Fractional flow reserve of intermediate lesions on collateral donor coronary arteries after myocardial infarction

Fractional flow reserve (FFR) is the gold standard for the functional assessment of coronary arteries. The aim of this study was to evaluate the relation between angiography, QCA and FFR in borderline lesions on collateral donor coronary arteries. In addition, FFR is compared with the angiographic appearance of collaterals to infarction-related arteries and echocardiographically assessed viability of infarct related the LV wall. In 60 patients with previous IM and occluded IRA, functional assessment of borderline coronary stenosis (30-70% DS) on collaterals donor artery was performed. We have not found statistically significant differences in these parameters between groups with different angiographic appearances of collaterals and different viability of distal myocardium. However, we found higher FFR values in diabetic patients (p=0.018). Higher FFR values in diabetic patients reveal the negative effects of diabetes on collateral growth and myocardial viability

Fractional flow reserve in patients with intermediate values of Duke Treadmill Score and borderline coronary lesions

Despite the wide usage of exercise ECG tests and Duke Treadmill Score (DTS) in clinical practice, no comparison between this scoring system and Fractional Flow Reserve (FFR) has yet been made, particularly in cases of angiographically verified borderline lesions. Thirty patients with single coronary lesions and angiographically assessed borderline stenosis (between 30-70%) and previously calculated intermediate values of DTS between -10 to +4 were examined using FFR. Adequate specificity and sensitivity (0.769 and 0.556, respectively) were in a more narrow range of -0.5 to -10. Sex and age did not have an influence on the DTS values. There was a correlation between the values of FFR and age (r=0.395, p=0.031) and between angiographic assessment of stenosis and quantitative coronary angiography (QCA) (r=0.648, p<0.0001). In the study population, a decision on revascularization could not be based solely on angiographic or QCA assessment of the artery or on the values of DTS

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience

IntroductionPeptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment.MethodologyWe retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups.ResultsA total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p&lt;0.05), functional tumors (p&lt;0.05), absolute neutrophil count (p&lt;0.05), neutrophil-lymphocyte ratio-NLR (p&lt;0.05), C-reactive protein-CRP (p&lt;0.05), CRP/Albumin (p&lt;0.05), alanine aminotransferase-ALT (p&lt;0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p&lt;0.001), age (p&lt;0.05), CRP (p&lt;0.05), and ALT (p&lt;0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively.ConclusionThe study’s results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly

A Novel, “Double-Clamp” Binding Mode for Human Heme Oxygenase-1 Inhibition

The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be ∼15 times more potent (IC50 = 0.27±0.07 µM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC50 = 4.0±1.8 µM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This “double-clamp” binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors

Comparison of Thyroglobulin Concentrations Measured by Two Immunoradiometric Assay

Circulating thyroglobulin measurements is a highly specific test in the management of patients affected by differentiated thyroid cancer after total thyroidectomy, followed by radioiodine ablation. The aim of our study was to compare two thyroglobulinimmunoradiometric assays (INEP, Serbia and Cisbio Bioassays, France). Study included 42 patients of both genders with DTC. The subjects were on suppres¬sive doses of levothyroxine and followed up. Results showed concordance between the two assay methods for determining serum thyroglobulin for 39 (92.85%) patients. Statistical analysis showed that there was a direct correlation between two IRMA tests, with a positive correlation coefficient r=0.613 (p 0.05). We concluded that there is good agreement between the two thyroglobulin assays compared in this study

Clinical Usefulness of 99mTc-HYNIC-TOC and 131I-MIBG Scintigraphy in the Evaluation of Adrenal Tumors

Disorders and morphological abnormalities affecting the adrenal gland, could lead to profound clinical consequences, owing to its biochemical structure-activity and morphological characteristics

Rates of nucleotide substitution, mutation at a locus, and the "beanbag" gene number in man

We estimated the number of different human genes by relating the patterns of spontaneous mutation at the population and individual level. A geometric distribution model of mutation was used in which the average rates of nucleotide replacement (P) and mutation at a locus (p), obtained by experiment, were used to determine the estimate of the physical size of the coding genome (n) in man. The probabilistic relation used, P = (1 - p)(n-1)p, integrates two different referential time scales of mutation, that of a nucleotide and year and that of a coding gene and generation. The estimates of n, for different values of P and p, are compatible with the experimentally determined genome sizes. The size of the coding portion of the genome appears to be evolutionarily constrained by an interplay between the rate of nucleotide replacement and the pattern of mutation at the level of the individual locus. The evolution of the size of the coding genome may be more dependent on the number of generations than on time

Early recurrent left atrial myxoma in a teenager with de novo mutation of Carney complex

We report a case of an extremely early recurrence of left atrial myxoma in a 13-year-old girl. On hospital admission, the clinical presentation was of cerebral embolism with noticeable spotty skin pigmentation and hypertelorism. The left atrial myxoma originated from the roof of the left atrium. The histology specimen showed typical finding of a myxoma. Six months later a new intracardial mass was evacuated, the postoperative result showing the same type of myxomatous tissue. Genetic investigations demonstrated Carney complex. The genetic analysis of the child's family was negative, demonstrating de novo mutation of this rare disorder