To investigate the role of intracoronary pressure parameters in the assessment of viability in the myocardium subtending a significant coronary stenosis. In patients with ischemic left ventricular dysfunction, the presence of myocardial viability is related to the expected benefits derived from coronary revascularization. Intracoronary pressure wire-based measurements were performed in 64 coronary lesions of ≥50% stenosis severity of 59 patients with postischemic left ventricular dysfunction, segmental left ventricular wall motion abnormalities, and substantial viability in the myocardial territory subtending the investigated stenotic coronaries, defined as the percent summed rest score in the target territory (%SRStarget ) ≤60% at the single-photon emission tomography. Invasive pressure-derived indexes like resting and hyperemic Pd/Pa, ΔPd/Pa, and %ΔPd/Pa (defined as the absolute difference and percent decrease between resting and hyperemic Pd/Pa respectively) were compared with %SRStarget . A significant correlation was found between ΔPd/Pa (Spearman's p: -0.760, p < 0.001) and %ΔPd/Pa (p: -0.733; p < 0.001) with %SRStarget. These results were confirmed after correction for potential confounders. According to %SRStarget median value, myocardial areas with high and low viability were compared: ΔPd/Pa and %ΔPd/Pa were significantly higher in areas with high viability (p < 0.001 for both). According to receiver operating characteristic curves, we identified two cut-offs (ΔPd/Pa > 0.11 and %ΔPd/Pa > 15%) able to predict >80% viability with good sensitivity and specificity. Our study suggests that, in patients with postischemic left ventricular dysfunction and significant coronary stenosis, intracoronary pressures indexes like ΔPd/Pa and %ΔPd/Pa are able to predict the magnitude of downstream myocardial viability.

OBJECTIVES The ventrodorsal hip extended standard view is conventionally used for radiographic screening of canine hip dysplasia. However, because the ventrodorsal hip extended standard view minimises hip joint laxity, several alternative views have been proposed. Our aim was to evaluate a new ventrodorsal hip flexed and not distracted view to assess joint laxity, by comparing it with the ventrodorsal hip extended standard and ventrodorsal hip flexed and distracted views. MATERIALS AND METHODS Between April 2013 and March 2017, all dogs referred to the University of Naples "Federico II" for the diagnosis of canine hip dysplasia were studied using the ventrodorsal hip extended standard, ventrodorsal hip flexed and not distracted and ventrodorsal hip flexed and distracted views. The Norberg angle and the laxity index were measured for each view. RESULTS Overall, 102 dogs, 67 males and 35 females, mean age 15 months, were included. The mean (±standard deviation) Norberg angles were 99.77° (±10.42°), 89.29° (±14.32°) and 91.80° (±13.50°) for the ventrodorsal hip extended standard, ventrodorsal hip flexed and not distracted and ventrodorsal hip flexed and distracted views, respectively. The mean (± standard deviation) laxity indices were 0.19 (± 0.14), 0.39 (± 0.25) and 0.36 (± 0.21), respectively. The ventrodorsal hip flexed and distracted and ventrodorsal hip flexed and not distracted views had lower Norberg angle and higher laxity index values compared with the ventrodorsal hip extended standard view. The ventrodorsal hip flexed and distracted and ventrodorsal hip extended standard views are in strong agreement for the measurement of both Norberg angle and laxity index, as confirmed by Bland-Altman analysis and the intraclass correlation coefficient. CLINICAL SIGNIFICANCE The ventrodorsal hip flexed and distracted and ventrodorsal hip flexed and not distracted views obtained with the hip in a neutral position reveal joint laxity better than the ventrodorsal hip extended standard view. Unlike the ventrodorsal hip flexed and distracted view, the ventrodorsal hip flexed and not distracted view does not require human operators or special devices for positioning the dog. The wide age range of the dogs enrolled might have influenced the laxity index measurements, since capsular fibrosis in older dogs reduces laxity.

BACKGROUND:Congenital erythropoietic porphyria (CEP) is a rare autosomal recessively inherited disorder with chronic and relatively stable presentation. Till now brain blood flow derangements have been described only in acute hepatic porphyrias. We describe the first findings of brain perfusion defects, studied by single photon emission tomography/computed tomography (SPET/CT), in two patients affected by CEP, by using a semi-quantification anatomic-standardized voxel-based program compared with magnetic resonance imaging (MRI) results.SUBJECTS AND METHODS:Two Pakistanis brothers were investigated for CEP confirmed by a genetic test. The disease was severe with: skin burning, mood depression and haemolytic anemia. Considering depression, patients underwent brain SPET/CT and MRI. Single photon emission tomography/CT images were processed by neurostat semi-quantitative software. Data obtained were compared to a normal database and z-score images were generated.RESULTS:In both patients we found several perfusion defects evident in transaxial slices and in z-score images obtained by neurostat processing. Magnetic resonance imaging was negative in both patients. Biochemical mechanisms inducing localized brain hypoperfusion are uncertain. However, mismatch between SPET/CT data and MRI was probably due to absence of necrosis.CONCLUSION:In our opinion, SPET/CT could have a key role in this setting of patients due to its high sensitivity and reliability in mild-to-moderate brain perfusion defects detection. Moreover, the quantitative analysis by using neurostat may allow to recognize even mild brain perfusion alterations, difficult to detect only visually.

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BACKGROUND:Hereditary Coproporphyria (HCP) is characterized by abdominal pain, neurologic symptoms and psychiatric disorders, even if it might remain asymptomatic. The pathophysiology of both neurologic and psychiatric symptoms is not fully understood. Therefore, aiming to evaluate a possible role of brain blood flow disorders, we have retrospectively investigated cerebral perfusion patterns in Single Photon Emission Computed Tomography (SPECT) studies in HCP patients.MATERIALS & METHODS:We retrospectively evaluated the medical records of patients diagnosed as being affected by HCP. A total of seven HCP patients had been submitted to brain perfusion SPECT study with 99mTc-Exametazime (hexamethylpropyleneamine oxime, HMPAO) or with its functionally equivalent 99mTc-Bicisate (ECD or Neurolite) according with common procedures. In 3 patients the scintigraphic study had been repeated for a second time after the first evaluation at 3, 10 and 20 months, respectively. All the studied subjects had been also submitted to an electromyographic and a Magnetic Resonance Imaging (MRI) study of the brain.RESULTS:Mild to moderate perfusion defects were detected in temporal lobes (all 7 patients), frontal lobes (6 patients) and parietal lobes (4 patients). Occipital lobe, basal ganglia and cerebellar involvement were never observed. In the three subjects in which SPECT study was repeated, some recovery of hypo-perfused areas and appearance of new perfusion defects in other brain regions have been found. In all patients electromyography resulted normal and MRI detected few unspecific gliotic lesions only in one patient. Discussion & Conclusions: Since perfusion abnormalities were usually mild to moderate, this can probably explain the normal pattern observed at MRI studies. Compared to MRI, SPECT with 99mTc showed higher sensitivity in HCP patients. Changes observed in HCP patients who had more than one study suggest that transient perfusion defects might be due to a brain artery spasm possibly leading to psychiatric and neurologic symptomatology, as already observed in patients affected by acute intermittent porphyria. This observation, if confirmed by other well designed studies aiming to demonstrate a direct link between artery spasm, perfusion defects and related symptoms could lead to improvements in HCP treatments.

131 Iodine is used both to ablate any residual thyroid tissue or metastatic disease and to obtain whole-body diagnostic images after total thyroidectomy for differentiated thyroid cancer (DTC). Even though whole-body scan is highly accurate in showing thyroid residues as well as metastases of DTC, false positive results can be found, possibly leading to diagnostic errors and unnecessary treatments. This paper reviews the physiological and pathological processes involved as well as the strategy to recognize and rule out false positive radioiodine images.

Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ.Materials and Methods. In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ.Results. Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11.Conclusions. The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis.

sed from 97 + 37 ml/m2 and 126 + 38 ml/m2 to 61 + 34 ml/m2 and 93 + 37 ml/m2 respectively, but did not significantly reduced nor iESV neither iEDV in non responders that passed from 158 + 44 ml/m2 and 196 + 43 ml/m2 to 152 + 45 ml/m2 and to 184 + 44 ml/m2 respectively [3]. In responders the favourable effects of CRT are obtained within 2 months and are stable at least over a period of 6 months [8], but, possibly far longer. Consequently the determinants of CRT outcome are also the determinants of a further clinical course. In subjects with moderate left ventricular enlargement (iEDV 142 ml/m2) no significant functional improvements are obtained by CRT with consequent poor prognosis [6]. In our series all the patients that developed hard events (death or acute heart failure requiring hospitalization) over a two year follow-up had a pre-CRT LVEF no higher than 0.21 with no significant changes after CRT. In a three year survival study [6] on a relatively small series of patients (mean age 74 years) we observed that the subjects died for a worsening heart failure, had pre-CRT iESV volumes > 194 ml/m2. A very important left ventricular enlargement probably accounts for the nearly 30% of patients that do not take advantage from CRT [1, 7]. In the consideration that CRT is usually effective only in subjects with a moderate left ventricular enlargement and without an extremely depressed LVEF, we

# 16 Anomalous origin of the coronary artery – 2 case reports {#article-title-2} An anomalous aortic origin of the coronary artery is rare with a reported incidence of 0.3–1.3 %. Anomalous left coronary artery from the right sinus with an interarterial course has a prevalence of 0.17 % and is associated with a high risk of sudden cardiac death during or after strenuous exertion. The authors report the case of two patients with anomalous origin of the coronary arteries. The first case was a 45-year-old- female patient, with no relevant medical history, referred for cardiology consultation by tachycardia, she reported no other relevant cardiovascular symptoms. After a treadmill exercise test which was electrically positive for ischemia, a cardiac CT was requested to rule out coronary artery disease. Cardiac CT revealed an anomalous origin of the left coronary artery from the right sinus of Valsalva with interarterial course between aorta and pulmonary artery. Second case was a 50-year-old male patient with history of smoking, referred for cardiology consultation by atypical chest pain. A Cardiac TC was requested and revealed anomalous origin of the right coronary above the sino-tubular junction, in the anterior wall of the ascending aorta with initial interartrial course between the great vessels. He also did a SPECT which was negative for ischemia. Both patients were presented to our referral center for Cardiac Surgery to discuss the possibility for surgical coronary revascularization. The authors wish to emphasize that Cardiac TC may be a useful and non-invasive tool to establish diagnosis and a surgical approach to rectify congenital coronary artery anomalies. # 17 123 I-MIBG (123 I-metaiodobenzylguanidine) scintigraphy in myocardial noncompaction {#article-title-3} Background and Aim: Isolated ventricular non-compaction (IVNC) is a rare condition caused by the arrest of myocardial compaction during embryogenesis resulting in multiple, deep, intertrabecular recesses communicating with ventricular cavity. Echocardiography shows a thin, outer (subepicardial) myocardial layer and a very thickened inner spongy zone on the endocardial side with deep recesses communicating with the ventricular cavity and filled with blood. IVNC is associated to a high risk of ventricular arrhythmias and sudden cardiac death (SCD), heart failure and systemic embolization. Patient and Methods: A 51 y old black male with familial history of SCD and with an already known condition of IVNC was admitted to our hospital for a heart evaluation including a 123 I-MIBG myocardial scintigraphy, that is regarded as an effective, safe and reliable method to evaluate the sympathetic innervation of the heart, and consequently, to assess the severity of heart failure. Scintigraphy was performed by i.v. injection of 320 MBq of the noradrenaline analogue 123 I-MIBG. Chest scans at 15 minutes and 4 hours from injection were performed. Regions of interest were drown on the heart (H) and mediastinum (M) and the H/M ratio, normalized per pixel, was than calculated together with the wash-out rate of 123 I-MIBG from myocardium. Results: As 123 I-MIBG demonstrated a significant reduction of the left ventricular sympathetic innervation with H/M ratio of 1.53 and 1.56 at respectively 15 min and 4 h and an increased wash out rate (31%) including decay correction. An ICD (Implantable Cardioverter Defibrillator) was implanted despite a not severely compromised left ventricular ejection fraction (LVEF) at echocardiography (42%). One week later the scintigraphic study the patient suffered a ventricular fibrillation interrupted by ICD discharge. Conclusions: The detection of sympathetic disorder at 123-I MIBG study resulted critical in the decision of implanting an ICD with life-saving demonstrated effect. 123 I-MIBG studies appear therefore especially useful in subjects with moderate LVEF reduction in which this test offers important insights on risk stratification and outcome. As suggested by the increase of 123 I-MIBG wash out and by the decrease of its uptake, a sympathetic heart innervation disorder seems to be associated to IVNC. The high frequency of malignant ventricular arrhythmias found in subjects with IVNC might therefore be partly consequent to reduced sympathetic innervation enhancing reentry phenomena due to anatomical abnormalities and to ischemic scarring. # 18 Incidental detection of a paracardiac aortic paraganglioma via coronary angiography and cardiac CT : Hybrid revascularisation of the patient {#article-title-4} Incidental detection of a paracardiac aortic paraganglioma via coronary angiography in a patient with a thrombotic coronary arterial occlusion. 55 year old man managed during acute myocardial infarction and incidentally paracardiac mass was seen via coronary angiography. Then transesophageal echocardiography showed the mass and multislice CT scan confirmed the mass at posterior of the ascendan aorta. For thrombotic occlusion balloon angioplasty performed but stent was not deployed. He referred to surgery and mass mass excised with a two vessel coronary bypass graft. Paracardiac masses are very rare entities and paragangliomas are extremely rare. When a paracaridac mass detected, approach must be individualised and different imaging modalities should be used for precise diagnose before complete revascularisation. # 20 Recurrent ventricular arrhythmias in a patient with cardiac sarcoid {#article-title-5} A 60 year old woman was referred for management of non sustained broad complex tachycardia with trifasicular block and intermittent complete heart block. The echocardiogram showed septal thickening with normal LV function. The presentation was suggestive of cardiac sarcoid. She was unable to tolerate the planned cardiac MRI due to claustrophobia. A thoracic and abdominal CT was therefore performed and again this showed no evidence of lymphadenopathy or sarcoid. Whilst the CT was principally aimed at excluding extra cardiac sarcoid the CT did show an interventricular septal nodule. A dual chamber ICD was implanted. She was subsequently admitted with recurrent appropriate ICD shocks and incessant VT. Echocardiography demonstrated severe LV impairment with marked dysschrony. This was thought to be due to tachycardia mediated cardiomyopathy, high percentage of RV pacing and possible disease progression. The device was upgraded to a CRT-D with implantation of an LV lead. An RV septal biopsy confirmed cardiac sarcoid and prednisolone was started. She developed a cushingoid appearance but was continued on high dose therapy due to the burden of ventricular arrhythmias. Methotrexate was subsequently introduced as a steroid sparing agent. This was later reduced due to a deterioration in her liver enzymes and the prednisolone increased. During follow up there was a significant increase in her arrhythmia burden with recurrent VT and multiple ICD shocks. This was thought to be due to sarcoid disease progression, either as a manifestation of myocardial scarring or sarcoidosis related inflammation. If sarcoid inflammation was present more aggressive immunosuppressive therapy regime would be required. The patient was limited by proximal myopathy secondary to steroid therapy and it was important to clarify the need for further immunosupression. A tetrofosmin myocardial perfusion scan and fasting FDG PET CT scan was performed to clarify if there was any active cardiac disease. The resting myocardial perfusion images showed almost absent uptake of the tracer in the infero septal region of the myocardium extending into the anterior septum and inferior wall with normal uptake elsewhere. There was almost full thickness myocardial damage in the septum and part of the inferior wall. There was no increase in FDG uptake in this region suggesting burnt out disease. The PET study was critical in establishing that there was no on-going active inflammatory cardiac sarcoid. This allowed the steroids to be weaned giving a significant improvement in the patient's muscle weakness and quality of life. # 21 An unusual cause for collapse {#article-title-6} A 25-year-old Nigerian gentleman presenting with collapse upon exertion; he had no relevant cardiac history but two similar episodes previously. Electrocardiography on admission showed sinus rhythm with tall R waves in the precordial leads, fixed early depolarisation in the anterior leads and T wave inversion in the lateral leads, associated with a raised troponin I. Coronary angiography showed an aberrant right coronary artery arising form the left coronary sinus. This was confirmed on cardiac MRI showing the course of the right coronary artery had an anomalous origin from the left coronary sinus and crossed anteriorly to the aorta and behind the pulmonary artery. Anomalous coronary anatomy has been associated with angina, myocardial infarction and sudden cardiac death; they are the second most common cause of sudden cardiac death in young athletes after hypertrophic cardiomyopathy. These anomalies can be investigated with MRI or CT, with CT coronary angiography being the current gold standard investigation. Management options include conservative therapy with beta-blockers, angioplasty or surgery. Patients who are symptomatic are generally offered surgical intervention, however management of asymptomatic patients is less certain.

The high malignancy of glioblastoma has been recently attributed to the presence, within the tumor, of glioblastoma stem cells (GSC) poorly responsive to chemo- and radiotherapy. Here, the potential employment of metformin and arsenic trioxide (ATO) in glioblastoma therapy is discussed focusing on their effects on GSC. Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells. Metformin and ATO induce autophagy and apoptosis in glioma cells by inhibiting and stimulating the PI3K/Akt and the mitogen-activated protein kinase pathways, respectively. Both drugs promote differentiation of GSC into non-tumorigenic cells. In this regard, metformin acts via activation of the AMPK-FOXO3 axis, whereas ATO blocks the interleukin 6-induced promotion of STAT3 phosphorylation. Blood-brain barrier, easily crossed by metformin but not by ATO, undergoes important glioblastoma-induced alterations that increase its permeability, thus allowing ATO to distribute more into the glioblastoma bulk than in the normal brain parenchyma. A prompt clinical assessment of metformin and ATO in glioblastoma patients would represent a valid attempt to improve their survival.

Hyperhomocysteinemia is a widely recognized, although not yet entirely understood, risk factor for cardiovascular disease. Particularly, the complex relationships between age, hyperhomocysteinemia, predisposing genetic factors and peripheral vascular diseases have not been fully evaluated. Our contribution to this issue is a retrospective analysis of a large series of patients with peripheral arterial, venous and lymphatic disease, and of their blood relatives, with special reference to homocysteine plasma levels, age and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Serum homocysteine was measured in 477 patients (286 males, 191 females, age range 19-78 years) with various vascular clinical conditions: postphlebitic syndrome (46) recurrent venous ulcers (78), arterial diseases (101) primary lymphoedema (87), secondary lymphoedema (161) and outlet thoracic syndrome (4), and in 50 normal controls. A MTHFR study for polymorphisms was carried on in the subjects with homocysteine values exceeding 15 mol/L. Serum homocysteine determination and MTHFR polymorphism studies were performed also in 1430 healthy blood related relatives (mainly siblings, descendents and sibling descendents) of the subjects with hyperhomocysteinemia and MTHFR polymorphisms. We found MTHFR polymorphisms in 20% of controls and in 69.3%, 69.5% and 53.8% of hyperhomocysteinemic subjects with arterial diseases, postphlebitic syndrome and venous ulcers, respectively. As expected, the percentage of hyperhomocysteinemia in patients with secondary lymphoedema and with thoracic outlet syndrome did not show significant differences compared to the control group. A MTHFR polymorphism was found in 116 out of the 214 hyperhomocysteinemic patients, i.e., in the 54% of the overall patient population with hyperhomocysteinemia (214 patients). Interestingly 750 (52%) out of the 1430 blood relatives of the 116 patients with hyperhomocysteinemia and MTHFR polymorphisms showed at least one polymorphism in MTHFR gene. In this latter group of 750 healthy blood-related relatives bearing a MTHFR polymorphism the finding of hyperhomocysteinemia increased according to the age class from 1.6% in the age range <40 years up to 54.9% in the age range >60 years. The present study demonstrate that patients with peripheral arterial disease, post-phlebitic syndrome, venous ulcers and primary lymphoedema show a significantly higher incidence of hyperhomocysteinemia compared to controls, and adds further evidence to the causative role of hyperhomocysteinemia in the development of both arterial and venous disease. Moreover our data indicate a possible causative role of hyperhomocysteinemia in primary lymphoedema. In more than 50% of our hyperhomocysteinemic patients a polymorphism of MTHFR (C677T and/or A1298C) was detected. In subjects with these polymorphisms the frequency of hyperhomocysteinemia increases with age. We observed a quite similar frequency of the two polymorphisms in the studied population and therefore claim for the need to study both C677T and A1298C mutations in hyperhomocysteinemic patients.

Section of Pharmacology and Toxicology Department of Basic and Applied Biology University of L'Aquila L'Aquila, Italy (Carmignani) Department of Nuclear Medicine Scientific Institute ‘Casa Sollievo della Sofferenza’ San Giovanni Rotondo, Italy (Valle) Section of Pharmacology and Toxicology Department of Basic and Applied Biology University of L'Aquila L'Aquila, Italy (Volpe) * See also p. 842. The authors have not disclosed any potential conflicts of interest.

Facciorusso, Antonio; Stanislao, Mario; Fanelli, Mario; Valori, Vanna M; Valle, Guido Author Information