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Written culture in high and late medieval Scandinavia is characterized by a long and complex relationship between the Latin written tradition and the older native runic one. One product of the intersection of these traditions are several epigraphs where Latin, vernacular, Latin alphabet, and runes are combined. The aim of this paper is to propose a framework for analysing such bilingual and biscriptal inscriptions which takes into account two fundamental aspects of language and script choice: (1) the literacy of those involved in the production and reception of the texts, and (2) the role of the indexicality of languages and scripts in the shaping and representation of identities. The paper draws on epigraphic analyses and modern sociolinguistic approaches to written multilingualism and shows that an interdisciplinary method can further our understanding of the relationship between the Latin and vernacular written cultures, their status relative to each other, and their social functions in medieval Scandinavia.

Aims Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). Methods and results Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) Conclusion RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.

Background: Inflammation plays a key role in atrial fibrillation (AF). Epicardial adipose tissue around the atrial wall can influence atrial morpho-functional properties. The aim of this study was to assess whether an increased quantity and/or density of adipose tissue located around the left atrium (Fat-LA) are related to AF, independently from atrial size. Methods: eighty patients who underwent AF ablation and 80 patients without history of AF were selected. The Fat-LA mass was quantified as tissue within −190 to −30 Hounsfield Units (HU) on cardiac computed tomography angiograms (CCTA), and the mean adipose tissue attenuation was assessed. Results: Adipose tissue mass was higher in patients with AF (5.42 ± 2.94 mL) versus non-AF (4.16 ± 2.55 mL, p = 0.007), but relative fat quantity did not differ after adjusting for atrial size. Mean fat density was significantly higher in AF (−69.15 HU) versus non-AF (−76.82 HU, p < 0.0001) participants. In the logistic regression models, only the addition of mean Fat-LA attenuation led to a significant improvement of the model’s chi-square (from 22.89 of the clinical model to 31.69 of the clinical and adipose tissue attenuation model, p < 0.01) and discrimination (AUC from 0.775 to 0.829). Conclusions: Fat-LA volume is significantly greater only in absolute terms in patients with AF, but this difference does not hold after adjusting for the larger LA of AF subjects. On the contrary, a higher Fat-LA density was associated with AF, independently from LA size, providing incremental value over other variables that are associated with AF.

It has been demonstrated that Software exploitable Hardware Trojan Horses (HTHs) can be inserted in commercial CPUs and memories. Such attacks allow malicious users to run their own software or to gain unauthorized privileges over the system. As a consequence, HTHs must nowadays be considered a serious threat not only from academy but also from industry. In this paper we present a security checking module meant to be connected between the microprocessor and the instruction memory in order to monitor the fetching activity with the aim of detecting the activation of HTHs. In particular, we aim at detecting those HTHs that alter the expected execution flow by launching a malicious program. We integrated the proposed security checking module within a case study system based on a RISC-V microprocessor implemented on an FPGA and running a set of software benchmarks. This experiment demonstrated that our proposal is able to detect 100% of possible HTHs activations with no false alarms. We measured a LUT overhead of 0.5% and a FF overhead of 0.3%, with a 2.36% power consumption increase and no working frequency reduction.

Two articles this week focus on Erdheim-Chester disease (ECD), a rare histiocytosis that mainly affects adults. Clonal somatic mutations primarily involving proteins in the BRAF and MPAK pathways have established ECD as a myeloid neoplasm, with targeted therapies now available for patients. In the first paper, an international panel presents new consensus recommendations for evaluation and treatment of ECD. In the second paper, Pegoraro and colleagues present long-term outcomes of patients with ECD treated with sirolimus, with responses in patients both with and without BRAF mutations.

Objective: Chronic periaortitis (CP) is a rare fibro-inflammatory disorder that incorporates idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysms, and perianeurysmal retroperitoneal fibrosis. CP is included in the spectrum of IgG4-related disease. Since CP patients rarely undergo diagnostic biopsies, serum IgG4 levels are often used to classify CP as IgG4-related. However, the clinical and prognostic significance of serum IgG4 in CP is unknown. Methods: We measured serum IgG4 in active CP patients and compared the clinical characteristics, response to therapy and outcome of patients with high and normal levels. We also tested the diagnostic significance of IgG4 by comparing its levels in CP patients, healthy and disease controls (malignancies, Erdheim-Chester disease, large-, and small-vessel vasculitis). Results: We studied 113 consecutive patients with active CP. Twenty-four (21.2%) had high serum IgG4 (>135 mg/dL). The demographic, laboratory, and clinical characteristics of patients with high and normal IgG4 were similar, and so were the rates of ureteral obstruction and the disease characteristics on CT, MRI, and 18F-FDG-PET. Patients with high IgG4 only had a higher frequency of extra-retroperitoneal fibro-inflammatory lesions (p = 0.005). There were no significant differences in response to therapy and relapses between the two groups. Serum IgG4 levels did not discriminate CP from controls. Conclusions: Serum IgG4 levels are high in a minority of CP patients and do not identify specific clinical or prognostic subgroups; only a higher frequency of extra-retroperitoneal lesions is found in high-IgG4 patients. Serum IgG4 levels do not help in the differential diagnosis between CP and its mimics.

To the editor: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (

The extra domain A (ED A) of fibronectin has been identified as a tumor vessel specific neovascular marker in glioma. Antibody based vascular targeting against ED A of fibronectin allows precise accumulation of photosensitizer in glioma microvasculature and thereby promises to overcome drawbacks of current photodynamic therapy (PDT) for glioma treatment. Our aim was to characterize microcirculatory consequences of F8-small immunoprotein (SIP) mediated PDT by intravital microscopy (IVM) and to analyze the effects on glioma growth. For IVM SF126 glioma cells were implanted into dorsal skinfold-chamber of nude mice. PDT was performed after intravenous injection of photosensitizer (PS)-coupled F8-SIP or PBS (n = 4). IVM was performed before and after PDT for 4 days. Analysis included total and functional (TVD, FVD) vessel densities, perfusion index (PI), microvascular permeability and blood flow rate (Q). To assess tumor growth SF126 glioma cells were implanted subcutaneously. PDT was performed as a single and repetitive treatment after PS-F8-SIP injection (n = 5). Subcutaneous tumors were treated after uncoupled F8-SIP injection as control group (n = 5). PDT induced microvascular stasis and thrombosis with reduced FVD (24 h: 115.98 ± 0.7 vs. 200.8 ± 61.9 cm/cm(2)) and PI (39 ± 11 vs. 70 ± 10 %), whereas TVD was not altered (298 ± 39.2 vs. 278.2 ± 51 cm/cm(2)). Microvascular dysfunction recovered 4 days after treatment. Microvascular dysfunction led to a temporary reduction of glioma growth in the first 48 h after treatment with complete recovery 5 days after treatment. Repetitive PDT resulted in sustained reduction of tumor growth. F8-SIP mediated PDT leads to microvascular dysfunction and reduced glioma growth in a preclinical glioma model with recovery of microcirculation 4 days after treatment. Repetitive application of PDT overcomes microvascular recovery and leads to prolonged antiglioma effects.

Introduction: Clinical application of antiangiogenic therapy lacks direct visualization of therapy efficacy and vascular resistance. We aimed to establish molecular imaging during treatment with sunitinib using the fibronectin extradomain A specific small immunoprotein(SIP)-F8 in glioma. Methods: Biodistribution analysis of F8-SIP-Alexa-555 was performed in SF126-glioma bearing or control mice (n = 23 and 7, respectively). Intravital microscopy(IVM) was performed on a microvascular level after 7 days (n = 5 per group) and subsequently after 6 days of sunitinib treatment (n = 4) or without (n = 2). Additionally, near infrared fluorescence(NIRF) imaging was established with F8-SIP-Alexa-750 allowing non-invasive imaging with and without antiangiogenic treatment in orthotopic tumors (n = 38 divided in 4 groups). MRI was used to determine tumor size and served as a reference for NIRF imaging. Results: F8-SIP demonstrated a time and hemodynamic dependent tumor specific accumulation. A significantly higher vascular accumulation occurred with antiangiogenic treatment compared to untreated tumors enabling visualization of resistant tumor vessels by F8-SIP-mediated NIRF imaging. In orthotopic tumors, sunitinib reduced F8-SIP-Alexa-750 enrichment volume but not fluorescence intensity indicative of F8-SIP accumulation in fewer vessels. Conclusion: F8-SIP is highly tumor specific with time and hemodynamic dependent biodistribution. The higher vascular accumulation to remaining vessels enables molecular imaging and targeting of therapy resistant tumor vessels., Oncotarget, 9 (45), ISSN:1949-2553

Background— It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients. Methods and Results— Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified ( P =0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm 2 versus 4.2±2.1 mm 2 ; P =0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2; P =0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21; P =0.01). Conclusions— CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.

L-Arginine is a precursor of polyamine, nitric oxide (NO), creatine, and agmatine and is essential for the differentiation and proliferation of blood cells, although the precise biological role of L-arginine is unclear. We have recently reported that the depletion of L-arginine in cultured medium prevented both proliferation and differentiation of blood cells (Shima et al., Blood First Edition Paper, October 6, 2005; DOI 10.1182). Since one of metabolic products of L-arginine in the cells is polyamine that associates with cell differentiation and proliferation, the effects of L-arginine on the human K562 cell line and human cord blood-derived CD34 positive cells were investigated by focusing on polyamines such as putrescine, spermidine, and spermine in the present study. When polyamines were added to the culture medium in the absence of L-arginine, the cells did not grow or differentiate well. However, when intracellular polyamines were depleted using ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), the proliferation and differentiation of K562 cells to erythrocytes were reduced even in the presence of L-arginine. Moreover, in the presence of DFMO, cell differentiation and proliferation were recovered by the addition of putrescine or spermidine in the presence of L-arginine. Accordingly, it was demonstrated that polyamines are essential for the proliferation and differentiation of the blood cells as the metabolites of L-arginine and the externally added polyamines are also effective by being taken up through polyamine transporter.

Background: The possibility of eradicating cancer by selective destruction of tumour blood vessels may represent an attractive therapeutic avenue, but most pharmaceutical agents investigated so far did not achieve complete cures and are not completely specific. Antibody conjugates now allow us to evaluate the impact of selective vascular shutdown on tumour viability and to study mechanisms of action. Methods: We synthesised a novel porphyrin-based photosensitiser suitable for conjugation to antibodies and assessed anticancer properties of its conjugate with L19, a clinical-stage human monoclonal antibody specific to the alternatively spliced EDB domain of fibronectin, a marker of tumour angiogenesis. Results: Here we show in two mouse model of cancer (F9 and A431) that L19 is capable of highly selective in vivo localisation around tumour blood vessels and that its conjugate with a photosensitiser allows selective disruption of tumour vasculature upon irradiation, leading to complete and long-lasting cancer eradication. Furthermore, depletion experiments revealed that natural killer cells are essential for the induction of long-lasting complete responses. Conclusions: These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis., British Journal of Cancer, 104 (7), ISSN:0007-0920, ISSN:1532-1827

Purpose This study compared cardiac computed tomography (CT) and two-dimensional transthoracic echocardiography (ECC) for assessing left ventricular ejection fraction (LVEF) using real-world data from a large patient population.

To evaluate the diagnostic accuracy of 64-slice CT coronary angiography (CT-CA) for the detection of significant coronary artery stenosis in patients with zero on the Agatston Calcium Score (CACS). We enrolled 279 consecutive patients (96 male, mean age 48 +/- 12 years) with suspected coronary artery disease. Patients were symptomatic (n = 208) or asymptomatic (n = 71), and underwent conventional coronary angiography (CAG). For CT-CA we administered an IV bolus of 100 ml of iodinated contrast material. CT-CA was compared to CAG using a threshold for significant stenosis of a parts per thousand yen50%. The prevalence of disease demonstrated at CAG was 15% (1.4% in asymptomatic). The population at CAG showed no or non-significant disease in 85% (238/279), single vessel disease in 9% (25/279), and multi-vessel disease in 6% (16/279). Sensitivity, specificity, and positive and negative predictive values of CT-CA vs. CAG on the patient level were 100%, 95%, 76%, and 100% in the overall population and 100%, 100%, 100%, and 100% in asymptomatic patients, respectively. CT-CA proves high diagnostic performance in patients with or without symptoms and with zero CACS. The prevalence of significant disease detected by CT-CA was not negligible in asymptomatic patients. The role of CT-CA in asymptomatic patients remains uncertain.

Purpose. This study aimed to evaluate the diagnostic accuracy of stress electrocardiogram (ECG) and computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis (>= 50%) in the real world using conventional CA as the reference standard. Materials and methods. A total of 236 consecutive patients (159 men, 77 women; mean age 62.8 +/- 10.2 years) at moderate risk and with suspected coronary artery disease (CAD) were enrolled in the study and underwent stress ECG, CTCA and CA. The CTCA scan was performed after i.v. administration of a 100-ml bolus of iodinated contrast material. The stress ECG and CTCA reports were used to evaluate diagnostic accuracy compared with CA in the detection of significant stenosis >= 50%. Results. We excluded 16 patients from the analysis because of the nondiagnostic quality of stress ECG and/or CTCA. The prevalence of disease demonstrated at CA was 62% (n=220), 51% in the population with comparable stress ECG and CTCA (n=147) and 84% in the population with equivocal stress ECG (n=73). Stress ECG was classified as equivocal in 73 cases (33.2%), positive in 69 (31.4%) and negative in 78 (35.5%). In the per-patient analysis, the diagnostic accuracy of stress ECG was sensitivity 47%, specificity 53%, positive predictive value (PPV) 51% and negative predictive value (NPV) 49%. On stress ECG, 40 (27.2%) patients were misclassified as negative, and 34 (23.1%) patients with nonsignificant stenosis were overestimated as positive. The diagnostic accuracy of CTCA was sensitivity 96%, specificity 65%, PPV 74% and NPV 94%. CTCA incorrectly classified three (2%) as negative and 25 (17%) as positive. The difference in diagnostic accuracy between stress ECG and CTCA was significant (p

The aim of the study was to compare the coronary artery calcium score (CACS) and computed tomography coronary angiography (CTCA) for the assessment of non-obstructive/obstructive coronary artery disease (CAD) in high-risk asymptomatic subjects. Two hundred and thirteen consecutive asymptomatic subjects (113 male; mean age 53.6 +/- 12.4 years) with more than one risk factor and an inconclusive or unfeasible non-invasive stress test result underwent CACS and CTCA in an outpatient setting. All patients underwent conventional coronary angiography (CAG). Data from CACS (threshold for positive image: Agatston score 1/100/1,000) and CTCA were compared with CAG regarding the degree of CAD (non-obstructive/obstructive

PURPOSE: This study compared the role of multislice computed tomography coronary angiography (MSCT-CA) and stress electrocardiography (ECG) in the diagnostic workup of patients with chronic chest pain. MATERIALS AND METHODS: MSCT-CA was performed in 43 patients (31 men, 12 women, mean age 58.8+/-7.7 years) with stable angina after a routine diagnostic workup involving stress ECG and conventional CA. The following inclusion criteria were adopted: sinus rhythm and ability to hold breath for 12 s. Beta-blockers were administered in patients with heart rate>or=70 beats/minute. In order to identify or exclude patients with significant stenoses (>or=50% lumen), we determined posttest likelihood ratios of stress test and MSCT-CA separately and of MSCT-CA performed after the stress test. RESULTS: The pretest probability of significant coronary artery disease (CAD) was 74%. Positive and negative likelihood ratios were 2.3 [95% confidence interval (CI) 1.0-5.3] and 0.3 (95% CI: 0.2-0.7) for the stress test and 10.0 (95% CI: 1.8-78.4) and 0.0 (95% CI: 0.0-infinity) for MSCT-CA, respectively. MSCT-CA increased the posttest probability of significant CAD after a negative stress test from 50% to 86% and after a positive stress test from 88% to 100%. MSCT-CA correctly detected all patients without CAD. CONCLUSIONS: Noninvasive MSCT-CA is a potentially useful tool in the diagnostic workup of patients with stable angina owing to its capability to detect or exclude significant CAD.

The antibody-mediated delivery of therapeutic agents to sites of angiogenesis is an attractive strategy for anticancer therapy, but is largely unexplored in hematologic malignancies. In the present study, we show that the extra domain B (EDB) of fibronectin, a marker of angiogenesis, is expressed in B-cell non-Hodgkin lymphoma (NHL) and that the human monoclonal anti-EDB antibody L19 can selectively localize to the lymphoma-associated subendothelial extracellular matrix. In vivo, the preferential accumulation of the antibody at the tumor site was confirmed by quantitative biodistribution analyses with radioiodinated antibody preparations. The fusion protein L19-IL2, which mediates the delivery of interleukin-2 (IL-2) to the neovasculature, displayed a superior antilymphoma activity compared with unconjugated IL-2 in localized and systemic xenograft models of NHL. When coadministered with rituximab, L19-IL2 induced complete remissions of established localized lymphomas and provided long-lasting protection from disseminated lymphoma. The combined use of rituximab and L19-IL2, which dramatically increases the infiltration of immune effector cells in lymphomas, may deserve clinical investigations, facilitated by the fact that L19-IL2 is currently being studied in phase II clinical trials in patients with solid tumors.

The aim of this study was to determine the predictive value of 64-slice computed tomography coronary angiography (CTCA) for major cardiac events in patients with suspected coronary artery disease (CAD). A total of 187 consecutive patients (119 men, age 62.5 +/- 10.5 years) without known heart disease underwent single-source 64-slice CTCA (Somatom Sensation 64, Siemens) for clinical suspicion of CAD. Patients underwent follow-up for the occurrence of cardiac death, nonfatal myocardial infarction, unstable angina and cardiac revascularization. In total, 2,822 coronary segments were assessed. Forty-two segments (1.5%) were not assessable because of insufficient image quality. Overall, CTCA revealed absence of CAD in 65 (34.7%) patients, nonobstructive CAD (coronary plaque a parts per thousand currency sign50%) in 87 (46.5%) patients and obstructive CAD (> 50%) in 35 (18.8%) patients. A total of 20 major cardiac events (3 myocardial infarctions, 16 cardiac revascularizations, 1 unstable angina) occurred during a mean follow-up of 24 months. One noncardiac death occurred. Seventeen events occurred in the group of patients with obstructive CAD and three events occurred in the group of nonobstructive CAD. The event rate was 0% among patients with normal coronary arteries at CTCA. CTCA has a 100% negative predictive value for major cardiac events at 24-month follow-up in patients with normal coronary arteries.

The treatment of coronary artery stenosis has progressively shifted over the past decades, from surgical (coronary artery bypass graft) to percutaneous (percutaneous coronary intervention and stenting). The recent introduction of drug-eluting stents further reduced the occurrence of in-stent restenosis. However, a non-negligible number of patients need imaging/functional tests when symptoms recur. Multi-slice CT coronary angiography (CT-CA) is a clinical reality for the evaluation of coronary artery stenosis but is still being evaluated for the follow-up after coronary stent implantation. Several factors may impair proper depiction of in-stent lumen even with the most recent CT equipment. In highly selected populations, CT-CA may play a clinical role, even though the performance requirements both from the technical standpoint (ie, CT scanner) and from the training (ie, operators’ experience) are still very demanding. In the meantime, CT technology should improve toward higher contrast, spatial, and temporal resolution in order to achieve the imaging performance needed for clinical implementation.

Background— It is known that 9% to 31% of women and 4% to 14% of men with acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at angiography. These patients represent a diagnostic and therapeutic challenge. Multislice computed tomography (CT) can noninvasively identify the presence of coronary plaques even in the absence of significant coronary artery stenosis. This study evaluated the role of 64-slice CT, in comparison with coronary angiography, in detecting and characterizing coronary atherosclerosis in patients with acute myocardial infarction without significant coronary artery stenosis. Methods and Results— Thirty consecutive patients with acute myocardial infarction but without significant coronary stenosis at coronary angiography underwent 64-slice CT. All coronary segments were quantitatively analyzed by means of coronary angiography (CA-QCA) and 64-slice CT (CT-QCA). Forty-seven (10.4%) of the 450 coronary segments were not evaluable by CT. The mean proximal reference diameters at CT-QCA and CA-QCA were, respectively, 2.88�0.75 mm and 2.65�0.9 mm; the overall correlation between CT-QCA and CA-QCA for quantification of reference diameter was r s =0.77; P s =0.11; P =0.03. Overall CT-QCA showed the presence of 50 plaques, of which only 11 were detected by CA-QCA. CT-QCA identified 25 plaques in infarct-related coronary arteries. Positive remodeling was present in 38 of the 50 plaques (76%), with a higher prevalence in the coronary plaques not visualized by CA-QCA (82.1% versus 54.5%). Conclusions— CT-QCA correlates well with CA-QCA in terms of coronary reference diameter analysis, but not stenosis quantification. Multislice CT can detect coronary atherosclerotic plaques in segments of nonstenotic coronary arteries that are underestimated by CA and may have an incremental diagnostic value for the diagnosis of acute myocardial infarction in patients without significant coronary stenosis at CA.

Purpose. This study was undertaken to describe the correlation between the distribution of coronary artery disease (CAD) in a symptomatic population with suspected ischaemic heart disease, cardiovascular risk factors (RF) and clinical presentation. Materials and methods. We studied 163 patients (mean age 65.5 years; 101 men and 62 women) referred for multidetector computed tomography coronary angiography (MDCT-CA) to rule out CAD. The patients had no prior history of revascularisation or myocardial infarction. We analysed how the characteristics of CAD (severity and type of plaque) can change with the increase in RF and how they are related to different clinical presentations. Results. Patients were divided into three groups according to the number of RF: zero or one, two or three, and four or more. The percentage of coronary arteries with no plaque, nonsignificant disease and significant disease was 55%, 41% and 4%, respectively, in patients with zero or one RF; 27%, 51% and 22%, respectively, in patients with two or three RF; and 19%, 38% and 44%, respectively, in patients with four or more RF. Plaque in patients with nonsignificant disease was mixed in 65%, soft in 18% and calcified in 17%. The percentage of coronaries with no plaque in the three RF groups was 50%, 20% and 0% in patients with typical chest pain and 46%, 24% and 12% in those with atypical pain. The percentage of significant disease in patients with typical pain was 0%, 47% and 86% and in those with atypical pain 4%, 20% and 29%. Conclusions. MDCT plays an important role in the identification of CAD in patients with suspected ischaemic heart disease. Severity and type of disease is highly correlated with RF number and assumes different characteristics according to clinical presentation.

The goal of this article is to illustrate the main invasive and noninvasive diagnostic modalities to image the vulnerable coronary plaque, which is responsible for acute coronary syndrome. The main epidemiologic and histological issues are briefly discussed in order to provide an adequate background. Comprehensive coronary atherosclerosis imaging should involve visualization of the entire coronary artery tree and plaque characterization, including three-dimensional morphology, relationship with the lumen, composition, vascular remodelling and presence of inflammation. No single technique provides such a comprehensive description, and no available modality extensively identifies the vulnerable plaque. In particular, we describe multislice computed tomography, which at present seems to be the most promising noninvasive tool for an exhaustive image-based quantification of coronary atherosclerosis.

Objectives This study sought to evaluate the diagnostic accuracy of 64-slice multislice computed tomography (MSCT) coronary angiography in the follow-up of patients with previous coronary stent implantation. Background Recent investigations have shown increased image quality and diagnostic accuracy for noninvasive coronary angiography with 64-slice MSCT as compared with previous-generation MSCT scanners, but data on the evaluation of coronary stents are scarce. Methods In 182 patients (152 [84%] male, ages 58 ± 11 years) with previous stent (≥2.5 mm diameter) implantation (n = 192), 64-slice MSCT angiography using either a Sensation 64 (Siemens, Forchheim, Germany) or Aquilion 64 (Toshiba, Otawara, Japan) was performed. At each center, coronary stents were evaluated by 2 experienced observers and evaluated for the presence of significant (≥50%) in-stent restenosis. Quantitative coronary angiography served as the standard of reference. Results A total of 14 (7.3%) stented segments were excluded because of poor image quality. In the interpretable stents, 20 of the 178 (11.2%) evaluated stents were significantly diseased, of which 19 were correctly detected by 64-slice MSCT. Accordingly, sensitivity, specificity, and positive and negative predictive value to identify in-stent restenosis in interpretable stents were 95.0% (95% confidence interval [CI] 85% to 100%), 93.0% (95% CI 90% to 97%), 63.3% (95% CI 46% to 81%), and 99.3% (95% CI 98% to 100%), respectively. Conclusions In-stent restenosis can be evaluated with 64-slice MSCT with good diagnostic accuracy. In particular, a high negative predictive value of 99% was observed, indicating that 64-slice MSCT may be most valuable as a noninvasive method of excluding in-stent restenosis.

The aim of this study was to assess the feasibility of three-dimensional (3D) reconstructions and quantitative analysis of the volume of each component of the lung with cystic fibrosis (CF).Twenty-two patients with CF (mean age 17+/-8 years) were included in the study. The patients underwent an unenhanced single-slice spiral computed tomography (CT) chest scan with the following parameters: collimation 3 mm, table feed 6 mm x rot(-1), reconstruction interval 1 mm, soft tissue reconstruction kernel. Four image data sets were obtained: native axial slices, cine-mode display, virtual bronchographic volume-rendered images with algorithm for tissue transition display and virtual endoluminal views. The lungs were segmented manually from the hilum to the visceral pleura on the axial images, and the entire lung volume was calculated. A histogram was generated representing the fractional volume of tissues, the density of which was within a preset range. A curve was then obtained from the histogram.Native axial images and cine-mode display allowed complete evaluation of lung volumes. Virtual bronchography allowed a better assessment of the distribution of bronchiectasis. Virtual bronchoscopy was limited by the fact that it visualised only the surface, without differentiating mucus from the bronchial wall. Manual segmentation and generation of density-volume curves required 41+/-7 min for each lung. Three curve patterns were identified depending on disease severity.Volume-density analysis of lungs with CF is feasible. Its main advantage is that image analysis is not analogical, as the assessment is not performed using scoring systems or similar ordinal scales. This technique cannot differentiate acute from chronic findings, and the predictive value of the curve should be assessed.

Purpose. Our aim was to evaluate the diagnostic accuracy of 64- slice computed tomography coronary angiography (MSCT-CA) for detecting significant stenosis (≥50% lumen reduction) in a population of patients at low to intermediate risk. Materials and methods. We studied 72 patients (38 men, 34 women, mean age 53.9±8.0 years) with atypical or typical chest pain and stratified in the low- to intermediate risk category. MSCT-CA (Sensation 64 Cardiac, Siemens, Germany) was performed after IV administration of 100 ml of iodinated contrast material (Iomeprol 400 mgI/ml, Bracco, Italy). Two observers, blinded to the results of conventional coronary angiography (CAG), assessed the MSCT-CA scans in consensus. Diagnostic accuracy for detecting significant stenosis was calculated. Results. CAG demonstrated the absence of significant disease in 70.1% of patients (51/72). No patient was excluded from MSCTCA. There were 37 significant lesions on 1,098 available coronary segments. Sensitivity, specificity and positive and negative predictive value of MSCT-CA for detecting significant coronary artery on a per-segment basis were 100%, 98.6%, 71.2% and 100%, respectively. All patients with at least one significant lesion were correctly identified by MSCT-CA. MSCT-CA scored 15 false positives on a per-segment base, which affected only marginally the per-patient performance (only one false positive). Conclusions. We concluded that 64-slice CT-CA is a diagnostic modality with high sensitivity and negative predictive value in patients at low to intermediate risk.

BACKGROUND: The aim of this study was to investigate reproducibility and accuracy of computer-assisted coronary plaque measurements by multislice computed tomography coronary angiography (QMSCT-CA). METHODS AND RESULTS: Forty-eight patients undergoing MSCT-CA and coronary arteriography for symptomatic coronary artery disease and quantitative intravascular ultrasound (IVUS, QCU) were examined. Two investigators performed the QMSCT-CA twice and a third investigator performed the QCU, all blinded for each other's results. There was no difference found for the matched region of interest (ROI) lengths (QCU 29.4 +/- 13 mm vs. QMSCT-CA 29.6 +/- 13 mm, P = 0.6; total length = 1,400 mm). The comparison of volumetric measurements showed (lumen QCU 267 +/- 139 mm(3) vs. mean QMSCT-CA 177 +/- 91 mm(3), P < 0.001; vessel 454 +/- 194 mm(3) vs. 398 +/- 187 mm(3), P <

PURPOSE: The purpose of this study was to assess the diagnostic accuracy of 64-slice computed tomography (64-CT) coronary angiography in the detection of coronary in-stent restenosis. MATERIALS AND METHODS: Ninety-five patients (72 men and 23 women, mean age 58+/-8 years) with previous percutaneous coronary intervention with stenting and suspected restenosis underwent 64-CT (Sensation 64, Siemens). The mean time between stent deployment and 64-CT was 6.1+/-4.2 months. The scan parameters were: slices 32 x 2, individual detector width 0.6 mm, rotation time 0.33 s, feed 3.84 mm/rotation, 120 kV, 900 mAs. After the intravenous administration of iodinated contrast material (Iomeprol 400 mgI/ml, Iomeron, Bracco) and a bolus chaser (40 ml of saline), the scan was completed in or =50%), or with in-stent occlusion (100%). The consensus reading was compared with conventional coronary angiography. RESULTS: Four patients were excluded because of insufficient image quality. In the remaining 91, we assessed 102 stents (31 RCA; 10 LM; 54 LAD; 7 CX). In 14 (13.7%) stents, in-stent restenosis (n=8) or in-stent occlusion (n=6) was found. Intimal hyperplasia was detected in 11 (10.8%) stents. The sensitivity and negative predictive value of 64-CT for in-stent occlusion were 100% and 100%, respectively, whereas for all stenoses, >50% they were 92.9% and 98.7%, respectively. CONCLUSIONS: We found that 64-CT has a high diagnostic accuracy for the detection of in-stent restenosis in a selected patient population.

The objective of our study was to compare diagnostic performance of visual and quantitative analysis for the characterization of liver tumors insonated at low transmit power after microbubble contrast agent injection.This series comprised 166 liver tumors (1-5 cm in diameter) in 166 patients (99 men, 67 women; mean age +/- SD, 58 +/- 11 years) scanned at low transmit power (mechanical index: 0.1-0.14) after sulfur hexafluoride-filled microbubble injection. Digital cine clips recorded at the arterial phase (10-40 sec after contrast injection) and late phase (100-300 sec) were analyzed to characterize liver tumors as benign or malignant. Visual analysis was performed by three independent blinded reviewers who evaluated enhancement patterns at the arterial phase and subjective tumor conspicuity at the late phase. Quantitative analysis of videotape intensity (VI: gray-scale levels, 0-255) was performed to calculate objective tumor conspicuity at the late phase: (VI(tumor) - VI(liver)) / VI(liver).Characteristic enhancement patterns were observed in malignant tumors (peripheral rimlike) and benign tumors (peripheral nodular or central and spoke-wheel-shaped). Malignant (n = 95) versus benign (n = 71) tumors differed for subjective (median value: -1 vs 1, respectively) and objective conspicuity at the late phase (-0.6 vs 0.15, respectively; p = 0.001, Mann-Whitney U test) due to persistent microbubble uptake in benign tumors. Diagnostic performance of visual (odds ratio: reviewer 1 = 4.28, reviewer 2 = 10.18, reviewer 3 = 9.56) and quantitative (odds ratio: 89.33) analyses differed significantly in the characterization of liver tumors (p = 0.01, chi-square test).Quantitative analysis revealed higher diagnostic performance than visual analysis to characterize liver tumors insonated at low transmit power after microbubble contrast agent injection.

Background Celiac disease is considered to arise from an inappropriate T-cell–mediated immune response against ingested gluten in genetically predisposed people, whereas the T H 2-type lymphocytes are mostly involved in IgE-mediated reactions. The matter of possible coexistence of T H 1- and T H 2-type diseases is still debated. Objective This study was aimed to evaluate the allergy prevalence in a large series of adults with untreated celiac disease and their families at the moment of diagnosis. We also evaluated whether 1 year of gluten-free diet had any effect on allergy prevalence in our cohort. Methods At the moment of celiac disease diagnosis a standardized questionnaire was administered for detailed information on presence and type of any allergy symptoms in 1044 adult patients with celiac disease, 2752 relatives, and 318 spouses. Those reporting any allergy underwent tests with dosage of serum levels of total IgE and search for serum specific IgE with a standard makeup of 20 antigens and PRICK tests in selected individuals. At follow-up visit patients with celiac disease were administered the same allergy questionnaire. Results One hundred seventy-three patients with celiac disease (16.6%), 523 relative (19%), and 43 spouses (13.5%) had at least 1 allergy ( P = not significant). Atopic dermatitis was more frequent in patients with celiac disease (3.8%) and their relatives (2.3%) than in spouses (1.3%). The presence of allergy in general and atopic dermatitis was not affected by presence of overt malabsorption or duration of undiagnosed disease. Follow-up data showed no change in allergy prevalence in the cohort examined. Conclusion Allergy prevalence in a large series of patients with celiac disease is not different from that of their relatives and spouses. However, atopic dermatitis was about 3 times more frequent in patients with celiac disease and 2 times more frequent in their relatives than in spouses. One year of gluten-free diet did not change allergy prevalence in the celiac group under investigation.

We present a case report of a large and deep osteolytic metastasis radiological documented involving the skull in a woman affected by advanced breast cancer during endocrine therapy.