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Τετάρτη, 6 Δεκεμβρίου 2017

Forensic 3D documentation of bodies: Simple and fast procedure for combining CT scanning with external photogrammetry data

Publication date: Available online 6 December 2017
Source:Journal of Forensic Radiology and Imaging
Author(s): Chiara Villa, Mitchell J. Flies, Christina Jacobsen
This study presents a procedure for combining 3D models obtained from CT scanning (internal and external data) and photogrammetry (external data). 3D data were acquired at different times, without the support of reference points. The procedure has been tested on 30 injured areas caused by different wounding mechanisms. The alignment of the different 3D models was in most of the cases very precisely (mean distance around 1mm, SD around or lower than 2mm). Ad hoc procedures should be followed in case of injuries on the head, joints and back.



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Review of Simulation Training in Interventional Radiology

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Publication date: Available online 6 December 2017
Source:Academic Radiology
Author(s): Souzan Mirza, Sriharsha Athreya
Simulation training has evolved and is now able to offer numerous training opportunities to supplement the practice of and overcome some of the shortcomings of the traditional Master-Apprentice model currently used in medical training. Simulation training provides new opportunities to practice skills used in clinical procedures, crisis management scenarios, and everyday clinical practice in a risk-free environment. Procedural and nonprocedural skills used in interventional radiology can be taught with the use of simulation devices and technologies. This review will inform the reader of which clinical skills can be trained with simulation, the types of commercially available simulators and their educational validity, and the assessment tools used to evaluate simulation training.



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Preventing Overdiagnosis of Acetabular Labral “Tears” in 40-Plus-year-old Patients

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Publication date: Available online 6 December 2017
Source:Academic Radiology
Author(s): Ian Amber, Suyash Mohan
Acetabular labral tears represent a common finding on magnetic resonance imaging of the hip. Labral tears can arise from a multitude of underlying pathological processes or they may be an asymptomatic incidental finding. The prevalence of labral tears and their lack of specificity make this an area vulnerable to potential overdiagnosis. The overdiagnosis of labral tears leads to overtreatment by exposing patients to unnecessary surgeries as well as complications ranging from unsatisfying outcomes to deep venous thrombosis. This risk is compounded by the tabloid popularization of labral surgeries by celebrities such as Lady Gaga, which could potentiate patient perception of a two-tiered level of health care. Following a similar situation with spine nomenclature, one solution to this issue is to reclassify "labral tears" as "labral fissures" in some or all cases to mitigate the acute traumatic connotation of the term "tear."



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Diagnostic Values of DCE-MRI and DSC-MRI for Differentiation Between High-grade and Low-grade Gliomas

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Publication date: Available online 6 December 2017
Source:Academic Radiology
Author(s): Jianye Liang, Dexiang Liu, Peng Gao, Dong Zhang, Hanwei Chen, Changzheng Shi, Liangping Luo
Rationale and ObjectivesThis study aimed to collect the studies on the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI) in differentiating the grades of gliomas, and evaluate the diagnostic performances of relevant quantitative parameters in glioma grading.Materials and MethodsWe systematically searched studies on the diagnosis of gliomas with DCE-MRI or DSC-MRI in Medline, PubMed, China National Knowledge Infrastructure database, Cochrane Library, and Embase published between January 2005 and December 2016. Standardized mean differences and 95% confidence intervals were calculated for volume transfer coefficient (Ktrans), volume fraction of extravascular extracellular space (Ve), rate constant of backflux (Kep), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) using Review Manager 5.2 software. Sensitivity, specificity, area under the curve (AUC), and Begg test were calculated by Stata 12.0.ResultsTwenty-two studies with available outcome data were included in the analysis. The standardized mean difference of Ktrans values between high-grade glioma and low-grade glioma were 1.18 (0.91, 1.45); Ve values were 1.43 (1.06, 1.80); Kep values were 0.65 (−0.05, 1.36); rCBV values were 1.44 (1.08, 1.81); and rCBF values were 1.17 (0.68, 1.67), respectively. The results were all significant statistically (P < .05) except Kep values (P = .07), and high-grade glioma had higher Ktrans, Ve, rCBV, and rCBF values than low-grade glioma. AUC values of Ktrans, Ve, rCBV, and rCBF were 0.90, 0.88, 0.93, and 0.73, respectively; rCBV had the largest AUC among the four parameters (P < .05).ConclusionBoth DCE-MRI and DSC-MRI are reliable techniques in differentiating the grades of gliomas, and rCBV was found to be the most sensitive one.



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Determinants of Difficulty and Discriminating Power of Image-based Test Items in Postgraduate Radiological Examinations

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Publication date: Available online 6 December 2017
Source:Academic Radiology
Author(s): Dirk R. Rutgers, Fleur van Raamt, Anouk van der Gijp, Christian Mol, Olle ten Cate
Rationale and ObjectivesThe psychometric characteristics of image-based test items in radiological written examinations are not well known. In this study, we explored difficulty and discriminating power of these test items in postgraduate radiological digital examinations.Materials and MethodsWe reviewed test items of seven Dutch Radiology Progress Tests (DRPTs) that were taken from October 2013 to April 2017. The DRPT is a semiannual formative examination, required for all Dutch radiology residents. We assessed several stimulus and response characteristics of test items. The response format of test items included true or false, single right multiple choice with 2, 3, 4, or ≥5 answer options, pick-N multiple-choice, drag-and-drop, and long-list-menu formats. We calculated item P values and item-rest-correlation (Rir) values to assess difficulty and discriminating power. We performed linear regression analysis in image-based test items to investigate whether P and Rir values were significantly related to stimulus and response characteristics. Also, we compared psychometric indices between image-based test items and text-alone items.ResultsP and Rir values of image-based items (n = 369) were significantly related to the type of response format (P < .001), and not to which of the seven DRPTs the item was obtained from, radiological subspecialty domain, nonvolumetric or volumetric character of images, or context-rich or context-free character of the stimulus. When accounted for type of response format, difficulty and discriminating power of image-based items did not differ significantly from text-alone items (n = 881). Test items with a relatively large number of answer options were generally more difficult, and discriminated better among high- and low-performing candidates.ConclusionIn postgraduate radiological written examinations, difficulty and discriminating power of image-based test items are related to the type of response format and are comparable to those of text-alone items. We recommend a response format with a relatively large number of answer options to optimize psychometric indices of radiological image-based test items.



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A method to combine target volume data from 3D and 4D planned thoracic radiotherapy patient cohorts for machine learning applications

The gross tumour volume (GTV) is predictive of clinical outcome and consequently features in many machine-learned models. 4D-planning, however, has prompted substitution of the GTV with the internal gross target volume (iGTV). We present and validate a method to synthesise GTV data from the iGTV, allowing the combination of 3D and 4D planned patient cohorts for modelling.

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Contrast-enhanced cone-beam breast-CT: Analysis of optimal acquisition time for discrimination of breast lesion malignancy

Publication date: Available online 6 December 2017
Source:European Journal of Radiology
Author(s): Johannes Uhlig, Uwe Fischer, Alexey Surov, Joachim Lotz, Susanne Wienbeck
ObjectiveTo investigate the optimal acquisition time of contrast-enhanced cone-beam breast-CT (CBBCT) for best discrimination of breast lesion malignancy and whether contrast enhancement can aid in classification of tumor histology.Material and MethodsThe study included patients with BI-RADS 4 or 5 lesions identified on mammography and/or ultrasound. All patients were examined by non-contrast (NC-CBBCT) and contrast-enhanced CBBCT (CE-CBBCT) at 2 and 3minutes (min) after CM injection. Lesion enhancement of suspicious breast lesions was evaluated in corresponding CBBCT slices.ResultsA total of 31 patients with 57 breast lesions, 30 malignant and 27 benign, were included. Malignant breast lesions demonstrated higher contrast enhancement than benign breast lesions at both 2min and 3min CE-CBBCT (2min: 48.17 vs. 0.3 HU, p<0.001; 3min: 57.38 vs. 15.43 HU, p<0.001). Enhancement differences between malignant and benign breast lesions were largest at 2min CE-CBBCT. Ductal carcinoma in situ (DCIS) showed highest mean contrast enhancement among malignant breast lesions (100.93 HU at 3min CE-CBBCT scan, p=0.0314) compared to invasive carcinoma of no special type with DCIS component (55.82 HU at 3min CE-CBBCT) and invasive ductal carcinoma (52.31 HU at 3min CE-CBBCT).ConclusionsThe contrast enhancement on CE-CBBCT best discriminates between malignant and benign breast lesions at 2min after CM injection. The enhancement has the potential to differentiate histopathological subtypes, with highest enhancement among malignant lesions seen for DCIS.



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Computer-Aided Diagnosis of Contrast-Enhanced Spectral Mammography: A Feasibility Study

Publication date: Available online 5 December 2017
Source:European Journal of Radiology
Author(s): Bhavika K. Patel, Sara Ranjbar, Teresa Wu, Barbara A. Pockaj, Jing Li, Nan Zhang, Mark Lobbes, Bin Zheng, J.Ross Mitchell
ObjectiveTo evaluate whether the use of a computer-aided diagnosis–contrast-enhanced spectral mammography (CAD-CESM) tool can further increase the diagnostic performance of CESM compared with that of experienced radiologists.Materials and MethodsThis IRB-approved retrospective study analyzed 50 lesions described on CESM from August 2014 to December 2015. Histopathologic analyses, used as the criterion standard, revealed 24 benign and 26 malignant lesions. An expert breast radiologist manually outlined lesion boundaries on the different views. A set of morphologic and textural features were then extracted from the low-energy and recombined images. Machine-learning algorithms with feature selection were used along with statistical analysis to reduce, select, and combine features. Selected features were then used to construct a predictive model using a support vector machine (SVM) classification method in a leave-one-out–cross-validation approach. The classification performance was compared against the diagnostic predictions of 2 breast radiologists with access to the same CESM cases.ResultsBased on the SVM classification, CAD-CESM correctly identified 45 of 50 lesions in the cohort, resulting in an overall accuracy of 90%. The detection rate for the malignant group was 88% (3 false-negative cases) and 92% for the benign group (2 false-positive cases). Compared with the model, radiologist 1 had an overall accuracy of 78% and a detection rate of 92% (2 false-negative cases) for the malignant group and 62% (10 false-positive cases) for the benign group. Radiologist 2 had an overall accuracy of 86% and a detection rate of 100% for the malignant group and 71% (8 false-positive cases) for the benign group.ConclusionsThe results of our feasibility study suggest that a CAD-CESM tool can provide complementary information to radiologists, mainly by reducing the number of false-positive findings.



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Relaxivity of Ferumoxytol at 1.5 T and 3.0 T

Objectives The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Materials and Methods Ferumoxytol was diluted in gradually increasing concentrations (0.26–4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. Results A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 s−1mM−1; r1plasma = 19.0 ± 1.7 s−1mM−1; r2saline = 60.8 ± 3.8 s−1mM−1; r2plasma = 64.9 ± 1.8 s−1mM−1; r2*saline = 60.4 ± 4.7 s−1mM−1; r2*plasma = 64.4 ± 2.5 s−1mM−1; 3.0 T: r1saline = 10.0 ± 0.3 s−1mM−1; r1plasma = 9.5 ± 0.2 s−1mM−1; r2saline = 62.3 ± 3.7 s−1mM−1; r2plasma = 65.2 ± 1.8 s−1mM−1; r2*saline = 57.0 ± 4.7 s−1mM−1; r2*plasma = 55.7 ± 4.4 s−1mM−1). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Conclusions Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization. Received for publication August 25, 2017; and accepted for publication, after revision, October 23, 2017. Conflicts of interest and sources of funding: This project received R&D grant support by the Departments of Radiology and Medical Physics, University of Wisconsin, as well as the NIH (K24 DK102595). Furthermore, the authors wish to acknowledge support from GE Healthcare and Bracco Diagnostics who provide research support to the University of Wisconsin. Author contributions: S.D.S. contributed to this work while at the University of Wisconsin–Madison. S.D.S. is currently an employee of Toshiba Medical Research Institute, USA. C.N.W. contributed to this work while at the University of Wisconsin–Madison. C.N.W. is currently an employee of Synaptive Medical, Canada. T.S. contributed to this work while at the University of Wisconsin–Madison. T.S. is currently an employee at the University Hospital Basel, Switzerland. Correspondence to: Gesine Knobloch, MD, Department of Radiology, School of Medicine and Public Health, Wisconsin Institute of Medical Research, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705. E-mail: gknobloch@wisc.edu. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Age-Related Changes in Tissue Value Properties in Children: Simultaneous Quantification of Relaxation Times and Proton Density Using Synthetic Magnetic Resonance Imaging

Objectives The properties of brain tissue undergo dynamic changes during maturation. T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) are now simultaneously quantifiable within a clinically acceptable time, using a synthetic magnetic resonance imaging (MRI) sequence. This study aimed to provide age-specific reference values for T1, T2, and PD in children, using synthetic MRI. Materials and Methods We included 89 children (median age, 18 months; range, 34 weeks of gestational age to 17 years) who underwent quantitative MRI, using a multidynamic, multiecho sequence on 3 T MRI, between December 2015 and November 2016, and had no abnormal MRI/neurologic assessment findings. T1, T2, and PD were simultaneously measured in each of the 22 defined white matter and gray matter regions of interest. The measured values were plotted against age, and a curve fitting model that best explained the age dependence of tissue values was identified. Age-specific regional tissue values were calculated using a fit equation. Results The tissue values of all brain regions, except cortical PD, decreased with increasing age, and the robust negative association was best explained by modified biexponential model of the form Tissue values = T1 × exp (−C1 × age) + T2 × exp (−C2 × age). The quality of fit to the modified biexponential model was high in white matter and deep gray matter (white matter, R2 = 97%–99% [T1], 88%–95% [T2], 88%–97% [PD]; deep gray matter, R2 = 96%–97% [T1], 96% [T2], 49%–88% [PD]; cortex, 70%–83% [T1], 87%–90% [T2], 5%–27% [PD]). The white matter and deep gray matter changed the most dynamically within the first year of life. Conclusions Our study provides age-specific regional reference values, from the neonate to adolescent, of T1, T2, and PD, which could be objective tools for assessment of normal/abnormal brain development using synthetic MRI. Received for publication September 7, 2017; and accepted for publication, after revision, October 22, 2017. Conflicts of interest and sources of funding: none declared. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (http://ift.tt/2kq7jVD). Correspondence to: Young Hun Choi, MD, Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110–769, Republic of Korea. E-mail: iater@snu.ac.kr. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Comment on “Indoor terrestrial gamma dose rate mapping in France: A case study using two different geostatistical models” by Warnery et al. (J. Environ. Radioact. 2015, 139, 140–148)

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Publication date: Available online 6 December 2017
Source:Journal of Environmental Radioactivity
Author(s): G.M. Kendall, M.P. Little, R. Wakeford




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Response to comment on "Indoor terrestrial gamma dose rate mapping in France: A case study using two different geostatistical models" by Warnery et al.

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Publication date: Available online 6 December 2017
Source:Journal of Environmental Radioactivity
Author(s): F. Marquant, C. Demoury, G. Ielsch, D. Laurier, D. Hémon, J. Clavel
Elements to answer the points raised in the Letter in question are proposed, notably about exposure metrics and their influence on the results and statistical power of epidemiological studies.



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Mapping of radiation anomalies using UAV mini-airborne gamma-ray spectrometry

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Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): Ondřej Šálek, Milan Matolín, Lubomír Gryc
Localization of size-limited gamma-ray anomalies plays a fundamental role in uranium prospecting and environmental studies. Possibilities of a newly developed mini-airborne gamma-ray spectrometric equipment were tested on a uranium anomaly near the village of Třebsko, Czech Republic. The measurement equipment was based on a scintillation gamma-ray spectrometer specially developed for unmanned aerial vehicles (UAV) mounted on powerful hexacopter. The gamma-ray spectrometer has two 103 cm3 BGO scintillation detectors of relatively high sensitivity. The tested anomaly, which is 80 m by 40 m in size, was investigated by ground gamma-ray spectrometric measurement in a detail rectangular measurement grid. Average uranium concentration is 25 mg/kg eU attaining 700 mg/kg eU locally. The mini-airborne measurement across the anomaly was carried out on three 100 m long parallel profiles at eight flight altitudes from 5 to 40 m above the ground. The resulting 1 s 1024 channel gamma-ray spectra, recorded in counts per second (cps), were processed to concentration units of K, U and Th, while total count (TC) was reported in cps. Increased gamma ray intensity of the anomaly was indicated by mini-airborne measurement at all profiles and altitudes, including the highest altitude of 40 m, at which the recorded intensity is close to the natural radiation background. The reported instrument is able to record data with comparable quality as standard airborne survey, due to relative sensitive detector, lower flight altitude and relatively low flight speed of 1 m/s. The presented experiment brings new experience with using unmanned semi-autonomous aerial vehicles and the latest mini-airborne radiometric instrument. The experiment has demonstrated the instrument's ability to localize size-limited uranium anomalies.



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Rapid and irreversible sorption behavior of 7Be assessed to evaluate its use as a catchment sediment tracer

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Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): N. Ryken, B. Al-Barri, W. Blake, A. Taylor, F.M.G. Tack, E. Van Ranst, S. Bodé, P. Boeckx, A. Verdoodt
Beryllium-7 (7Be) has been used as a sediment tracer to evaluate soil redistribution rates at hillslopes and as a tool to estimate sediment residence time in river systems. A key assumption for the use of 7Be as a sediment tracer is the rapid and irreversible sorption of 7Be upon contact with the soil particles. However, recent studies have raised questions about the validity of these assumptions. Seven soil types were selected to assess the adsorption rate of 7Be on the soil particles, subsequently an extraction experiment was performed to assess the rate of desorption. Next, different treatments were applied to assess the impact of soil pH, fertilizer, humic acid and organic matter on the adsorption of Be. Finally, the influence of regularly occurring cations present on the soil complex on the adsorption of Be on pure clay minerals was evaluated. The adsorption rate experiment showed a rapid and nearly complete sorption of Be for Luvisols and Cambisols under agriculture. For a temperate climate Stagnosol under forest and two highly weathered tropical Ferralsols sorption of Be was less rapid and less complete. This may result in an incomplete adsorption of 7Be on these three soils when runoff initiates, which could lead to an overestimation of erosion rates and sediment residence time. Additional observations were made during the extraction experiment, showing a significant loss of Be from the forest Stagnosol and a stable binding of Be to the arable soils. Of the different treatments applied, only pH showed to be of influence. Finally, Ca2+ and NH4+ on the soil complex had only a limited effect on the adsorption of Be, while Al3+ in combination with a low pH inhibits the adsorption of Be on the exchange complex of the pure clay minerals. All these findings more rigorously support the use of 7Be as a soil redistribution tracer in arable soils in a temperate climate at a hillslope scale. The use of 7Be in highly weathered Ferralsols or forest rich environments should be limited to avoid overestimations of erosion rates. The spatially extended use of 7Be to evaluate residence times of sediments should be avoided in catchments with rapid changing environmental parameters as they might influence the sorption behavior of 7Be.



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Kinetics of 3H, 90Sr and 137Cs content changes in hydrosphere in the Vltava River system (Czech Republic)

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Publication date: Available online 6 December 2017
Source:Journal of Environmental Radioactivity
Author(s): Eduard Hanslík, Diana Marešová, Eva Juranová, Barbora Sedlářová
The paper presents results and interpretation of long-term monitoring of occurrence and behaviour of radioisotopes 3H, 90Sr, and 137Cs in the vicinity of the Temelín Nuclear Power Plant. 3H, 90Sr, and 137Cs originate predominantly from residual contamination due to atmospheric nuclear weapons tests and the Chernobyl disaster in the last century. Monitoring of radionuclides comprised surface waters, river sediments, aquatic plants, and fish. This enables an up-to-date appraisal of the Temelín Nuclear Power Plant impact on the hydrosphere in all indicators at standard power plant operation, as well as at critical situations. The time and spatial variability of these radionuclide concentrations were monitored in the hydrosphere at in- and out-flow of the Orlík Water Reservoir. The basic evaluated radioecological characteristics can be used in assessing the long-term kinetics of decline and behaviour of radionuclides and their potential release into the environment. A very slow decline in 3H concentration at unaffected sites was observed. At sites downstream from the power plant the 3H concentrations were significantly higher, an evident impact of the power plant operation. A decline in 90Sr and 137Cs concentrations was observed in all the monitored indicators. Also, the characteristic effective and ecological half-lives were evaluated.



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Relaxivity of Ferumoxytol at 1.5 T and 3.0 T

Objectives The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Materials and Methods Ferumoxytol was diluted in gradually increasing concentrations (0.26–4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. Results A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 s−1mM−1; r1plasma = 19.0 ± 1.7 s−1mM−1; r2saline = 60.8 ± 3.8 s−1mM−1; r2plasma = 64.9 ± 1.8 s−1mM−1; r2*saline = 60.4 ± 4.7 s−1mM−1; r2*plasma = 64.4 ± 2.5 s−1mM−1; 3.0 T: r1saline = 10.0 ± 0.3 s−1mM−1; r1plasma = 9.5 ± 0.2 s−1mM−1; r2saline = 62.3 ± 3.7 s−1mM−1; r2plasma = 65.2 ± 1.8 s−1mM−1; r2*saline = 57.0 ± 4.7 s−1mM−1; r2*plasma = 55.7 ± 4.4 s−1mM−1). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Conclusions Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization. Received for publication August 25, 2017; and accepted for publication, after revision, October 23, 2017. Conflicts of interest and sources of funding: This project received R&D grant support by the Departments of Radiology and Medical Physics, University of Wisconsin, as well as the NIH (K24 DK102595). Furthermore, the authors wish to acknowledge support from GE Healthcare and Bracco Diagnostics who provide research support to the University of Wisconsin. Author contributions: S.D.S. contributed to this work while at the University of Wisconsin–Madison. S.D.S. is currently an employee of Toshiba Medical Research Institute, USA. C.N.W. contributed to this work while at the University of Wisconsin–Madison. C.N.W. is currently an employee of Synaptive Medical, Canada. T.S. contributed to this work while at the University of Wisconsin–Madison. T.S. is currently an employee at the University Hospital Basel, Switzerland. Correspondence to: Gesine Knobloch, MD, Department of Radiology, School of Medicine and Public Health, Wisconsin Institute of Medical Research, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705. E-mail: gknobloch@wisc.edu. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Age-Related Changes in Tissue Value Properties in Children: Simultaneous Quantification of Relaxation Times and Proton Density Using Synthetic Magnetic Resonance Imaging

Objectives The properties of brain tissue undergo dynamic changes during maturation. T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) are now simultaneously quantifiable within a clinically acceptable time, using a synthetic magnetic resonance imaging (MRI) sequence. This study aimed to provide age-specific reference values for T1, T2, and PD in children, using synthetic MRI. Materials and Methods We included 89 children (median age, 18 months; range, 34 weeks of gestational age to 17 years) who underwent quantitative MRI, using a multidynamic, multiecho sequence on 3 T MRI, between December 2015 and November 2016, and had no abnormal MRI/neurologic assessment findings. T1, T2, and PD were simultaneously measured in each of the 22 defined white matter and gray matter regions of interest. The measured values were plotted against age, and a curve fitting model that best explained the age dependence of tissue values was identified. Age-specific regional tissue values were calculated using a fit equation. Results The tissue values of all brain regions, except cortical PD, decreased with increasing age, and the robust negative association was best explained by modified biexponential model of the form Tissue values = T1 × exp (−C1 × age) + T2 × exp (−C2 × age). The quality of fit to the modified biexponential model was high in white matter and deep gray matter (white matter, R2 = 97%–99% [T1], 88%–95% [T2], 88%–97% [PD]; deep gray matter, R2 = 96%–97% [T1], 96% [T2], 49%–88% [PD]; cortex, 70%–83% [T1], 87%–90% [T2], 5%–27% [PD]). The white matter and deep gray matter changed the most dynamically within the first year of life. Conclusions Our study provides age-specific regional reference values, from the neonate to adolescent, of T1, T2, and PD, which could be objective tools for assessment of normal/abnormal brain development using synthetic MRI. Received for publication September 7, 2017; and accepted for publication, after revision, October 22, 2017. Conflicts of interest and sources of funding: none declared. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (http://ift.tt/2kq7jVD). Correspondence to: Young Hun Choi, MD, Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110–769, Republic of Korea. E-mail: iater@snu.ac.kr. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Bildgebung von Muskelerkrankungen



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Mitteilungen des Berufsverbandes der Deutschen Radiologen



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Table of Contents

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Publication date: January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 1





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Society Page

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Publication date: January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 1





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Information for Readers

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Publication date: January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 1





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Editorial Board

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Publication date: January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 1





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Comparison of contact radiographed and stained histological sections for osseointegration analysis of dental implants: an in vivo study

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Publication date: January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 1
Author(s): Oliver Bissinger, Carolin Götz, Anke Jeschke, Bernhard Haller, Klaus-Dietrich Wolff, Pascal Kaiser, Andreas Kolk
ObjectivesHistology is still regarded as the gold-standard to determine bone implant contact (BIC) as a parameter representing implant stability. As the further processing of cut slices for contact radiography (CR) to stained and polished histological sections is time consuming and error prone, our aim was to assess agreement between CR and Giemsa-eosin (GE) stained sections with regard to dental implants.Study DesignThreaded dental titanium implants (n = 54) from the maxillae of Goettingen minipigs were evaluated. After 28 and 56 days, BIC and the ratio of bone volume to total volume (BV/TV; 1000 μm) were determined on the same sections by using CR and GE staining, and the results were compared.ResultsModerate differences for BIC (0.6%; P = .53) and BV/TV (1.3%; P = .01) between the methods were determined, in which CR overestimated BIC and BV/TV. A strong correlation was seen between the modalities concerning BIC (28 days: r = 0.84; 56 days: r = 0.85; total: r = 0.85) and BV/TV (r = 0.96; r = 0.94; r = 0.96; all: P < .0001).ConclusionsCR enabled determination of the bone-to-implant interface in comparison with GE-stained sections. BIC and BV/TV were slightly overestimated but correlated strongly between the methods. Therefore, if BIC and BV/TV are sufficient endpoints, CR is adequate and no further preparation and staining are necessary.



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Biological significance of 5-hydroxymethylcytosine in oral epithelial dysplasia and oral squamous cell carcinoma

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Publication date: January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 1
Author(s): Maria Carolina Cuevas-Nunez, Camilla Borges F. Gomes, Sook-Bin Woo, Matthew R. Ramsey, Xiaoxin L. Chen, Shuyun Xu, Ting Xu, Qian Zhan, George F. Murphy, Christine G. Lian
ObjectivesThe aim of this study was to determine the levels of 5-hydroxylmethylcytosine (5-hmC) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) compared with those in benign, reactive inflammatory lesions and to explore whether DNA hydroxymethylation may serve as a novel biomarker for early diagnosis and prognosis of OSCC.Study DesignThe study included normal mucosa from uninvolved margins of 9 fibromas, 10 oral lichen planus, 15 OED, and 23 OSCC. Cultured human keratinocyte lines from benign oral mucosa, OED, and OSCC, as well as a murine model in which OSCC was induced with 4-nitroquinoline-1-oxide, were also evaluated.ResultsProgressive loss of 5-hmC from benign oral mucosal lesions to OED and OSCC was documented in patient samples. Decreased levels in 5-hmC that typify OED and OSCC were also detectable in human cell lines. Moreover, we characterized similar alterations in 5-hmC in an animal model of OED/OSCC.ConclusionsThis study demonstrated that 5-hmC distinguishes OED and OSCC from benign lesions with high sensitivity and specificity. Consequently, loss of 5-hmC may be useful for the diagnosis of OED with potential implications for therapy of OSCC.



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[Low dose rate brachytherapy in low and middle risk prostate cancer: Results and impact on quality of life with 5 year follow up.]

[Low dose rate brachytherapy in low and middle risk prostate cancer: Results and impact on quality of life with 5 year follow up.]

Arch Esp Urol. 2017 Dec;70(10):824-832

Authors: Balbontín F, Pizzi P, Canals A, Alliende I

Abstract
Low dose rate brachytherapy (LDR-Br) with radioactive isotopes is a curative treatment and has shown to be comparable for the management of localized prostate cancer (PCa) to more conventional treatments such as radical prostatectomy or external beam radiotherapy, but with fewer side effects. The aim of this study is to show the global, specific and biochemical recurrence-free survival in 193 patients undergoing low dose rate Brachytherapy with permanent implants with iodine 125 and analyze the quality of life impact. 193 patients with localized PCa were consecutively treated over a period of 10 years (2005-2015). All of them were followed up on levels of prostate specific antigen (PSA) and 68 of them completed a quality of life survey. The average age was 62.8 years and the average PSA was 6.4 ng/dl at the time of Br. 29.5% of patients were classified as intermediate risk, with a Gleason score sum of 7 and/or a PSA between 10 and 20 ng/dl. Mean follow-up was 64.2 months; overall, specific and biochemical recurrence-free survival were 92.8%, 99.0% and 90.2% respectively. The most significant changes in the quality of life recorded were urinary incontinence, urinary and bowel irritative symptoms, in the first 6 months after brachytherapy. Sexual function shows significant changes but all with favorable response using phosphodiesterase inhibitors. This series of patients with PCa shows similar biochemical free survival rates BFSR in low risk patients to external beam radiotherapy and radical prostatectomy, but better BFSR in intermediate risk patients. The impact in the quality of life was significant in urinary incontinence, urinary irritate symptoms, and sexual function, but they were transitory with the exception of sexual function.

PMID: 29205161 [PubMed - in process]



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Morphological observation and CBCT of the bony canal structure of the groove and the location of blood vessels and nerves in the palatine of elderly human cadavers.

Related Articles

Morphological observation and CBCT of the bony canal structure of the groove and the location of blood vessels and nerves in the palatine of elderly human cadavers.

Surg Radiol Anat. 2017 Dec 04;:

Authors: Miwa Y, Asaumi R, Kawai T, Maeda Y, Sato I

Abstract
PURPOSE: The greater and lesser palatine nerves and vessels supply the hard and soft palates, and the roots of these vessels and nerves run through a bony structure. However, the arrangement of blood vessels in the maxilla requires attention during clinical treatments, but detailed morphological information about changes in the greater and lesser palatine arteries and nerves during aging is unavailable. We therefore need detailed investigations of the morphology of the donor cadaver palatine using cone-beam computed tomography (CBCT) and macroscopic observations.
METHODS: We investigated 72 donor cadavers using macroscopic segmentation and CBCT. The results' analysis examined differences in skull measurement parameters and differences between dentate and edentulous cases.
RESULTS: The greater palatine artery and nerve showed different macroscopic arrangements in dentate and edentulous cadavers. We also classified three types of bony structures of the nerve and vessel roots in the molar regions of the palatine using CBCT images: the shallow groove, deep groove, and flat groove. The deep groove is the deepest of the three and is remarkable in edentulous elderly cadavers.
CONCLUSION: This study of macroscopic and CBCT data provides information useful for planning dental implant surgeries and autogenous bone harvesting.

PMID: 29204678 [PubMed - as supplied by publisher]



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Value of a Computer-aided Detection System Based on Chest Tomosynthesis Imaging for the Detection of Pulmonary Nodules.

Value of a Computer-aided Detection System Based on Chest Tomosynthesis Imaging for the Detection of Pulmonary Nodules.

Radiology. 2017 Dec 04;:170405

Authors: Yamada Y, Shiomi E, Hashimoto M, Abe T, Matsusako M, Saida Y, Ogawa K

Abstract
Purpose To assess the value of a computer-aided detection (CAD) system for the detection of pulmonary nodules on chest tomosynthesis images. Materials and Methods Fifty patients with and 50 without pulmonary nodules underwent both chest tomosynthesis and multidetector computed tomography (CT) on the same day. Fifteen observers (five interns and residents, five chest radiologists, and five abdominal radiologists) independently evaluated tomosynthesis images of 100 patients for the presence of pulmonary nodules in a blinded and randomized manner, first without CAD, then with the inclusion of CAD marks. Multidetector CT images served as the reference standard. Free-response receiver operating characteristic analysis was used for the statistical analysis. Results The pooled diagnostic performance of 15 observers was significantly better with CAD than without CAD (figure of merit [FOM], 0.74 vs 0.71, respectively; P = .02). The average true-positive fraction and false-positive rate per all cases with CAD were 0.56 and 0.26, respectively, whereas those without CAD were 0.47 and 0.20, respectively. Subanalysis showed that the diagnostic performance of interns and residents was significantly better with CAD than without CAD (FOM, 0.70 vs 0.62, respectively; P = .001), whereas for chest radiologists and abdominal radiologists, the FOM with CAD values were greater but not significantly: 0.80 versus 0.78 (P = .38) and 0.74 versus 0.73 (P = .65), respectively. Conclusion CAD significantly improved diagnostic performance in the detection of pulmonary nodules on chest tomosynthesis images for interns and residents, but provided minimal benefit for chest radiologists and abdominal radiologists. © RSNA, 2017 Online supplemental material is available for this article.

PMID: 29206596 [PubMed - as supplied by publisher]



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Assessment of Response to Transcatheter Arterial Chemoembolization with Doxorubicin-eluting Microspheres: Tumor Biology and Hepatocellular Carcinoma Recurrence in a 5-year Transplant Cohort.

Assessment of Response to Transcatheter Arterial Chemoembolization with Doxorubicin-eluting Microspheres: Tumor Biology and Hepatocellular Carcinoma Recurrence in a 5-year Transplant Cohort.

Radiology. 2017 Dec 04;:170731

Authors: Sandow TA, Arndt SE, Albar AA, DeVun DA, Kirsch DS, Gimenez JM, Bohorquez HE, Gilbert PJ, Thevenot PT, Nunez KG, Galliano GA, Cohen AJ, Kay D, Gulotta PM

Abstract
Purpose To assess response to transcatheter arterial chemoembolization (TACE) based on immune markers and tumor biology in patients with hepatocellular carcinoma (HCC) who were bridged to liver transplantation, and to produce an optimized pretransplantation model for posttransplantation recurrence risk. Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective analysis, 93 consecutive patients (73 male, 20 female; mean age, 59.6 years; age range, 23-72 years) underwent TACE with doxorubicin-eluting microspheres (DEB) (hereafter, DEB-TACE) and subsequently underwent transplantation over a 5-year period from July 7, 2011, to May 16, 2016. DEB-TACE response was based on modified Response Evaluation Criteria in Solid Tumors. Imaging responses and posttransplantation recurrence were compared with demographics, liver function, basic immune markers, treatment dose, and tumor morphology. Treatment response and recurrence were analyzed with uni- and multivariate statistics, as well as internal validation and propensity score matching of factors known to affect recurrence to assess independent effects of DEB-TACE response on recurrence. Results Low-grade tumors (grade 0, 1, or 2) demonstrated a favorable long-term treatment response in 87% of patients (complete response, 49%; partial response, 38%; stable disease [SD] or local disease progression [DP], 13%) versus 33% of high-grade tumors (grade 3 or 4) (complete response, 0%; partial response, 33%; SD or DP, 67%) (P < .001). Of the 93 patients who underwent treatment, 82 were followed-up after transplantation (mean duration, 757 days). Recurrence occurred in seven (9%) patients (mean time after transplantation, 635 days). Poor response to DEB-TACE (SD or DP) was present in 86% of cases and accounted for 35% of all patients with SD or DP (P < .001). By using only variables routinely available prior to liver transplantation, a validated model of posttransplantation recurrence risk was produced with a concordance statistic of 0.83. The validated model shows sensitivity of 83.6%, specificity of 82.6%, and negative predictive value of 98.4%, which are pessimistic estimates. Conclusion Response to DEB-TACE is correlated with tumor biology and patients at risk for posttransplantation recurrence, and it may be associated with HCC recurrence after liver transplantation. © RSNA, 2017 Online supplemental material is available for this article.

PMID: 29206595 [PubMed - as supplied by publisher]



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The Diagnostic Value of MR Imaging in Differentiating T Staging of Bladder Cancer: A Meta-Analysis.

The Diagnostic Value of MR Imaging in Differentiating T Staging of Bladder Cancer: A Meta-Analysis.

Radiology. 2017 Dec 04;:171028

Authors: Huang L, Kong Q, Liu Z, Wang J, Kang Z, Zhu Y

Abstract
Purpose To assess the diagnostic accuracy of magnetic resonance (MR) imaging for differentiating stage T1 or lower tumors from stage T2 or higher tumors and to analyze the influence of different imaging protocols in patients with bladder cancer. Materials and Methods A systematic literature search for original diagnostic studies was performed in PubMed, Medline, the Cochrane Library, and Web of Science. The methodologic quality of each study was evaluated by two independent reviewers who used the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data necessary to complete 2 × 2 tables were obtained, and patient, study, and imaging characteristics were extracted. Statistical analysis included data pooling, heterogeneity testing, sensitivity analyses, and forest plot construction. Results Seventeen studies (1449 patients with bladder cancer) could be analyzed. The pooled sensitivity and specificity of MR imaging were 0.90 (95% confidence interval [CI]: 0.83, 0.94) and 0.88 (95% CI: 0.77, 0.94), respectively, for differentiating tumors staged T1 or lower from those staged T2 or higher. Diffusion-weighted imaging and use of higher field strengths (3 T) improved sensitivity (0.92; 95% CI: 0.86, 0.96) and specificity (0.96; 95% CI: 0.93, 0.98). Conclusion This meta-analysis demonstrated high diagnostic performance of MR imaging for differentiating T1 or lower tumors from T2 or higher tumors in patients with bladder cancer. Higher field strength (3 T) and the use of diffusion-weighted imaging can slightly help improve sensitivity and specificity. © RSNA, 2017.

PMID: 29206594 [PubMed - as supplied by publisher]



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Glioma Grade Discrimination with MR Diffusion Kurtosis Imaging: A Meta-Analysis of Diagnostic Accuracy.

Glioma Grade Discrimination with MR Diffusion Kurtosis Imaging: A Meta-Analysis of Diagnostic Accuracy.

Radiology. 2017 Dec 04;:171315

Authors: Falk Delgado A, Nilsson M, van Westen D, Falk Delgado A

Abstract
Purpose To assess the diagnostic test accuracy and sources of heterogeneity for the discriminative potential of diffusion kurtosis imaging (DKI) to differentiate low-grade glioma (LGG) (World Health Organization [WHO] grade II) from high-grade glioma (HGG) (WHO grade III or IV). Materials and Methods The Cochrane Library, Embase, Medline, and the Web of Science Core Collection were systematically searched by two librarians. Retrieved hits were screened for inclusion and were evaluated with the revised tool for quality assessment for diagnostic accuracy studies (commonly known as QUADAS-2) by two researchers. Statistical analysis comprised a random-effects model with associated heterogeneity analysis for mean differences in mean kurtosis (MK) in patients with LGG or HGG. A bivariate restricted maximum likelihood estimation method was used to describe the summary receiver operating characteristics curve and bivariate meta-regression. Results Ten studies involving 430 patients were included. The mean difference in MK between LGG and HGG was 0.17 (95% confidence interval [CI]: 0.11, 0.22) with a z score equal to 5.86 (P < .001). The statistical heterogeneity was explained by glioma subtype, echo time, and the proportion of recurrent glioma versus primary glioma. The pooled area under the curve was 0.94 for discrimination of HGG from LGG, with 0.85 (95% CI: 0.74, 0.92) sensitivity and 0.92 (95% CI: 0.81, 0.96) specificity. Heterogeneity was driven by neuropathologic subtype and DKI technique. Conclusion MK shows high diagnostic accuracy in the discrimination of LGG from HGG. © RSNA, 2017 Online supplemental material is available for this article.

PMID: 29206593 [PubMed - as supplied by publisher]



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Head and neck Merkel cell carcinoma: a retrospective case series and critical literature review with emphasis on treatment and prognosis.

Related Articles

Head and neck Merkel cell carcinoma: a retrospective case series and critical literature review with emphasis on treatment and prognosis.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Dec 01;:

Authors: Papadiochos I, Patrikidou A, Patsatsi A, Mangoudi D, Thuau H, Vahtsevanos K

Abstract
OBJECTIVE: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with a high recurrence and mortality rates. More than half of MCCs occur in the head and neck region. This paper aims to present a retrospective case series study of primary MCCs of the head and neck treated in our department over 12 years.
STUDY DESIGN: Six patients were identified, and their characteristics, treatment modalities, and outcomes are reported. A critical review of the current literature is also included to provide up-to-date information on MCCs with special emphasis on treatment modalities and disease prognosis.
RESULTS: Management of head and neck MCCs requires early and accurate diagnosis and includes surgery, radiotherapy, and/or combination chemotherapy. Accurate cervical nodal staging is of paramount importance before establishing the definite treatment plan.
CONCLUSIONS: The results of both our case series and literature data review indicate that elective management of regional lymph nodes is recommended instead of an observation approach for patients with no identifiable disease in the lymph nodes (cN0). Because the majority of MCCs arise in the head and neck region, oral and maxillofacial surgeons are likely be the first professionals who will encounter this disease and should therefore be aware of the current diagnostic and treatment modalities.

PMID: 29203339 [PubMed - as supplied by publisher]



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AHNS Series: Do you know your guidelines? Evidence-based management of oral cavity cancers.

AHNS Series: Do you know your guidelines? Evidence-based management of oral cavity cancers.

Head Neck. 2017 Dec 05;:

Authors: Gill A, Vasan N, Givi B, Joshi A

Abstract
Oral cavity squamous cell carcinoma (OCSCC) is the most common nonmelanoma head and neck cancer in the world, with an estimated 405 000 new cases expected each year. Subsites of the oral cavity include the alveolar ridge, buccal mucosa, anterior tongue, tonsillar pillar, retromolar trigone, hard palate, gingiva, and floor of the mouth. In this issue of the AHNS "Do you know your guidelines?" series, we review the evidence-based approach to the management of oral cavity carcinomas based on the framework provided by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.

PMID: 29206324 [PubMed - as supplied by publisher]



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Factors affecting operative time in robotic thyroidectomy.

Factors affecting operative time in robotic thyroidectomy.

Head Neck. 2017 Dec 05;:

Authors: Song CM, Jang YI, Ji YB, Park JS, Kim DS, Tae K

Abstract
BACKGROUND: The purpose of this study was to evaluate factors related to operative time in robotic thyroidectomy.
METHODS: We retrospectively analyzed 240 patients who underwent robotic thyroidectomy. The total thyroidectomy cases and lobectomy cases were both categorized into those with long operative times (LOTs; upper 25% of cases) and those with short operative times (SOTs; lower 25%).
RESULTS: Among the total thyroidectomy cases, body mass index (BMI) ≥23 kg/m2 (hazard ratio [HR] 5.34; P = .008) and bilateral central neck dissection (CND; HR 14.92; P = .028) were more frequent in the LOT group in multivariate analysis. Among the lobectomy cases, BMI ≥23 kg/m2 (HR 12.92; P = .003) and unilateral CND (HR 21.38; P = .017) were the only independent risk factors for prolonged operative time.
CONCLUSION: Body habitus and clinical nodal status in the central compartment should be considered in deciding the indications for robotic thyroidectomy.

PMID: 29206321 [PubMed - as supplied by publisher]



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Volume and health outcomes: evidence from systematic reviews and from evaluation of Italian hospital data.

Volume and health outcomes: evidence from systematic reviews and from evaluation of Italian hospital data.

Epidemiol Prev. 2017 Sep-Dec;41(5-6 (Suppl 2)):1-128

Authors: Amato L, Fusco D, Acampora A, Bontempi K, Rosa AC, Colais P, Cruciani F, D'Ovidio M, Mataloni F, Minozzi S, Mitrova Z, Pinnarelli L, Saulle R, Soldati S, Sorge C, Vecchi S, Ventura M, Davoli M

Abstract
BACKGROUND Improving quality and effectiveness of healthcare is one of the priorities of health policies. Hospital or physician volume represents a measurable variable with an impact on effectiveness of healthcare. An Italian law calls for the definition of «qualitative, structural, technological, and quantitative standards of hospital care». There is a need for an evaluation of the available scientific evidence in order to identify qualitative, structural, technological, and quantitative standards of hospital care, including the volume of care above or below which the public and private hospitals may be accredited (or not) to provide specific healthcare interventions. OBJECTIVES To identify conditions/interventions for which an association between volume and outcome has been investigated. To identify conditions/interventions for which an association between volume and outcome has been proved. To analyze the distribution of Italian health providers by volume of activity. To measure the association between volume of care and outcomes of the health providers of the Italian National Health Service (NHS). METHODS Systematic review An overview of systematic reviews was performed searching PubMed, EMBASE, and The Cochrane Library up to November 2016. Studies were evaluated by 2 researchers independently; quality assessment was performed using the AMSTAR checklist. For each health condition and outcome, if available, total number of studies, participants, high volume cut-off values, and metanalysis have been reported. According to the considered outcomes, health topics were classified into 3 groups: positive association: a positive association was demonstrated in the majority of studies/participants and/or a pooled measure (metanalysis) with positive results was reported; lack of association: both studies and/or metanalysis showed no association; no sufficient evidence of association: both results of single studies and metanalysis do not allow to draw firm conclusions on the association between volume and outcome. Analysis of the distribution of Italian hospitals by volume of activity and the association between volume of activity and outcomes: the Italian National Outcome evaluation Programme 2016 The analyses were performed using the Hospital Information System and the National Tax Register (year 2015). For each condition, the number of hospitals by volume of activity was calculated. Hospitals with a volume lower than 3-5 cases/year were excluded. For conditions with more than 1,500 cases/year and frequency of outcome ≥1%, the association between volume of care and outcome was analyzed estimating risk-adjusted outcomes. RESULTS Bibliographic searches identified 80 reviews, evaluating 48 different clinical areas. The main outcome considered was intrahospital/30-day mortality. The other outcomes vary depending on the type of condition or intervention in study. The relationship between hospital volume and outcomes was considered in 47 out of 48 conditions: 34 conditions showed evidence of a positive association; • 14 conditions consider cancer surgery for bladder, breast, colon, rectum, colon rectum, oesophagus, kidney, liver, lung, ovaries, pancreas, prostate, stomach, head and neck; • 11 conditions consider cardiocerebrovascular area: nonruptured and ruptured abdominal aortic aneurysm, acute myocardial infarction, brain aneurysm, carotid endarterectomy, coronary angioplasty, coronary artery bypass, paediatric heart surgery, revascularization of lower limbs, stroke, subarachnoid haemorrhage; • 2 conditions consider orthopaedic area: knee arthroplasty, hip fracture; • 7 conditions consider other areas: AIDS, bariatric surgery, cholecystectomy, intensive care unit, neonatal intensive care unit, sepsis, and traumas; for 3 conditions, no association was demonstrated: hip arthroplasty, dialysis, and thyroidectomy. for the remaining 10 conditions, the available evidence does not allow to draw firm conclusions about the association between hospital volume and considered outcomes: surgery for testicular cancer and intracranial tumours, paediatric oncology, aortofemoral bypass, cardiac catheterization, appendectomy, colectomy, inguinal hernia, respiratory failure, and hysterectomy. The relationship between volume of clinician/surgeon and outcomes was assessed only through the literature re view; to date, it is not possible to analyze this association for Italian health provider hospitals, since information on the clinician/surgeon on the hospital discharge chart is missing. The literature found a positive association for 21 conditions: 9 consider surgery for cancer: bladder, breast, colon, colon rectum, pancreas, prostate, rectum, stomach, and head and neck; 5 consider the cardiocerebrovascular area: ruptured and nonruptured abdominal aortic aneurysm, carotid endarterectomy, paediatric heart surgery, and revascularization of the lower limbs; 2 consider the orthopaedic area: knee and hip arthroplasty; 5 consider other areas: AIDS, bariatric surgery, hysterectomy, intensive care unit, and thyroidectomy. The analysis of the distribution of Italian hospitals concerned the 34 conditions for which the systematic review has shown a positive volume-outcome association. For the following, it was possible to conduct the analysis of the association using national data: unruptured abdominal aortic aneurysm, coronary angioplasty, hip arthroplasty, knee arthroplasty, coronary artery bypass, cancer surgery (colon, liver, breast, pancreas, lung, prostate, kidney, and stomach), laparoscopic cholecystectomy, hip fracture, stroke, acute myocardial infarction. For these conditions, the association between volume and outcome of care was observed. For laparoscopic cholecystectomy and surgery of the breast and stomach cancer, the association between the volume of the discharge (o dismissal) operating unit and the outcome was analyzed. The outcomes differ depending on the condition studied. The shape of the relationship is variable among different conditions, with heterogeneous slope of the curves. DISCUSSION For many conditions, the overview of systematic reviews has shown a strong evidence of association between higher volumes and better outcomes. The quality of the available reviews can be considered good for the consistency of the results between the studies and for the strength of the association; however, this does not mean that the included studies are of good quality. Analyzing national data, potential confounders, including age and comorbidities, have been considered. The systematic review of the literature does not permit to identify predefined volume thresholds. The analysis of national data shows a strong improvement in outcomes in the first part of the curve (from very low to higher volumes) for most conditions. In some cases, the improvement in outcomes remains gradual or constant with the increasing volume of care; in other, the analysis could allow the identification of threshold values beyond which the outcome does not further improve. However, a good knowledge of the relationship between effectiveness of treatments and costs, the geographical distribution and the accessibility to healthcare services are necessary to choose the minimum volumes of care, under which specific health procedures could not been provided in the NHS. Some potential biases due to the use of information systems data should also be considered. The different way of coding among hospitals could lead to a different selection of cases for some conditions. Regarding the definition of the exposure (volume of care), a possible bias could result from misclassification of health providers with high volume of activity. Performing the intervention in different departments/ units of the same hospital would result in an overestimation of the volume of care measured for hospital rather than for department/unit. For the conditions with a further fragmentation within the same structure, the association between volumes of discharge department and outcomes has also been evaluated. In this case, the two curves were different. The limit is to attribute the outcome to the discharge unit, which in case of surgery may not be the intervention unit. A similar bias could occur if the main determinant of the outcome of treatment was the caseload of each surgeon. The results of the analysis may be biased when different operators in the same hospital/unit carried out the same procedure. In any case, the observed association between volumes and outcome is very strong, and it is unlikely to be attributable to biases of the study design. Another aspect on which there is still little evidence is the interaction between volume of the hospital and of the surgeon. A MEDICARE study suggests that in some conditions, especially for specialized surgery, the effect of the surgeon's volume of activity is different depending on the structure volume, whereas it would not differ for some less specialized surgery conditions. The data here presented still show extremely fragmented volumes of both clinical and surgical areas, with a predominance of very low volume structures. Health systems operate, by definition, in a context of limited resources, especially when the amount of resources to allocate to the health system is reduced. In such conditions, the rationalization of the organization of health services based on the volume of care may make resources available to improve the effectiveness of interventions. The identification and certification of services and providers with high volume of activity can help to reduce differences in the access to non-effective procedures. To produce additional evidence to guide the reorganization of the national healthcare system, it will be necessary to design further primary studies to evaluate the effectiveness and safety of policies aimed at concentrating interventions in structures with high volumes of activity.

PMID: 29205995 [PubMed - in process]



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HER2/HER3-positive metastatic salivary duct carcinoma in the pleural effusion: A case report.

HER2/HER3-positive metastatic salivary duct carcinoma in the pleural effusion: A case report.

Diagn Cytopathol. 2017 Dec 04;:

Authors: Murata K, Kawahara A, Ono T, Takase Y, Abe H, Naito Y, Akiba J

Abstract
Salivary duct carcinoma (SDC) is an aggressive form of salivary gland tumor, and SDC patients tend to be older men, more commonly in advanced stage with a poorer prognosis. Although the cytological characteristics of SDC on fine-needle aspiration cytology have been well-described at the primary site, they have not been explored in metastasis. Here we reported a case of HER2/HER3-positive metastatic SDC in the lung and pleural effusion. The patient was a man in his 50s who had undergone extended total parotidectomy in 2008. He was originally diagnosed as having HER2-positive left parotid SDC. Six years later a mass was discovered in the left lung by chest computed tomography (CT) and was diagnosed as metastatic SDC by both bronchial biopsy and cytology. Subsequently he had a recurrent SDC in the left pleural effusion and died of respiratory failure. Cytological findings from bronchial brushing smear showed small sheet clusters in a slightly necrotic background. In the pleural effusion cytology, tumor cells appeared as ball-like clusters of epithelioid cells with apocrine-like findings. In immunocytochemistry, HER3 of SDC cells in pleural effusion was significantly overexpressed relative to the matched primary tumor, even though HER2 amplification did not change. Cytological findings and HER family receptors differed between the primary and metastatic SDC. Therefore, molecular tests, such as protein expression and gene amplification using cytological specimens, may become important in future when determining therapy strategies in patients with distant metastasis.

PMID: 29205961 [PubMed - as supplied by publisher]



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Interobserver reliability of computed tomographic contouring of canine tonsils in radation therapy treatment planning.

Interobserver reliability of computed tomographic contouring of canine tonsils in radation therapy treatment planning.

Vet Radiol Ultrasound. 2017 Dec 04;:

Authors: Murakami K, Rancilio NJ, Plantenga JP, Moore GE, Heng HG, Lim CK

Abstract
In radiation therapy (RT) treatment planning for canine head and neck cancer, the tonsils may be included as part of the treated volume. Delineation of tonsils on computed tomography (CT) scans is difficult. Error or uncertainty in the volume and location of contoured structures may result in treatment failure. The purpose of this prospective, observer agreement study was to assess the interobserver agreement of tonsillar contouring by two groups of trained observers. Thirty dogs undergoing pre- and post-contrast CT studies of the head were included. After the pre- and postcontrast CT scans, the tonsils were identified via direct visualization, barium paste was applied bilaterally to the visible tonsils, and a third CT scan was acquired. Data from each of the three CT scans were registered in an RT treatment planning system. Two groups of observers (one veterinary radiologist and one veterinary radiation oncologist in each group) contoured bilateral tonsils by consensus, obtaining three sets of contours. Tonsil volume and location data were obtained from both groups. The contour volumes and locations were compared between groups using mixed (fixed and random effect) linear models. There was no significant difference between each group's contours in terms of three-dimensional coordinates. However there was a significant difference between each group's contours in terms of the tonsillar volume (P < 0.0001). Pre- and postcontrast CT can be used to identify the location of canine tonsils with reasonable agreement between trained observers. Discrepancy in tonsillar volume between groups of trained observers may affect RT treatment outcome.

PMID: 29205620 [PubMed - as supplied by publisher]



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EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Allergy. 2017 Sep 27;:

Authors: Pajno GB, Fernandez-Rivas M, Arasi S, Roberts G, Akdis CA, Alvaro-Lozano M, Beyer K, Bindslev-Jensen C, Burks W, Ebisawa M, Eigenmann P, Knol E, Nadeau KC, Poulsen LK, van Ree R, Santos AF, du Toit G, Dhami S, Nurmatov U, Boloh Y, Makela M, O'Mahony L, Papadopoulos N, Sackesen C, Agache I, Angier E, Halken S, Jutel M, Lau S, Pfaar O, Ryan D, Sturm G, Varga EM, van Wijk RG, Sheikh A, Muraro A, EAACI Allergen Immunotherapy Guidelines Group

Abstract
Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

PMID: 29205393 [PubMed - as supplied by publisher]



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Community development is not so new

It was refreshing to see the St Paul’s Way transformation project covered in The BMJ.1 But there are several things worth pointing out. I am in no way belittling the great work described in this...
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Use of quantitative SPECT/CT reconstruction in 99m Tc-sestamibi imaging of patients with renal masses

Abstract

Objective

Technetium-99m (99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with 99mTc-sestamibi.

Methods

Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions.

Results

The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions.

Conclusions

Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal 99mTc-sestamibi and other SPECT/CT exams. With robust quantitative image reconstruction and biomarker analysis, there may be an expanded role for SPECT/CT imaging in renal masses and other pathologic conditions.



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Use of quantitative SPECT/CT reconstruction in 99m Tc-sestamibi imaging of patients with renal masses

Abstract

Objective

Technetium-99m (99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with 99mTc-sestamibi.

Methods

Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions.

Results

The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions.

Conclusions

Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal 99mTc-sestamibi and other SPECT/CT exams. With robust quantitative image reconstruction and biomarker analysis, there may be an expanded role for SPECT/CT imaging in renal masses and other pathologic conditions.



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Disruptive technologies making cancer care more patient centred

What “disruptive” technologies could help deliver patient centred care? A recent cancer conference in London, organised by the Economist magazine, pondered this question. Examples include patient...
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health technology; +224 new citations

224 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

health technology

These pubmed results were generated on 2017/12/06

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Synthesis of Peripherally Tetrasubstituted Phthalocyanines and Their Applications in Schottky Barrier Diodes

New metal-free and metallophthalocyanine compounds (Zn, Co, Ni, and Cu) were synthesized using 2-hydroxymethyl-1,4-benzodioxan and 4-nitrophthalonitrile compounds. All newly synthesized compounds were characterized by elemental analysis, FT-IR, UV-Vis, 1H-NMR, MALDI-TOF MS, and GC-MS techniques. The applications of synthesized compounds in Schottky barrier diodes were investigated. Ag/Pc/p–Si structures were fabricated and charge transport mechanism in these devices was investigated using dc technique. It was observed from the analysis of the experimental results that the charge transport can be described by Ohmic conduction at low values of the reverse bias. On the other hand, the voltage dependence of the measured current for high values of the applied reverse bias indicated that space charge limited conduction is the dominant mechanism responsible for dc conduction. From the observed voltage dependence of the current density under forward bias conditions, it has been concluded that the charge transport is dominated by Poole-Frenkel emission.

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Risk Factors for Chemotherapy-Related Toxicity and Adverse Events in Elderly Thai Cancer Patients: A Prospective Study

Objectives: To assess factors predisposing to severe chemotherapy-related toxicity and adverse events (AEs) and dose modification in aging cancer patients. Methods: Cancer patients aged ≥70 years scheduled to receive the first cycle of a new chemotherapy regimen were enrolled. On the day of starting chemotherapy, demographic data, performance status (PS), and geriatric parameters were recorded. AEs and chemotherapy modification were recorded. Quality of life (QOL) was assessed at baseline and 3 months after starting chemotherapy or at the end of chemotherapy. Results: We included 151 patients (mean age, 76.4 years) with gastrointestinal (47%), lung (24%), breast (9%), or genitourinary (6%) cancer. All-grade and severe AEs occurred in 83 and 42% of patients, respectively; 51.6% of patients required chemotherapy modification due to toxicities. A higher incidence of severe AEs (71% vs. 39%, p = 0.01) and poorer QOL was found in patients with PS 2 than in those with PS 0-1. Patients with PS 2 or who received palliative-intent chemotherapy or had multiple comorbidities were more likely to discontinue chemotherapy because of toxicity. Conclusions: PS remains a key predictor of chemotherapy-related toxicity in elderly patients. PS 2 was correlated with higher incidence of severe AEs, premature treatment discontinuation, and worsening QOL after treatment.
Oncology

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Pharmacological profile of mephedrone analogs and related new psychoactive substances

Mephedrone is a synthetic cathinone and one of the most popular recreationally used new psychoactive substances. The aim of the present study was to characterize the in vitro pharmacology of novel analogs of mephedrone and related newly emerged designer stimulants.; We determined norepinephrine, dopamine, and serotonin transporter inhibition potencies and monoamine release in transporter-transfected human embryonic kidney 293 cells. We also assessed monoamine receptor and transporter binding affinities.; Mephedrone analogs potently inhibited the norepinephrine transporter and, with the exception of 3-methylmethcathinone (3-MMC), inhibited the serotonin transporter more potently than the dopamine transporter. Similar to classic amphetamines, mephedrone analogs were substrate-type monoamine releasers. 5-(2-Aminopropyl)indole (5-IT) was a highly potent monoamine transporter inhibitor and a releaser of dopamine and serotonin. 4-Methylamphetamine (4-MA) mediated efflux of all three monoamines and inhibited the serotonin transporter more potently than the dopamine transporter, unlike amphetamine. N-methyl-2-aminoindane (N-methyl-2-AI) was a selective norepinephrine transporter inhibitor and norepinephrine releaser, whereas 5-methoxy-6-methyl-2-aminoindane (MMAI) was a selective serotonin transporter inhibitor and serotonin releaser. All of the drugs interacted with monoamine receptors.; The predominant actions on serotonin vs. dopamine transporters suggest that dimethylmethcathinones, 4-MA, and MMAI cause entactogenic effects similar to 3,4-methylenedioxymethamphetamine, whereas 3-MMC, 5-IT, and N-methyl-2-AI have more stimulant-type properties like amphetamine. Because of pharmacological and structural similarity to mephedrone, similar health risks can be expected for these analogs.

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Brexit is shifting drug industry’s focus away from UK, MPs hear

Drug companies seem to be looking to base future operations and processes outside the UK because of uncertainty caused by Brexit, MPs have been told.During an evidence session of the parliamentary...
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IJMS, Vol. 18, Pages 2640: An Updated View of Translocator Protein (TSPO)

IJMS, Vol. 18, Pages 2640: An Updated View of Translocator Protein (TSPO)

International Journal of Molecular Sciences doi: 10.3390/ijms18122640

Authors: Nunzio Denora Giovanni Natile

Decades of study on the role of mitochondria in living cells have evidenced the importance of the 18 kDa mitochondrial translocator protein (TSPO), first discovered in the 1977 as an alternative binding site for the benzodiazepine diazepam in the kidneys. This protein participates in a variety of cellular functions, including cholesterol transport, steroid hormone synthesis, mitochondrial respiration, permeability transition pore opening, apoptosis, and cell proliferation. Thus, TSPO has become an extremely attractive subcellular target for the early detection of disease states that involve the overexpression of this protein and the selective mitochondrial drug delivery. This special issue was programmed with the aim of summarizing the latest findings about the role of TSPO in eukaryotic cells and as a potential subcellular target of diagnostics or therapeutics. A total of 9 papers have been accepted for publication in this issue, in particular, 2 reviews and 7 primary data manuscripts, overall describing the main advances in this field.



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IJMS, Vol. 18, Pages 2639: Expression Profiling of Autophagy Genes BxATG1 and BxATG8 under Biotic and Abiotic Stresses in Pine Wood Nematode Bursaphelenchus xylophilus

IJMS, Vol. 18, Pages 2639: Expression Profiling of Autophagy Genes BxATG1 and BxATG8 under Biotic and Abiotic Stresses in Pine Wood Nematode Bursaphelenchus xylophilus

International Journal of Molecular Sciences doi: 10.3390/ijms18122639

Authors: Fan Wu Li-Na Deng Xiao-Qin Wu Hong-Bin Liu Jian-Ren Ye

The pine wood nematode (PWN), Bursaphelenchus xylophilus, is the pathogen of pine wilt disease (PWD) and causes huge economic losses in pine forests and shows a remarkable ability to survive under unfavorable and changing environmental conditions. This ability may be related to autophagy, which is still poorly understood in B. xylophilus. Our previous studies showed that autophagy exists in PWN. Therefore, we tested the effects of autophagy inducer rapamycin on PWN and the results revealed that the feeding rate and reproduction were significantly promoted on fungal mats. The gene expression patterns of BxATG1 and BxATG8 under the different stress were determined by quantitative reverse transcription PCR (qRT-PCR). We tested the effects of RNA interference on BxATG1 and BxATG8 in PWN during different periods of infection in Pinus thunbergii. The results revealed that BxATG1 and BxATG8 may play roles in allowing PWN to adapt to changing environmental conditions and the virulence of PWN was influenced by the silence of autophagy-related genes BxATG1 and BxATG8. These results provided fundamental information on the relationship between autophagy and PWN, and on better understanding of gene function of BxATG1 and BxATG8 in PWN.



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IJMS, Vol. 18, Pages 2637: Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2, and Cytokine Production of Mouse and Human Macrophages Are Suppressed by Pheophytin-b

IJMS, Vol. 18, Pages 2637: Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2, and Cytokine Production of Mouse and Human Macrophages Are Suppressed by Pheophytin-b

International Journal of Molecular Sciences doi: 10.3390/ijms18122637

Authors: Chun-Yu Lin Wen-Hung Wang Shin-Huei Chen Yu-Wei Chang Ling-Chien Hung Chung-Yi Chen Yen-Hsu Chen

Sepsis is an overwhelming systemic response to infection that frequently results in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine overproduction are thought to be associated with the immunostimulatory cascade in sepsis. In the present study, we analyzed the anti-inflammatory efficacy of the pheophytin-b on both RAW 264.7 murine macrophage and purified human CD14+ monocytes stimulated with lipopolysaccharide (LPS) and elucidated the mechanisms by analyzing the cell signaling pathways known to be activated in sepsis. Pheophytin-b suppressed the overexpression of NO, PGE2, and cytokines in LPS-stimulated macrophages without inducing cytotoxicity. It also reduced NOS2 and COX-2 mRNA and protein levels. The inhibitory effects on NO, PGE2, and cytokine overproduction arose from the suppression of STAT-1 and PI3K/Akt pathways; no changes in NF-κB, MAPK, and AP-1 signaling were detected. Thus, pheophytin-b may represent a potential candidate to beneficially modulate the inflammatory response in sepsis.



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IJMS, Vol. 18, Pages 2631: Pan-Domain Analysis of ZIP Zinc Transporters

IJMS, Vol. 18, Pages 2631: Pan-Domain Analysis of ZIP Zinc Transporters

International Journal of Molecular Sciences doi: 10.3390/ijms18122631

Authors: Laura Lehtovirta-Morley Mohammad Alsarraf Duncan Wilson

The ZIP (Zrt/Irt-like protein) family of zinc transporters is found in all three domains of life. However, little is known about the phylogenetic relationship amongst ZIP transporters, their distribution, or their origin. Here we employed phylogenetic analysis to explore the evolution of ZIP transporters, with a focus on the major human fungal pathogen, Candida albicans. Pan-domain analysis of bacterial, archaeal, fungal, and human proteins revealed a complex relationship amongst the ZIP family members. Here we report (i) a eukaryote-wide group of cellular zinc importers, (ii) a fungal-specific group of zinc importers having genetic association with the fungal zincophore, and, (iii) a pan-kingdom supercluster made up of two distinct subgroups with orthologues in bacterial, archaeal, and eukaryotic phyla.



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IJMS, Vol. 18, Pages 2636: Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P1 Receptor Modulator in Healthy Subjects

IJMS, Vol. 18, Pages 2636: Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P1 Receptor Modulator in Healthy Subjects

International Journal of Molecular Sciences doi: 10.3390/ijms18122636

Authors: Pierre-Eric Juif Daniela Baldoni Maribel Reyes Darren Wilbraham Salvatore Febbraro Andrea Vaclavkova Matthias Hoch Jasper Dingemanse

The pharmacokinetics, pharmacodynamics, tolerability, and food effect of cenerimod, a potent sphingosine-1-phosphate subtype 1 receptor modulator, were investigated in three sub-studies. Two double-blind, placebo-controlled, randomised studies in healthy male subjects were performed. Cenerimod was administered either as single dose (1, 3, 10 or 25 mg; Study 1) or once daily for 35 days (0.5, 1, 2 or 4 mg; Study 2). A two-period cross-over, open-label study was performed to assess the food effect (1 mg, Study 3). The pharmacokinetic profile of cenerimod was characterised by a tmax of 5.0–6.2 h. Terminal half-life after single and multiple doses ranged from 170 to 199 h and 283 to 539 h, respectively. Food had no relevant effect on the pharmacokinetics of cenerimod. A dose-dependent decrease in lymphocyte count was observed after initiation of cenerimod and reached a plateau (maximum change from baseline: −64%) after 20–23 days of treatment. Lymphocyte counts returned to baseline values at end-of-study examination. One serious adverse event of circulatory collapse (25 mg dose group, maximum tolerated dose: 10 mg) and adverse events of mild-to-moderate intensity were reported. Treatment initiation was associated with transient decreases in heart rate and blood pressure at doses &gt;1 and ≥10 mg, respectively.



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Comparative Analyses of Transport Proteins Encoded within the Genomes of Bdellovibrio bacteriovorus HD100 and Bdellovibrio exovorus JSS

228391?imgType=4

Bdellovibrio, δ-proteobacteria, including B. bacteriovorus (Bba) and B. exovorus (Bex), are obligate predators of other Gram-negative bacteria. While Bba grows in the periplasm of the prey cell, Bex grows externally. We have analyzed and compared the transport proteins of these 2 organisms based on the current contents of the Transporter Classification Database (TCDB; www.tcdb.org). Bba has 103 transporters more than Bex, 50% more secondary carriers, and 3 times as many MFS carriers. Bba has far more metabolite transporters than Bex as expected from its larger genome, but there are 2 times more carbohydrate uptake and drug efflux systems, and 3 times more lipid transporters. Bba also has polyamine and carboxylate transporters lacking in Bex. Bba has more than twice as many members of the Mot-Exb family of energizers, but both may have energizers for gliding motility. They use entirely different types of systems for iron acquisition. Both contain unexpectedly large numbers of pseudogenes and incomplete systems, suggesting that they are undergoing genome size reduction. Interestingly, all 5 outer-membrane receptors in Bba are lacking in Bex. The 2 organisms have similar numbers and types of peptide and amino acid uptake systems as well as protein and carbohydrate secretion systems. The differences observed correlate with and may account, in part, for the different lifestyles of these 2 bacterial predators.
J Mol Microbiol Biotechnol 2017;27:332-349

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Echinochrome A Release by Red Spherule Cells Is an Iron-Withholding Strategy of Sea Urchin Innate Immunity

Cellular immune defences in sea urchins are shared amongst the coelomocytes - a heterogeneous population of cells residing in the coelomic fluid (blood equivalent) and tissues. The most iconic coelomocyte morphotype is the red spherule cell (or amebocyte), so named due to the abundance of cytoplasmic vesicles containing the naphthoquinone pigment echinochrome A. Despite their identification over a century ago, and evidence of antiseptic properties, little progress has been made in characterising the immunocompetence of these cells. Upon exposure of red spherule cells from sea urchins, i.e., Paracentrotus lividus and Psammechinus miliaris, to microbial ligands, intact microbes, and damage signals, we observed cellular degranulation and increased detection of cell-free echinochrome in the coelomic fluid ex vivo. Treatment of the cells with ionomycin, a calcium-specific ionophore, confirmed that an increase in intracellular levels of Ca2+ is a trigger of echinochrome release. Incubating Gram-positive/negative bacteria as well as yeast with lysates of red spherule cells led to significant reductions in colony-forming units. Such antimicrobial properties were counteracted by the addition of ferric iron (Fe3+), suggesting that echinochrome acts as a primitive iron chelator in echinoid biological defences.
J Innate Immun

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Squamous cell carcinoma of unknown primary of the head and neck: Favorable prognostic factors comparable to those in oropharyngeal cancer

Abstract

Background

Treatment for squamous cell carcinoma (SCC) of unknown primary consists of radiotherapy (RT) +/- chemotherapy or neck dissection +/- adjuvant RT/chemoradiotherapy (CRT). We compared these strategies and identified prognostic factors.

Methods

From 1993 to 2015, 75 patients with SCC of unknown primary had RT-based or surgery-based treatment. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Event-time distributions were estimated using the Kaplan-Meier method.

Results

Five-year OS and DFS for RT-based and surgery-based treatments were similar (OS 73% vs 68%, respectively; DFS 65% vs 64%, respectively). Among 38 patients with p16 data, 76% were p16 positive and showed improved 5-year DFS (90% vs 33%; P = .001) and OS (96% vs 33%; P < .001). Smoking history ≤10 pack-years conferred better 5-year DFS (88% vs 49%; P < .001) and OS (91% vs 59%; P < .001).

Conclusion

RT-based and surgery-based treatments produced similar outcomes. Patients with p16-positive disease with ≤10 pack-years of smoking history and limited nodal stage constitute a “low-risk” group in SCC of unknown primary similar to that in oropharyngeal cancer.



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