Influence of characteristics of epicardial adipose tissue and myocardial sympathetic innervation on the development of late recurrence of atrial fibrillation after radiofrequency ablation

Aim. To investigate the relationship between radiological characteristics of epicardial adipose tissue (EAT) and myocardial sympathetic activity, as well as to study their association with late recurrence of atrial fibrillation (AF) after radiofrequency ablation (RFA).Material and methods. This prospective study included 26 people with persistent and long-standing persistent AF scheduled for interventional AF treatment. Before the RFA procedure, all patients underwent cardiac 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy to assess the myocardial sympathetic innervation and contrast-enhanced cardiac multislice computed tomography to assess pulmonary vein anatomy, left atrial volume, and EAT volume. Clinical follow-up, including 12-lead electrocardiography (ECG) and 24-hour ECG monitoring, was carried out 3, 6 and 12 months after RFA.Results. After the end of follow-up, the patients were divided into two groups: with AF recurrence (group 1, n=8) and without AF recurrence (group 2, n=18). Multivariate logistic analysis found that only the 123I-MIBG washout rate (odds ratio, 1,0943; 95% confidence interval, 1,0138-1,1812) proved to be an independent predictor of late AF recurrence after RFA. ROC analysis revealed that a 123I-MIBG washout rate >21% with a sensitivity of 75% and a specificity of 83,3% (AUC=0,844; p<0,001) predicts late AF recurrence after RFA.Conclusion. Parameters of myocardial sympathetic activity, assessed by 123I-MIBG myocardial scintigraphy, are associated with late AF recurrence after RFA in patients with persistent and long-standing persistent AF. There were no reliable data confirming associations between myocardial sympathetic innervation and radiological EAT indicators, as well as the effect of the latter on the risk of AF recurrence after RFA.

Preparation and Characterization of Moldable Demineralized Bone Matrix/Calcium Sulfate Composite Bone Graft Materials

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO4, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and β-form of calcium sulfate hemihydrate (CaSO4 •0.5H2O, CSH) were produced by heating gypsum (CaSO4 •2H2O). The morphology and particle sizes of α- and β-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or β-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler.

Administration of a VEGFR‑2-specific MRI contrast agent to assess orthodontic tooth movement

Purpose It is thought that orthodontic forces initially reduce periodontal blood flow during orthodontic tooth movement (OTM) via tissue compression with cells responding to concomitant oxygen deprivation with expression of vascular endothelial growth factor (VEGF) triggering angiogenesis via binding to its receptor VEGFR‑2. To test this hypothesis, we performed a pilot study to establish a protocol for molecular magnetic resonance imaging (MRI) of rat jaws administering a VEGFR-2-specific contrast agent. Methods Mesial OTM of a first upper left rat molar was initiated in one male Fischer 344 rat 4 days prior to MRI by insertion of an elastic band between the first and second upper molars with the contralateral side left untreated (internal control). T1-weighted MRI sequences including dynamic contrast-enhanced MRI (DCE-MRI) were recorded before and after administration of a molecular VEGFR‑2 MRI marker with a 7 T MRI dedicated for small animal use. Results After injection of anti-VEGFR2-albumin-gadolinium-DTPA, volume enhancement on T1-weighted images was increased at the OTM side distally of the moved first upper molar (M1) compared to the control side, whereas the T1 relaxation time was reduced on the OTM side. DCE-MRI resulted in an increased area under the curve (AUC), whereas time-to-peak (TTP) and washout rate were reduced during OTM distally of the moved M1 compared to the contralateral side. Conclusions OTM resulted in uptake of the VEGFR-2-specific MRI contrast agent in tension areas of the periodontal ligament. The imaging protocol presented here is useful for the assessment of VEGFR‑2 expression in tension areas of the periodontal ligament in vivo.

The clinical value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) semi-quantitative parameters in monitoring neoadjuvant chemotherapy response of osteosarcoma

Background Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive technique which could monitor tumor morphology, blood vessel dynamics, and micro-environmental changes. Purpose To evaluate the value of DCE-MRI semi-quantitative parameters in monitoring the neoadjuvant chemotherapy (NAC) response of osteosarcoma. Material and Methods Twenty-five patients pathologically confirmed as osteosarcoma received four cycles of NAC followed by surgery. All patients underwent conventional and dynamic MRI twice, before starting chemotherapy and before surgical treatment. With a reference standard of histological response (tumor necrosis rate), semi-quantitative parameters were compared between good response group (TNR ≥ 90%) and non-response group (TNR < 90%). The differences between intra- and inter-group parameters before and after NAC were analyzed by Mann–Whitney U test. Receiver operating characteristic (ROC) analysis was generated to assess the parameters’ efficacy in predicting the outcome of NAC. Results The changes were statistically significant on slope, maximum signal intensity (SImax), time to peak (TTP), signal enhanced extent (SEE), peak percent enhancement (PPE), washout rate (WOR), and enhancement rate (ER) in the good response group ( P < 0.05), while only SImax and SEE were different in the non-response group after NAC. The changes in Slope, SImax, TTP, SEE, WOR, and ER were markedly different ( P < 0.05) between the two groups after NAC. Also, at the threshold values of 3.2%/s, 175 s, and 5.4% (slope, TTP, and ER), the sensitivity and specificity for predicting good response to chemotherapy were 83.3% and 92.3%, 91.7% and 69.2%, 84.6% and 75.0%, respectively. Conclusion Slope, TTP, and ER values could be used to evaluate and predict the response to NAC in osteosarcoma.

Modeling the Effectiveness of TV and Social Media Advertisements on the Dynamics of Water-Borne Diseases

Cholera is a serious threat to the health of human-kind all over the world and its control is a problem of great concern. In this context, a nonlinear mathematical model to control the prevalence of cholera disease is proposed and analyzed by incorporating TV and social media advertisements as a dynamic variable. It is considered that TV and social media ads propagate the knowledge among the people regarding the severe effects of cholera disease on human health along with its precautionary measures. It is also assumed that the mode of transmission of cholera disease among susceptible individuals is due to consumption of contaminated drinking water containing Vibrio cholerae. Moreover, the propagation of knowledge through TV and social media ads makes the people aware to adopt precautionary measures and also the aware people make some effectual efforts to washout the bacteria from the aquatic environment. Model analysis reveals that increase in the washout rate of bacteria due to aware individuals causes the stability switch. It is found that TV and social media ads have the potential to reduce the number of infectives in the region and thus control the cholera epidemic. Numerical simulation is performed for a particular set of parameter values to support the analytical findings.

Prognostic value of myocardial MIBG scintigraphy in acute ischemic stroke

Funding Acknowledgements Type of funding sources: None. Background Autonomic dysfunction is a common complication of acute ischemic stroke and has been associated with poor functional outcome and increased mortality. We investigated the potential relation between the myocardial washout rate (WOR) of 123I-meta-iodobenzylguanidine (123I-mIBG), as a measure of cardiac sympathetic activity, and functional outcome in acute ischemic stroke. Methods 38 patients with ischemic stroke (11 females, 72 years old [61-81)), underwent myocardial 123I-mIBG scintigraphy within the first week after stroke onset. Early (10 minutes post-injection (pi)) and late (4 hours pi) planar scans of the thoracic region were made. Regions of interest (ROI) were drawn over the mediastinum and the heart, and heart-to-mediastinum ratio (HMR) was calculated. Myocardial WOR was calculated as follows: (ROI heart early – ROI heart late)/ (ROI heart early) x 100%. Counts were corrected for background and counts in ROI heart late were corrected for decay. Patients were divided in 2 groups: those with a good functional outcome, defined as modified Rankin Scale (mRS) ≤ 2 at 3 months after stroke (i.e., patient is functionally independent), and those with a poor functional outcome, defined as a mRS &gt; 2. Results Median WOR was 27,4 % (IQR 10,4-43,6). In univariate analysis, poor functional outcome after stroke was associated with age, stroke severity on admission (measured by the National Institutes of Health Stroke Scale (NIHSS)), beta-blocker use before and during hospitalization, WOR and late HMR. In subsequent multivariate analysis WOR (OR 1.087; 95% CI 1.003-1.177, p = 0.042) was an independent predictor of poor stroke outcome even after adjustment for age and NIHSS. Conclusions In patients with acute ischemic stroke, myocardial washout of 123I-mIBG predicts stroke outcome, even after adjustment for age and stroke severity on admission.

Value of cardiac 123I-mIBG scintigraphy in prognosis of catheter ablation outcome in patients with atrial fibrillation

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Science Foundation Background. Previous studies show inconsistent results on the role of innervation imaging (with 123I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF. Thus, the goal of the present study was to estimate the utility of pre-procedural cardiac 123I-mIBG scintigraphy to identify patients at risk for AF recurrence after CA. Methods. 123I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patients were followed for 12 months. A blanking period of 3 months was applied. The primary endpoint of the study was AF recurrence between 3 and 12 months after ablation. Results. Multivariable analysis demonstrated that late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/Mlate &lt;1.6 (sensitivity 73.53 %, specificity 81.3%, AUC 0,792 , p &lt; 0.001) and WR &gt; 25,11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0,712 , p &lt; 0.001) indicate high probability of AF relapses during 12 months after CA. Kaplan-Meier analysis showed that the H/Mlate &lt; 1.6, WR &gt; 25,11 and LAD &gt; 45 mm significantly increase the risk of AF recurrence after CA (p &lt; 0.001, p &lt; 0.001, p &lt; 0.025 respectively). Conclusion. Pre CA parameters of global cardiac sympathetic activity estimated by 123I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients.

The utility of dynamic MRI in differentiating the hormone-producing ability of pituitary adenomas

Purpose To investigate the relationship between dynamic magnetic resonance imaging (MRI) findings and hormonal activity in pituitary adenomas. Methods We retrospectively evaluated the dynamic MRI findings in 244 patients with pathologically confirmed pituitary adenomas and a diagnosis of clinically active prolactin (PRL)-producing adenomas. Among the 244 pituitary adenomas, 55, 16, 6, and 4 produced growth hormone (GH), PRL, adrenocorticotropic hormone, and thyroid-stimulating hormone, respectively, while 163 were non-functioning (NF) adenomas. For each adenoma, we calculated the washout rate (WR) and early (EER) and delayed (DER) tumour-to-normal-tissue enhancement ratios. Results The respective mean values of the WR, EER, and DER were 9.4%, 75.2%, and 64.5% for GH-producing adenomas; 6.2%, 117.1%, and 106.2% for PRL-producing adenomas; and 5.4%, 116.7%, and 108.7% for NF adenomas. GH-producing adenomas had significantly lower EER and DER values than PRL-producing (P < 0.001) and NF adenomas (P < 0.001). In ROC analysis of GH-producing and non-GH-producing adenomas, the areas under the curves of WR, EER, and DER were 0.593, 0.825, and 0.857, respectively. Conclusion There are differences in dynamic MRI features between GH-producing and non-GH-producing adenomas, which suggests that EER and DER may be useful for diagnosing GH-producing adenomas.

The value of myocardial MIBI washout rate in risk stratification of coronary artery disease

Background Although it is well established that MIBI does not redistribute as thallium within the myocardium, it showed a reverse redistribution phenomenon that can be expressed by the rate of myocardial MIBI washout. The aim in this study was calculating the global myocardial washout of the MIBI (GWR) in patients diagnosed with coronary artery disease (CAD) of different risk stratifications. Results This prospective study included 100 patients. All patients were stratified into low-, intermediate-, and high-risk groups according to clinical evaluation using Framingham score, stress ECG results using Duke’s score and finally myocardial perfusion imaging prognostic findings. GWR was estimated in each of these groups. GWR mean was 9.5%, 13%, and 18% within clinically stratified patients into low-, intermediate-, and high-risk patients respectively with correlation coefficient 0.4. In addition, GWR mean was 9.7%, 15.4%, and 18.7% within patients stratified according to exercise ECG findings into low-, intermediate-, and high-risk patients respectively with correlation coefficient 0.6. Combining all myocardial perfusion findings, GWR mean was 7.9%, 15.1%, and 19.3% in patient with low-, intermediate-, and high-risk imaging findings respectively with correlation coefficient 0.71. Conclusion GWR is positively correlated with the risk stratifications of the CAD patients. GWR can be used as an additional parameter to assess the risk of CAD patients.

Prognosis of atrial fibrillation radiofrequency ablation: Iodine-123-MIBG cardiac innervation imaging

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Science Foundation BACKGROUND To date, radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is a valuable treatment option. So far there are no clear predictors of the effectiveness of AF ablation. Nowadays, the association of cardiac sympathetic nervous system and the development and maintenance of AF has been showed. The association between сardiac sympathetic system impairment, assessed by 123I-MIBG scintigraphy and RFCA effectiveness was shown previously. However, the is lack of data concerning to prognostic value of MIBG scintigraphy in patients with different forms of AF – persistent (PAF) and long-standing persistent (LSPAF). PURPOSE To study the prognostic significance of 123I-MIBG scintigraphy in RFCA efficacy in patients with persistent and long-standing persistent AF. METHODS The study enrolled 36 patients with drug-resistant AF (both persistent (n = 20) and long-standing persistent (n = 16) forms). All patients had comorbidity as chronic coronary syndrome and hypertension. A comparison group (n = 10) was also enrolled in the study. It includes patients with chronic coronary syndrome and arterial hypertension (without arrhythmia). All patients underwent 123I-MIBG and 99mTc-MIBI scintigraphy to evaluate the cardiac sympathetic activity and myocardial perfusion, respectively. Patients with AF performed RFCA. After of 1 year follow-up patients were examined for AF recurrence. The AF recurrence was considered to be an AF of at least 30 sec duration on a 12-lead ECG or on the Holter monitoring. RESULTS During the follow-up period, AF recurrences were reported in 7 (35%) PAF patients and in 8 (50%) LSPAF patients. According to multivariate analysis only a high pre-ablation washout rate of 123I-MIBG (WR) in PAF patients (OR: 1.668; 95% CI: 1.093–2.548) and large pre-ablation 123I-MIBG/99mTc-MIBI mismatch score in LSPAF patients (OR: 2.155; 95% CI: 1.192–3.897) were independent predictors of AF recurrence after RFCA. ROC analysis indicated that in PAF patients with higher WR ≥ 20.8% (AUC: 0.968; Sensitivity: 100 %; Specificity: 45%; p &lt; 0.05) and LSPAF patients with larger 123I-MIBG/99mTc-MIBI mismatch score ≥ 12.5 % (AUC: 0.942; Sensitivity: 81 %; Specificity: 28 %; p &lt; 0.05) had a higher risk of AF recurrence after RFCA. CONCLUSION In AF patients the incidence of arrhythmia recurrence after RFCA is associated with impaired cardiac sympathetic nervous activity. In PAF patients the values of 123I-MIBG washout rate can predict AF recurrence. In LSPAF patients innervation/perfusion mismatch has prognostic value in terms of AF recurrence.