calcium-antagonist at admission, had higher basal, 24 and 48h creatinine, lower creatinine clearance and lower ejection fraction. They had the highest incidence of PCI and contrast volume-eGFR rate. CIN occurred in 10.6% of patients with a linear association with glycated-haemoglobin (p=0.001). No relationship was found between glycaemia/fasting glycaemia at admission and CIN. The multivariate analysis confirmed the association between elevated glycated haemoglobin (above the median value 5.7%) and the risk of CIN after adjustment for baseline confounding factors (Adjusted OR [95% CI]=1.69 [1.14-2.51], p=0.009). In fact, the results were consistent in major high-risk subgroups. CONCLUSION: This is the first study showing that among patients without diabetes undergoing coronary angiography/PCI elevated glycated-haemoglobin but not glucose levels is independently associated with the risk of CIN.

Background & Aims: The interleukin 1 receptor antagonist gene allele 2 has been suggested as a determinant of both disease susceptibility and extent in ulcerative colitis. The aim of this study was to assess the allele as a predictor of both the indication for colectomy and the occurrence of pouchitis after ileal pouch–anal anastomosis formation. Methods: Genotyping for the +2018 single nucleotide polymorphism in the interleukin 1 receptor antagonist gene was performed in 109 patients who had undergone colectomy, including 82 patients who had been followed prospectively after ileal pouch–anal anastomosis formation. Results: Patients with pouchitis had a higher allele 2 carriage rate compared with those without pouchitis (72% vs. 45%) and Kaplan–Meier survival analysis showed that allele 2 carriers had a significantly increased incidence of pouchitis compared with noncarriers (log-rank test, 6.5). After adjustment for confounding covariates in a Cox proportional hazards model, the relative hazard was 3.1 (95% confidence interval [CI], 1.2–7.8; P = 0.02). Although there was a higher allele 2 carriage rate in patients with chronic refractory compared with acute severe ulcerative colitis (63% vs. 48%), this difference was not significant (odds ratio, 1.9; 95% Cl, 0.9–4.1; P = 0.1). Conclusions: The interleukin 1 receptor antagonist gene allele 2 predicts pouchitis after ileal pouch-anal anastomosis in ulcerative colitis. GASTROENTEROLOGY 2001;121:805-811

The penton base of adenovirus mediates viral attachment to integrin receptors and particle internalisation, properties that can be exploited to reengineer prokaryotic viruses for the infection of mammalian cells. We report that filamentous phage displaying either the full-length penton base gene or a central region of 107 amino acids on their surface were able to bind, internalise, and transduce mammalian cells expressing integrin receptors. Both phage bound alphavbeta3, alphavbeta5, alpha3beta1, and alpha5beta1 integrin subtypes. Cell-binding was shown by electron microscopy; internalisation was investigated by immunofluorescence and confirmed by micropanning. As it has been described for adenovirus, pharmacologic disruption of phosphoinositide-30H kinase, but not of myosin light-chain kinase, inhibited phage internalisation. Recombinant phage encoding an eukaryotic expression cassette was able to mediate gene expression in mammalian cells. Taken together, these data open insights for the exploit of recombinant phage for integrin-targeted gene delivery.

Fibrosing alveolitis (FA) is characterized by persistent inflammation and elevated production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1ra) in the lung. Single base variations at position +2018 in the IL-1ra gene (IL-1RN) and position -308 in the TNF-alpha gene (TNF-A) are overrepresented in other chronic inflammatory disease populations. We have tested the hypothesis that predisposition to FA may also be influenced by these polymorphisms by genotyping 88 cases and matched controls from England and 61 cases and 103 unmatched controls from Italy. The rarer allele for IL-1RN and TNF-A was designated allele 2 in each case. For IL-1RN allele 2, in the English group, the relative odds of FA were increased in homozygous subjects by an odds ratio (OR) of 10.2 (95% confidence intervals [CI], 1.26 to 81.4; p = 0.03) and for carriers by an OR of 1.85 (95% CI, 0.94 to 3.63; p = 0.075). In the Italian population, the risk of FA was increased, in IL-1RN allele 2 homozygotes (OR, 2.54; 95% CI, 0.68 to 9.50; p = 0.2) and in carriers (OR 2.40; 95% CI, 1.26 to 4.60; p = 0.008). Carriage of TNF-A allele 2 was also associated with increased risk of FA in the English (OR, 1.85; 95% CI, 0.94 to 3.63; p = 0.075) and Italian (OR, 2.50; 95% CI, 1.14 to 5.47; p = 0.022) populations. These data suggest IL-1RN (+2018) allele 2 and TNF-A (-308) allele 2 confer increased risk of developing FA and, therefore, that unopposed IL-1beta and/or excessive TNF-alpha may play a pathophysiologic role in this condition.

Alopecia areata (AA) is a chronic inflammatory disease characterised by patchy hair loss with T cell infiltration of hair follicles. AA occurs in approximately 0.1% of the general population, but this is increased to 9% in Down syndrome (DS). DS is associated with an additional copy (full or partial) of chromosome 21, and the DS region may potentially include genes involved in the pathogenesis of AA. MX1 is the gene encoding the interferon-induced p78 protein (MxA). MxA protein confers resistance to influenza viruses, and we have previously shown that MxA protein is strongly expressed in lesional anagen hair bulbs from patients with AA but not in normal follicles. We therefore studied the possible involvement of MX1 in the pathogenesis of AA. To establish markers in the MX1 region which could be screened by PCR-based methods, we defined the human MX1 exon/intron organisation and screened the exons and the introns by conformation-sensitive gel electrophoresis. We found that the MX1 gene contains 17 exons extending over 33 kb. The size and sequence of the region from exon 6 to exon 16 are highly conserved between human and mouse. Screening of 4747 bp within the MX1 gene revealed four single nucleotide polymorphisms in intron 6. These polymorphisms are concentrated within 147 bp and show strong linkage disequilibrium. In a case-control association study for the MX1 (+9959) polymorphism in 165 AA patients and 510 controls we found a significant association of this marker with AA (odds ratio 1.79, 95% CI 1.21-2.66, chi2 = 8.464, P = 0.0036). The risk of disease was greater for patchy AA (mild disease) and with early age at onset (odds ratio 2.34, 95% CI 1.24-4.43, P = 0.0072), providing new evidence of genetic heterogeneity in AA. Our demonstration of genetic association between the MX1 gene and disease supports the hypothesis that this is a new candidate gene in AA.

Polymorphisms in the interleukin-1 (IL-1) gene cluster have been associated with an increased risk of developing certain diseases. A specific composite genotype of IL-1A and IL-1B polymorphisms, consisting of allele 2 of both IL-1A +4845 and IL-1B +3954 (formerly +3953) has been associated with an increased risk of severe adult periodontitis. Approximately 30% of the European population carry this genotype. The prevalence of the above IL-1A and IL-1B composite genotype in populations of different ethnic origins is unknown. Therefore, the primary aim of this study was to determine the prevalence of the IL-1 composite genotype in individuals of Chinese heritage, since epidemiologic studies indicate that periodontitis is widespread among ethnic Chinese. An additional aim was to evaluate if there was an association between the composite genotype and the severity of periodontal disease.A convenience sample of 300 volunteers of Chinese heritage (ages 21 to 69 years) received a periodontal examination including full-mouth clinical attachment loss measurements, probing depths, plaque index scores, and bleeding on probing. Blood was collected from a fingerstick and placed on a blotting paper card. The blood samples were analyzed for IL-1A +4845 and IL-1B +3954 polymorphisms using polymerase chain reaction (PCR)-based methods.Only 7 of the 300 subjects (2.3%) carried the composite IL- 1 genotype consisting of allele 2 of both IL-1A +4845 and IL-1B +3954. Allele 2 of the IL-1A +4845 polymorphism was carried by 17.0% (51/300) of the subjects; of these, only 2 were homozygous. Allele 2 of the IL-1B +3954 polymorphism was much rarer with only 3.3% (10/300) of the study population carrying this marker. All of the people who carried the IL-1B polymorphism were heterozygous. Too few of the subjects were positive for the IL-1 composite genotype to establish any relationship with the susceptibility to periodontitis.It was concluded that the prevalences of both IL-1A and IL-1B polymorphisms are dramatically lower in Chinese than those reported for Europeans. Findings from this study bring into question the usefulness of the composite genotype of allele 2 of both IL-1A +4845 and IL-1B +3954 as a method for determining the susceptibility of Chinese patients to adult periodontitis.