Combined imaging with 18F-FDG-PET/CT and 111In-labeled octreotide SPECT for evaluation of thymic epithelial tumors.

PURPOSE: This study aimed to test the role of combined imaging with 18F-FDG-PET/CT and 111In-octreotide SPECT in characterizing thymic epithelial tumors (TETs). METHODS: We evaluated 20 patients with newly diagnosed TETs who had undergone concomitant 18F-FDG-PET/CT and 111In-octreotide SPECT. Thymic epithelial tumors were classified by World Health Organization (WHO) as low-risk thymomas (5), high-risk thymomas (4), and thymic carcinomas (11, among which 6 neuroendocrine tumors). Patients were staged according to Masaoka system. 18F-FDG-PET/CT was performed and SUV(max) of primary tumors was recorded. 111In-octreotide SPECT of the thorax was performed, and tumor-to-background ratio was determined on the 24-hour coronal sections. RESULTS: All patients showed increased 18F-FDG uptake in mediastinal lesions. SUV(max) were significantly correlated with WHO classification (r = 0.66, P < 0.01) and with Masaoka stage (r = 0.60, P < 0.01). SUV(max) of low-risk thymomas (mean [SD], 2.87 [0.83]) were significantly lower than those of high-risk thymomas (mean [SD], 7.21 [1.73], P < 0.01) and of thymic carcinomas (mean [SD], 9.39 [5.80], P < 0.05), whereas no significant difference was found between high-risk thymomas and thymic carcinomas. SUV(max) of all high-risk thymomas and thymic carcinomas was 4.5 or greater. All primary tumors were detected by In-octreotide SPECT, and tumor-to-background ratios ranged between 1.67 and 10.10. No statistically significant correlation was found between tumor-to-background ratios and WHO classification (r = 0.24, P = 0.36) and Masaoka stages (r = 0.31, P = 0.23). However tumor-to-background ratios of thymic neuroendocrine tumors (mean [SD], 5.71 [3.09]) were significantly higher than those of all other TETs with SUV(max) of 4.5 or greater (mean [SD], 2.41 [0.56]; P < 0.05). CONCLUSIONS: 18F-FDG-PET/CT scan allows to differentiate high-risk epithelial tumors and thymic carcinomas from low-risk thymomas, whereas 111In-octreotide SPECT may identify neuroendocrine tumors among those showing high 18F-FDG uptake.

Incremental prognostic value of stress myocardial perfusion imaging in asymptomatic diabetic patients.

OBJECTIVE: Stress myocardial perfusion single-photon emission computed tomography (MPS) variables are robust estimators of prognosis. No data are available on the comparative ability of stress MPS risk markers using varied iterative and risk classification approaches in asymptomatic diabetic patients. We compared analytical approaches to estimate the added value of MPS variables in estimating coronary artery disease (CAD) outcomes in asymptomatic diabetic patients. We also evaluated the temporal characteristics of cardiac risk according to MPS findings. METHODS: A total of 436 consecutive asymptomatic diabetic patients who underwent stress-rest gated MPS were prospectively enrolled. Multivariable Cox proportional hazards model was employed to estimate cardiac death and nonfatal myocardial infarction (MI). Risk reclassification was calculated and parametric survival analysis was used to predict time to events. RESULTS: At multivariable analysis, post-stress left ventricular ejection fraction (LVEF) and stress MPS ischemia were independent predictors of CAD death or MI (both p < 0.01). The net reclassification improvement by adding MPS results to a model including pre-test CAD likelihood was 0.25 (95% confidence interval 0.06-0.44; p < 0.01). Parametric survival analysis showed the highest probability of CAD death or MI and the major risk acceleration in time in patients with stress MPS ischemia and post-stress LVEF ≤45%. CONCLUSION: In asymptomatic diabetic patients, analytical approaches that establish the reclassification of events may serve for estimation of improved outcomes for stress MPS. Post-stress LVEF and stress-induced ischemia by gated MPS influence the temporal characteristic of the patient's risk at long-term follow-up.

Exercise training early after acute myocardial infarction reduces stress-induced hypoperfusion and improves left ventricular function.

PURPOSE: Exercise training might exert its beneficial effects on myocardial perfusion by inducing coronary vascular adaptations or enhancing collateralization. We evaluated whether long-term exercise-based cardiac rehabilitation started early after ST-elevation acute myocardial infarction (STEMI) improves myocardial perfusion and left ventricular (LV) function. METHODS: Forty-six patients with recent STEMI and residual inducible hypoperfusion were randomized into two groups: 25 enrolled in a 6-month outpatient exercise-based cardiac rehabilitation programme (group T) and 21 discharged with generic instructions for maintaining physical activity and correct lifestyle (group C). All patients underwent cardiopulmonary exercise test and dipyridamole rest gated myocardial perfusion single photon emission computed tomography within 1 week after STEMI and at 6-month follow-up. RESULTS: At follow-up, group T showed an improvement in peak oxygen consumption, oxygen pulse and in the slope of increase in ventilation over carbon dioxide output (all p < 0.01) associated with a reduction of stress-induced hypoperfusion (p < 0.01) and an improvement in resting and post-stress wall motion score indexes (both p < 0.01), resting and post-stress wall thickening score indexes (both p < 0.05) and resting and post-stress LV ejection fraction (both p < 0.05). On the contrary, no changes in cardiopulmonary indexes, myocardial perfusion and LV function parameters were observed in group C at follow-up. CONCLUSION: Exercise training started early after STEMI reduces stress-induced hypoperfusion and improves LV function and contractility. Exercise-induced changes in myocardial perfusion and function were associated with the absence of unfavourable LV remodelling and with an improvement of cardiovascular functional capacity.

Prognostic value of coronary artery calcium score and coronary CT angiography in patients with intermediate risk of coronary artery disease.

The aim of this study was to compare the prognostic value of coronary calcium scoring and coronary computed tomography (CT) angiography in assessing the cardiac risk and its temporal characteristics in patients at intermediate pre-test likelihood of coronary artery disease (CAD). Cardiac CT was performed in 326 patients at intermediate (15-85%) pre-test likelihood of CAD to evaluate calcium score and presence and severity of the disease. Patients were followed-up for the occurrence of major cardiac events (cardiac death, myocardial infarction, and unstable angina requiring revascularization). During follow-up (26 ± 12 months) 34 events occurred. Calcium score, extent of CAD, and plaque extent and distribution were higher (all P < 0.001) in patients with events than in those without. No patients with calcium score of 0 had events at follow-up. Calcium score (P < 0.001), number of segments with non-calcified or mixed plaque (P < 0.05), and segments-at-risk-score (P < 0.005) were independent predictors of events. Cardiac risk was greater for all time intervals and accelerated more over time with worsening of calcium score. In presence of coronary calcium, significant CAD further increased the probability of failure for all time intervals. Therefore, patients at intermediate CAD risk without coronary calcium do not need further evaluation with longer and higher-radiation-dose protocols, while in the presence of coronary calcium CT angiography is useful to further stratify patients.

A novel NKX2.1 mutation in a family with hypothyroidism and benign hereditary chorea.

BACKGROUND: We studied a boy with congenital hypothyroidism, benign hereditary chorea, and respiratory distress. His mother and his grandfather were affected by hypothyroidism with a late onset and benign hereditary chorea. The aim of this study was to establish the genetic defects that cause that phenotype and study the molecular mechanisms of the pathology. METHODS: NKX2.1, PAX8, NKX2.5, and TAZ genes were sequenced. RESULTS: Direct sequencing of the NKX2.1 gene showed, in all the affected, a new heterozygous mutation from cytosine to adenine in the second base of the triplet encoding for the amino acid at position 145. The mutation (C609A) is responsible for a change from serine to a stop codon (S145X). We also demonstrated that the mutant protein is predominantly in the cytoplasm and unable to translocate into the nucleus. Of note, the S145X mutation produces variable phenotypes in the affected members of the family. No mutations have been identified in the NKX2.5, PAX8, and TAZ genes. CONCLUSIONS: Our study extends the knowledge of the functional effect of NKX2.1 mutations and further highlights the complexities of genotype-phenotype correlation in the NKX2.1 deficiency syndromes.

A new case of familial nonautoimmune hyperthyroidism caused by the M463V mutation in the TSH receptor with anticipation of the disease across generations: a possible role of iodine supplementation.

OBJECTIVE: Hereditary (familial) nonautoimmune hyperthyroidism (FNAH) is caused by activating thyroid-stimulating hormone (thyrotropin) receptor (TSHR) germline mutations. We describe a family with recurrent thyrotoxicosis and goiter across three generations, including an 8-year-old girl. MAIN OUTCOME: Sequences of the TSHR gene in the index patient, her father, her paternal grandmother, and a paternal uncle demonstrated the presence of an identical germline TSHR mutation. The mutation was heterozygous and determined the substitution of valine for methionine (codon 463; ATG-->GTG) in the second transmembrane domain of the TSHR in all the affected patients, but in none of the unaffected family members. CONCLUSIONS: We compared the clinical presentation of FNAH in the family reported by us with the other cases harboring the same mutation reported in the literature. This analysis revealed high variability in the phenotypical expression of the disease. In the family reported by us, we also observed a clear anticipation of the onset of the disease across generations, and we discussed whether such a phenomenon can be the consequence of the increased iodine supplementation in the area where the family lives.