Standard Clinical Protocol Research Articles

Characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1 using heterogeneity analysis of 18F-FDG PET

PurposeMeasurement of heterogeneity in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images is reported to improve tumour phenotyping and response assessment in a number of cancers. We aimed to determine whether measurements of 18F-FDG heterogeneity could improve differentiation of benign symptomatic neurofibromas from malignant peripheral nerve sheath tumours (MPNSTs).Methods18F-FDG PET data from a cohort of 54 patients (24 female, 30 male, mean age 35.1 years) with neurofibromatosis-1 (NF1), and clinically suspected malignant transformation of neurofibromas into MPNSTs, were included. Scans were performed to a standard clinical protocol at 1.5 and 4 h post-injection. Six first-order [including three standardised uptake value (SUV) parameters], four second-order (derived from grey-level co-occurrence matrices) and four high-order (derived from neighbourhood grey-tone difference matrices) statistical features were calculated from tumour volumes of interest. Each patient had histological verification or at least 5 years clinical follow-up as the reference standard with regards to the characterisation of tumours as benign (n = 30) or malignant (n = 24).ResultsThere was a significant difference between benign and malignant tumours for all six first-order parameters (at 1.5 and 4 h; p < 0.0001), for second-order entropy (only at 4 h) and for all high-order features (at 1.5 h and 4 h, except contrast at 4 h; p < 0.0001–0.047). Similarly, the area under the receiver operating characteristic curves was high (0.669–0.997, p < 0.05) for the same features as well as 1.5-h second-order entropy. No first-, second- or high-order feature performed better than maximum SUV (SUVmax) at differentiating benign from malignant tumours.Conclusions18F-FDG uptake in MPNSTs is higher than benign symptomatic neurofibromas, as defined by SUV parameters, and more heterogeneous, as defined by first- and high-order heterogeneity parameters. However, heterogeneity analysis does not improve on SUVmax discriminative performance.

Could neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLT), and lymphocyte to monocyte ratio be common independent prognostic factors in head and neck squamous cell carcinoma?

e17519 Background: The purpose of our study was to investigate prognostic role of neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio in PFS and OS, and immunological tumor’s microenvironment in patient with HNSCC. Methods: We analysed medical records an tumor samples of 60 patients with HNSCC with stage I - IVB (37 men, 23 women; median age 59). All patients were under standard clinical complex protocol. All patients were under our supervision from 2010 to 2015. We examined demographic data, clinical stage, tumor morphological characteristics and specific level of expression of CD8(+) T-cells, in the tumor and microenvironment, and baseline level of WBC, neutrophil, lymphocyte, monocyte and PLT . Also we analysed calculated value of NLR, dNLR, PLR, and LMR. Results: The median value of NLR was 2.03 (95% CI: 1.66-2.59), dNLR - 1.44 (95% CI: 1.23-1.70), PLR - 144.58 (95% CI: 107.59-179.32) and LMR - 6.79 (95% CI: 5.34-8.17). Median of 1-year OS and PFS was non significantly lower in pts with NLR &lt; 2.03 (16.0 vs 18.0 month, p = 0.6020 and 5.00 vs 7.00 month, p = 0.5383). But NLR correlate with expression of CD8(+) T-cell in tumor (p = 0.05). Median of 1-year OS was the same in both group (16.0 vs 17.0 month, p = 0.5453), PFS was non significantly lower in pts with dNLR &lt; 1.44 (16.0 vs 18.0 month, p = 0.6020 and (5.00 vs 7.00 month, p = 0.7435). NLR correlate with expression of CD8(+) T-cell in tumor (p = 0.0337). Analyse of LMR showed trend of best 1-year OS in pts with LMR &lt; 6.79 (18.0 vs 15.0 month, p = 0.4674) and equal PFS (6.00 vs 7.00 month, p = 0.4914). PFS and 1-year OS were better (nonsignificant) in pts with PLT &gt; 144.58 (9.0 vs 5.0 month, p = 0.5854) and (18.0 vs 16.0 month, p = 0.5836). Conclusions: Important role of indicators of systemic inflammation is obvious for patient with HNSCC, but our study showed that only baseline characteristics couldn’t be strong prognostic factors by different degree of intratumor inflammation.

Hyperbaric oxygen therapy for wound healing in diabetic rats: Varying efficacy after a clinically-based protocol.

Hyperbaric oxygen therapy (HBOT) is a clinical treatment in which a patient breathes pure oxygen for a limited period of time at an increased pressure. Although this therapy has been used for decades to assist wound healing, its efficacy for many conditions is unproven and its mechanism of action is not yet fully clarified. This study investigated the effects of HBOT on wound healing using a diabetes-impaired pressure ulcer rat model. Seven weeks after streptozotocin-induced diabetes in rats (n = 55), a pressure ulcer was created on dorsal skin. Subsequently, animals received HBOT during 6 weeks following a standard clinical protocol (HBOT group with varying endpoints up to 42 days post-wounding) versus controls without HBOT. Capillary venous oxygen saturation (SO2) showed a significant increase in the HBOT group on day 24; however, this increase was significant at this time point only. The quantity of hemoglobin in the micro-blood vessels (rHB) showed a significant decrease in the HBOT group on days 21 and 42, and showed a trend to decrease on day 31. Blood flow in the microcirculation showed a significant increase on days 17, 21 and 31 but a significant decrease on days 24 and 28. Inflammation scoring showed significantly decreased CD68 counts in the HBOT group on day 42, but not in the early stages of wound healing. Animals in the HBOT group showed a trend for an increase in mean wound breaking strength on day 42.

Effect of applied voltage, duration and repetition frequency of RF pulses for pain relief on temperature spikes and electrical field: a computer modelling study

Background: The thermal and electrical effects of pulsed radiofrequency (PRF) for pain relief can be controlled by modifying the characteristics of the RF pulses applied. Our goal was to evaluate the influence of such modifications on the thermal and electric performance in tissue.Methods: A computational model was developed to compare the temperature and electric field time courses in tissue between a standard clinical protocol (45 V pulses, 20 ms duration, 2 Hz repetition frequency) and a new protocol (55 V pulses, 5 ms duration, 5 Hz repetition frequency) with a higher applied electric field but a smaller impact on temperature alterations in tissue. The effect of including a temperature controller was assessed. Complementarily, an agar-based experimental model was developed to validate the methodology employed in the computer modelling.Results: The new protocol increased the electric field magnitude reached in the tissue by around +20%, without increasing the temperature. The temperature controller was found to be the fundamental factor in avoiding thermal damage to the tissue and reduced the total number of pulses delivered by around 67%. The experimental results matched moderately well with those obtained from a computer model built especially to mimic the experimental conditions.Conclusions: For the same delivered energy, the new protocol significantly increases the magnitude of the applied electric field, which may be the reason why it is clinically more effective in achieving pain relief.

Organ dose measurement using Optically Stimulated Luminescence Detector (OSLD) during CT examination

This study provides detailed information regarding the imaging doses to patient radiosensitive organs from a kilovoltage computed tomography (CT) scan procedure using OSLD. The study reports discrepancies between the measured dose and the calculated dose from the ImPACT scan, as well as a comparison with the dose from a chest X-ray radiography procedure. OSLDs were inserted in several organs, including the brain, eyes, thyroid, lung, heart, spinal cord, breast, spleen, stomach, liver and ovaries, of the RANDO phantom. Standard clinical scanning protocols were used for each individual site, including the brain, thyroid, lung, breast, stomach, liver and ovaries. The measured absorbed doses were then compared with the simulated dose obtained from the ImPACT scan. Additionally, the equivalent doses for each organ were calculated and compared with the dose from a chest X-ray radiography procedure. Absorbed organ doses measured by OSLD in the RANDO phantom of up to 17mGy depend on the organ scanned and the scanning protocols used. A maximum 9.82% difference was observed between the target organ dose measured by OSLD and the results from the ImPACT scan. The maximum equivalent organ dose measured during this experiment was equal to 99.899 times the equivalent dose from a chest X-ray radiography procedure. The discrepancies between the measured dose with the OSLD and the calculated dose from the ImPACT scan were within 10%. This report recommends the use of OSLD for measuring the absorbed organ dose during CT examination.

Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression

Introduction: Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivates the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine's antidepressant effects. Methods: Patients who were pursuing ketamine infusion therapy for treatment-resistant depression were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol. Results: Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first 2 weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine nonresponders did not appear to benefit from CBT. Conclusions: CBT may sustain the antidepressant effects of ketamine in treatment-resistant depression. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine's antidepressant effects.

EP-1455: IGRT kV-CBCT dose calculations using Virtual Source Models and validated in phantoms using OSL

Purpose or Objective: With the growing use of X-ray imaging equipment in Image-Guided RadioTherapy (IGRT), the need to evaluate the dose-to-organs delivered by kV-CBCT imaging acquisition increases. This study aims to propose accurate Monte Carlo (MC) calculations of the patient dose-to-organs delivered by two commercially available kV-CBCT systems: the XVI from Elekta’s VERSA HD accelerator and the OBI from Varian’s TrueBeam system. Simulations are to be validated using in phantom OSL measurements. Material and Methods: For both kV-CBCT systems, the kV irradiation head geometry was implemented in the MC simulation code Penelope. As a first step, the resulting photon distributions were expressed as Virtual Source Models (VSM) for every standard irradiation condition (kVp, filtration, collimation); it was then validated and adjusted using in water-phantom measurements performed with a calibrated Farmer-type ionization chamber. In a second step, the validated VSMs were used to simulate the dose delivered by both the XVI and OBI systems in anthropomorphic phantoms, using standard clinical imaging protocols. Simulated dose-to-organs were then confronted to dose measurements performed using OSL inserted into the same phantoms, following a dosimetric protocol for OSLs previously established [1]. In addition, VSM results were confronted to their direct MC counterparts in order to evaluate the benefit of using such technique. Results: The current study highlights the possibility to reproduce OSL dose-to-organ measurements using VSM-driven Monte Carlo simulation with an overall agreement better than 20 %. In addition, the use of VSM in the MC simulation enables to speed-up the calculation time by a factor better than two (for the same statistical uncertainty) compared to direct MC simulation. Nevertheless, if direct and VSM calculations are in agreement inside the irradiation field, outside, VSM results tend to be significantly lower (10-30%). Conclusion: The use of a VSM was demonstrated to simplify and fasten MC simulations for personalized kV-CBCT MC dose estimation. In addition, OSLs enable to perform the low dose measurement in the kV range needed for in phantom X-ray imaging equipment dose QA. This study is to be completed in the near future by the addition of other standard X-ray imaging equipment dedicated to IGRT.

The effect of post-injection 18F-FDG PET scanning time on texture analysis of peripheral nerve sheath tumours in neurofibromatosis-1

BackgroundTexture features are being increasingly evaluated in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) as adjunctive imaging biomarkers in a number of different cancers. Whilst studies have reported repeatability between scans, there have been no studies that have specifically investigated the effect that the time of acquisition post-injection of 18F-FDG has on texture features. The aim of this study was to investigate if texture features change between scans performed at different time points post-injection.ResultsFifty-four patients (30 male, 24 female, mean age 35.1 years) with neurofibromatosis-1 and suspected malignant transformation of a neurofibroma underwent 18F-FDG PET/computed tomography (CT) scans at 101.5 ± 15.0 and 251.7 ± 18.4 min post-injection of 350 MBq 18F-FDG to a standard clinical protocol. Following tumour segmentation on both early and late scans, first- (n = 37), second- (n = 25) and high-order (n = 31) statistical features, as well as fractal texture features (n = 6), were calculated and a comparison was made between the early and late scans for each feature.Of the 54 tumours, 30 were benign and 24 malignant on histological analysis or on clinical follow-up for at least 5 years. Overall, 25/37 first-order, 9/25 second-order, 13/31 high-order and 3/6 fractal features changed significantly (p < 0.05) between early and late scans. The corresponding proportions for the 30 benign tumours alone were 22/37, 7/25, 8/31 and 2/6 and for the 24 malignant tumours, 11/37, 6/25, 8/31 and 0/6, respectively.ConclusionsSeveral texture features change with time post-injection of 18F-FDG. Thus, when comparing texture features in intra- and inter-patient studies, it is essential that scans are obtained at a consistent time post-injection of 18F-FDG.

Estimating breast tumor blood flow during neoadjuvant chemotherapy using interleaved high temporal and high spatial resolution MRI.

To evaluate an interleaved MRI sampling strategy that acquires both high temporal resolution (HTR) dynamic contrast-enhanced (DCE) data for quantifying breast tumor blood flow (TBF) and high spatial resolution (HSR) DCE data for clinical reporting, following a single standard injection of contrast agent. A simulation study was used to evaluate the performance of the interleaved technique under different conditions. In a prospective clinical study, 18 patients with primary breast cancer, who were due to undergo neoadjuvant chemotherapy (NACT), were examined using interleaved HTR and HSR DCE-MRI at 1.5 Tesla. Tumor regions of interest were analyzed with a two-compartment tracer kinetic model. Paired parameters (n = 10) from the data acquired before and post-cycle 2 of NACT were compared using the nonparametric Wilcoxon signed-rank test. Simulations demonstrated that TBF was reliably estimated using the proposed strategy. The region of interest analysis revealed significant changes in TBF (0.81-0.43 mL/min/mL; P = 0.002) following two cycles of NACT. The HSR data were reported in the normal way and enabled the assessment of tumor volume, which decreased by 53% following NACT (P = 0.065). TBF can be measured reliably using the proposed strategy without compromising a standard clinical protocol. Furthermore, in our feasibility study, TBF decreased significantly following NACT, whereas capillary permeability surface-area product did not. Magn Reson Med 79:317-326, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Artifact in Pediatric Oculomotor Findings during Videonystagmography: A Retrospective Analysis.

Accurate measurement of oculomotor function using videonystagmography (VNG) is imperative for diagnosis and management of patients with reported dizziness. The oculomotor evaluation during VNG utilizes video-oculography providing valuable information regarding the central structures and pathways that control eye movements. Artifact may have an effect on the overall validity and reliability of VNG oculomotor tracings and can result from patient and/or recording errors. It is postulated that artifact could occur more frequently in the pediatric population due to both patient and equipment factors. The purpose of this study was to systematically evaluate the occurrence and impact of artifact on saccades, smooth pursuit, and optokinetic (OPK) testing in normal pediatric and adult subjects using commercially available clinical VNG equipment and standard clinical protocols for oculomotor testing. The present study utilized a retrospective analysis of a repeated measures design. Oculomotor results from a total of 62 participants were analyzed. Portions of these data have been presented in a previous research study. Group 1 consisted of twenty-nine 4- to 6-yr-olds with an average age of 4.86 (SD = 0.88) yr. Group 2 consisted of thirty-three 22- to 44-yr-olds with an average age of 25.2 (SD = 5.34) yr. Raw oculomotor recordings were analyzed "offline" by a single masked, trained investigator. Each tracing was evaluated for instances of artifact including eye blinks, eye closure, eyes moving in opposite direction of the target, eye tracking software problems, and overall poor morphology. The number of instances of artifact were noted and recorded for each participant in both groups. Individual eye movements not affected by artifact were included for final analysis. Artifact rejection techniques were also compared. The results indicated increased artifact for the pediatric group for saccade and smooth pursuit testing. Additionally, a significant decrease in instances of artifact was noted with an increase in age in months for both saccade and smooth pursuit findings. OPK results did not indicate any significant difference in instances of artifact between the pediatric and adult groups or any decrease in instances of artifact with increasing age in the pediatric group. Artifact rejection technique did not have a significant effect on oculomotor measures for either age group. Pediatric patients exhibit increased instances of artifact during VNG oculomotor testing, specifically during saccade and smooth pursuit testing, at least for the 4- to 6-yr-old population. A general age effect was also noted in this age group, with decreased artifact noted with increasing age. Artifact rejection technique was not a significant factor suggesting standard compared based strategies may be sufficient for use in the pediatric population. Additional study into the effect of artifact on oculomotor results for infants to age 3 yr and ages 7- to 18-yr-old, in the disordered population, and with additional equipment manufacturers is needed to confirm these results and further describe the impact of artifact on oculomotor findings in the pediatric population.

Teaching of Pneumonia on a Cycle of Specialization “General Practice – Family Medicine”

Pneumonia remains an urgent medical and social problem. The urgency of this problem is not stressed by only the significant prevalence, but also by quite high rates of morbidity and mortality and significant economic losses due to this disease.The purpose of work is to improve the quality of the training for interns – on the specialty “General Practice – Family Medicine” by improving the teaching of the topic “Pneumonia” and practical classes.Discussion. Postgraduate education includes training of medical interns – general practitioners to work independently on primary health care. Great importance in the education of interns – general practitioners is given to the development of practical skills.Conclusion. Further improvement of practical training of interns – general practitioners on the specialty “Pneumonia”, perfection of practical training of a doctor – is a complex process that requires not only organizational measures, improvement and specification of standardized clinical protocols, textbooks, but also continuous improvement of academic, medical diagnostic, educational work, materials and technical support of study.

Coronary CT angiography in the emergency department utilizing second and third generation dual source CT

BackgroundCoronary computed tomography angiography (coronary CTA) allows efficient triage of low to intermediate risk patients with suspected acute coronary syndrome (ACS) in the emergency department (ED). Techniques for coronary CTA acquisition in the ED continue to evolve with the establishment of standardized scan protocols and the introduction of newer generations of CT hardware. ObjectivesTo evaluate qualitative and quantitative image quality and radiation dose exposure of coronary CTA acquired on 2nd versus 3rd generation dual source CT (DSCT) scanners using a standardized institutional scan protocol designed for the ED. MethodsA retrospective observational case-control study was performed of 246 ED patients referred to coronary CTA with suspicion of ACS (56.5% male; mean age 53.3 ± 11.6 years) between October 2013 and August 2015.123 consecutive patients were scanned on 3rd generation DSCT, and a cohort of 123 patients matched by age, BMI and heart rate were identified who had undergone 2nd generation DSCT imaging utilizing the same standard clinical protocol. Qualitative and quantitative image quality parameters and radiation exposures were evaluated. ResultsQualitative image quality was significantly higher using 3rd generation DSCT as compared to 2nd generation (p < 0.001). Mean attenuation in the proximal coronary arteries was also significantly higher on 3rd generation DSCT than for 2nd generation (586 HU vs. 426 HU in the left main coronary artery (LM), p < 0.001). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values, however, were lower in 3rd generation DSCT than 2nd generation (SNR 11.2 [9.9–13.4] vs 13.5 [11.0–15.5] and CNR 12.4 [10.9–14.8] vs 15.2 [12.8–17.9] in the LM, p < 0.001). Median effective dose was also lower for 3rd generation DSCT than for 2nd generation (2.9 [2.3–5.0] mSv and 3.7 mSv [2.5–5.7], respectively) although this trend did not reach statistical significance (p = 0.065). ConclusionQualitative image quality and mean CT attenuation values of the assessed coronary segments were significantly higher using 3rd generation DSCT. SNR and CNR were lower on 3rd generation DSCT, however this was accompanied by a trend toward lower radiation dose exposure when using the same standard institutional protocol.

Approaches to Optimize Gene Therapy for the Treatment of Hematologic Malignancies: Overcoming the Obstacles

Gene transfer and oncolytic viruses provide new therapeutic approaches for the treatment of hematologic malignancies. However, it is still too early to introduce gene delivery or oncolytic viruses into standard clinical protocol. It is very important to discuss the obstacles that gene transfer and oncolytic virotherapy face for the further clinical application for the treatment of hematologic malignancies, and updating the advances made to overcome them. The major concerns in this review include the approaches of the development of immuno-stimulatory gene transfer mediated-vaccination for leukemia therapy, RNAi-based therapy for leukemia and enhancement of sensitivity of target malignant cells to virotherapy and alteration of host immune response to favor oncolytic viruses. We conclude with a perspective on the future of the gene therapy and virotherapy for the treatment of hematologic malignancies, emphasizing the problems we should solve and the technological requirements for further clinical applications.

The Italian Neuroimaging Network Initiative (INNI): enabling the use of advanced MRI techniques in patients with MS.

Magnetic resonance imaging (MRI) is an important paraclinical tool to diagnose and monitor multiple sclerosis (MS). Conventional MRI measures lack of pathological specificity and are weakly correlated with MS clinical manifestations. Advanced MRI techniques are improving the understanding of the mechanisms underlying tissue injury, repair, and functional adaptation in MS; however, they require careful standardization. The definition of standardized methods for the collection and analysis of advanced MRI techniques is central not only to improve the understanding of disease pathophysiology and evolution, but also to generate research hypotheses, monitor treatment, increase cost-effectiveness and power of clinical trials. We promoted the Italian Neuroimaging Network Initiative (INNI), involving centers and investigators with an International recognized expertise, with the major goal to determine and validate novel MRI biomarkers to be utilized as predictors and/or outcomes in future MS studies. The INNI initiative supported the creation of a centralized repository, where advanced structural and functional MRI scans available at the participating sites, with the related clinical and neuropsychological data, are collected. These data will be used to perform research studies to identify clinical, neuropsychological and imaging biomarkers characteristics of the entire spectrum of MS. INNI will be instrumental to help to define standardized MRI and clinical protocols towards an increasing uptake of personalized interventions for people with MS at a national and international level. Upon approval of the INNI Steering Committee, the data collected in the online database will be shared with any research center detailing specific research proposals on disease pathophysiology or treatment effects.

Evaluation of MLACF based calculated attenuation brain PET imaging for FDG patient studies

Calculating attenuation correction for brain PET imaging rather than using CT presents opportunities for low radiation dose applications such as pediatric imaging and serial scans to monitor disease progression. Our goal is to evaluate the iterative time-of-flight based maximum-likelihood activity and attenuation correction factors estimation (MLACF) method for clinical FDG brain PET imaging. FDG PET/CT brain studies were performed in 57 patients using the Biograph mCT (Siemens) four-ring scanner. The time-of-flight PET sinograms were acquired using the standard clinical protocol consisting of a CT scan followed by 10 min of single-bed PET acquisition. Images were reconstructed using CT-based attenuation correction (CTAC) and used as a gold standard for comparison. Two methods were compared with respect to CTAC: a calculated brain attenuation correction (CBAC) and MLACF based PET reconstruction. Plane-by-plane scaling was performed for MLACF images in order to fix the variable axial scaling observed. The noise structure of the MLACF images was different compared to those obtained using CTAC and the reconstruction required a higher number of iterations to obtain comparable image quality. To analyze the pooled data, each dataset was registered to a standard template and standard regions of interest were extracted. An SUVr analysis of the brain regions of interest showed that CBAC and MLACF were each well correlated with CTAC SUVrs. A plane-by-plane error analysis indicated that there were local differences for both CBAC and MLACF images with respect to CTAC. Mean relative error in the standard regions of interest was less than 5% for both methods and the mean absolute relative errors for both methods were similar (3.4% ± 3.1% for CBAC and 3.5% ± 3.1% for MLACF). However, the MLACF method recovered activity adjoining the frontal sinus regions more accurately than CBAC method. The use of plane-by-plane scaling of MLACF images was found to be a crucial step in order to obtain improved activity estimates. Presence of local errors in both MLACF and CBAC based reconstructions would require the use of a normal database for clinical assessment. However, further work is required in order to assess the clinical advantage of MLACF over CBAC based method.

Vitamin B12 and Homocysteine Associations with Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging.

This study aimed to assess the independent associations of serum levels of vitamin B12 and plasma concentrations of homocysteine with gait speed decline. This study utilized longitudinal analysis of participants 50 years or older from The Baltimore Longitudinal Study of Aging, N=774. Gait speed (m/s) was assessed using the 6-meter usual pace test. Vitamin B12 and homocysteine concentrations were collected using standard clinical protocols. Linear mixed effects regression was stratified by baseline age category (50-69, 70-79, and ≥80 years old). Mean follow-up time for the total study sample was 5.4 ± 2.0 years. No association between vitamin B12 and gait speed decline over the follow-up time for any age group was found. Elevated homocysteine concentrations were associated with decline in gait speed after adjustment for covariates (50-69: β= -0.005, p=.057; 70-79: β= -0.013, p<.001, ≥80: β= -0.007, p=.054). Homocysteine and vitamin B12 are inversely related, yet only homocysteine was associated with gait speed decline in this population of healthy older adults. Given these results, future research should be directed towards investigating the relationship in populations with greater variation in vitamin B12 concentrations and other mechanisms influencing homocysteine concentrations.

P084 Investigation of non-coding RNAs as molecular markers during glucocorticoid treatment in children with inflammatory bowel disease

Background: Despite the introduction of novel biological therapies, glucocorticoids (GCs) remain widely used for inducing remission in inflammatory bowel diseases (IBD), in particular for ulcerative colitis. Given the high incidence of suboptimal response, associated with a significant number of side effects, that are particularly severe in paediatric patients, the identification of subjects that are most likely to respond poorly to GCs is extremely important. In this context, recent results obtained in our laboratory suggest a role for the long noncoding RNA growth arrest-specific 5 (GAS5) in modulating GC response, suggesting that it could be considered a marker of GC resistance. To address this issue, we evaluated the association between the lncRNA GAS5 and the efficacy of steroids in IBD paediatric patients and by in vitro models. Methods: For the clinical studies, seventeen IBD paediatric patients treated with prednisone 1 to 2 mg/kg/day for 30 days, according to standard clinical protocol, were enrolled at the Paediatric Clinic of IRCCS Burlo Garofolo in Trieste. Peripheral blood was obtained from these patients at diagnosis (T0) and after 4 weeks of steroid treatment (T4). RNA was extracted from patients' peripheral blood mononuclear cells at T0 and T4, and used to analyze the levels of the lncRNA. Patients were classified on the basis of their clinical response into 3 groups: steroid resistant (SR), steroid sensitive (SS) and steroid dependent (SD). For the in vitro studies, the effect of methylprednisolone on the proliferation of HeLa and LoVo cells was determined by labelling metabolically active cells with [methyl-3H] thymidine, and the expression of GAS5 was determined by TaqMan® Assay. The localization of GAS5 during GC treatment was evaluated by subcellular fractionation and the functions of the lncRNA were assessed by silencing this lncRNA in vitro. Results: Among the 17 patients enrolled, 3 were SR, 8 SD and 6 SS; patients with unfavorable steroid response (SD + SR) presented higher GAS5 levels in comparison with SS group, supporting a contribution of GAS5 to steroid ineffectiveness. GAS5 was upregulated in GC resistant cells and accumulated more in the cytoplasm compared to the nucleus in response to the drug; in addition, GAS5 knock-down reduced the proliferation during GC treatment. Conclusions: We hypothesize that higher levels of GAS5 can result in the suppression of GC activity, and if these results are confirmed in a larger number of subjects, GAS5 should be considered a novel biomarker useful for the personalization of GC therapy in paediatric IBD patients and for elucidating the molecular pathways that underline GC resistance.

Primary health care providers' roles and responsibilities: A qualitative exploration of ‘who does what’ in the treatment and management of persons affected by obesity

ABSTRACTObesity is now considered a national epidemic. Guidelines to manage persons who are overweight or affected by obesity are available but rarely relevant and applicable to primary care clinicians’ expertise. A qualitative descriptive narrative approach was used to identify challenges of primary care professionals in regard to the management of obesity. A literature review was conducted and input from experts was integrated with findings from interviews with Primary-Care Physicians, Physician Assistants, Nurse Practitioners, and Patient Advocates. Transcripts were coded using a thematic analysis approach. Two main challenges, associated with communication among the primary care team and with patients, emerged: (1) a lack of interprofessional integration and; (2) challenges in conceptualizing obesity as a chronic condition, contributing to lack of proactivity and communication in treating and managing persons who are overweight or affected by obesity. A causal factor is the dearth of standardized procedures, applicable at a primary care level. Lack of systematic procedures for the communication with, and management of, persons who are overweight or affected by obesity, and of clearly delineated roles of each primary care team member can undermine continuous care, and can contribute to a sense of disempowerment for both providers and the patients. Both would, thus, benefit from standardized clinical protocols. Behavioral training to the primary care team would also facilitate the communication with at-risk patients and would provide guidance to address the psychological and behavioral aspects of being overweight or affected by obesity in order to facilitate lifestyle changes.

Ferumoxytol MRA for transcatheter aortic valve replacement planning with renal insufficiency

BackgroundComputed tomography angiography (CTA) is the test of choice for pre-procedure imaging of transcatheter aortic valve replacement (TAVR) candidates. The iodinated contrast required, however, increases the risk of renal dysfunction in patients with pre-existing renal failure. Ferumoxytol is a magnetic resonance imaging (MRI) contrast agent that can be used with renal failure. Its long vascular resonance time allows gated MRA sequences that approach CTA in image quality. We present respiratory and cardiac gated MRA enabled by ferumoxytol that can be post-processed in an analogous fashion to CTA. MethodsSeven patients with renal failure presenting for TAVR were imaged with respiratory and cardiac gated MRA at 3T using ferumoxtyol for contrast. Aortic annulus, root and peripheral access dimensions were calculated in a fashion identical to that used for CTA. Of these, 6 patients underwent a TAVR procedure and 5 had intraoperative valve assessment with transesophageal echocardiograph (TEE) using standard clinical protocols that employed both two- and three-dimensional techniques. ResultsGood correlation between MRA aortic annulus measurements and those from TEE were shown in 5 patients with mean annulus area of 392.4mm2 (290–470 range) versus 374.1mm2 (285–440 range), with a pairwise correlation coefficient of 0.92, p=0.029. All patients received Sapien valve implants (one 20mm, three 23mm, and two 26mm valves). Access decisions were guided by MRA with no complications. Annulus sizing resulted in no greater than trace/mild aortic regurgitation in all patients. ConclusionsFerumoxytol MRA is a safe alternative to CTA in patients with renal failure for pre-TAVR analysis of the aortic root and peripheral access.

Quiet MR sequences in clinical routine: initial experience in abdominal imaging.

Purpose of our study was to demonstrate the feasibility and limitations of acoustic noise reduction in a standard clinical MRI protocol for abdominal imaging. Acoustic noise and image quality were assessed in 17 patients for a standard liver imaging protocol including TSE and GRE sequences and compared to quiet optimizations as described by Heismann et al. Two blinded readers scored artifacts, the delineation of the abdominal organs and level of diagnostic confidence. Means of the sound level measurements, the ratings and the measurement of SNR and CNR were compared. Significant reduction of acoustic noise was measured for T2 TSE (-30.7%), T2 HASTE (-22.6%) and less difference for T1 DIXON (-4.7%) and T1 FLASH (-2.7%). SNR and CNR were lower for quiet T2 TSE (-18.0%, -23.1%) and T2 HASTE (-46.2%, -37.7%) and higher for T1 DIXON (+32.0%, +24.4%). Inter-rater correlation was k=0.987 with p<0.001. Although sequence-based noise optimizations faces problems in T1 FLASH and DIXON sequences, there is an important acoustic benefit in T2 TSE and T2 HASTE sequences, which goes along with a maintained image quality and diagnostic confidence.