Παρασκευή 16 Φεβρουαρίου 2018

GEC-ESTRO ACROP recommendations in skin brachytherapy

Publication date: Available online 16 February 2018
Source:Radiotherapy and Oncology
Author(s): Jose L. Guinot, Agata Rembielak, Jose Perez-Calatayud, Silvia Rodríguez-Villalba, Janusz Skowronek, Luca Tagliaferri, Benjamin Guix, Victor Gonzalez-Perez, Vincenzo Valentini, György Kovacs
PurposeThe aim of this publication is to compile available literature data and expert experience regarding skin brachytherapy (BT) in order to produce general recommendations on behalf of the GEC-ESTRO Group.MethodsWe have done an exhaustive review of published articles to look for general recommendations.ResultsRandomized controlled trials, systemic reviews and meta-analysis are lacking in literature and there is wide variety of prescription techniques successfully used across the radiotherapy centers. BT can be delivered as superficial application (also called contact BT or plesiotherapy) or as interstitial for tumours thicker than 5 mm within any surface, including very irregular. In selected cases, particularly in tumours located within curved surfaces, BT can be advantageous modality from dosimetric and planning point of view when compared to external beam radiotherapy. The general rule in skin BT is that the smaller the target volume, the highest dose per fraction and the shortest overall length of treatment can be used.ConclusionSkin cancer incidence is rising worldwide. BT offers an effective non-invasive or minimally invasive and relative short treatment that particularly appeals to elder and frail population.



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A statistical comparison of motion mitigation performances and robustness of various pencil beam scanned proton systems for liver tumour treatments

Publication date: Available online 16 February 2018
Source:Radiotherapy and Oncology
Author(s): Ye Zhang, Isabel Huth, Damien Charles Weber, Antony John Lomax
Background and purposeDifferent scanned proton therapy systems provide different scanning scenarios, directly changing the temporal interference between sequential beam delivery and tumour motion. We aim here to quantify the interplay effects and compare motion mitigation performance among different PBS scanning systems.Materials and methodsUsing 6 4DCT(MRI) datasets of liver tumours with irregular motions greater than 10 mm, 4D treatments with single- and double-field plans, and assuming various doses and motion mitigation approaches, were simulated for 8 PBS scenarios including spot or raster scanning, layered or volumetric rescanning, gating, constant or varying beam current and cyclotron or synchrotron beam sources. The resulting 4D plans were compared using the homogeneity index (D5-D95 in CTV) and treatment time.ResultsIndependent of scanning scenario and field dose, neither gating nor rescanning alone could mitigate motion effects completely. Re-gating (rescanning with gating) however was found to be similarly effective for all scanning scenarios, most field doses and both rescan modes, with the difference being mainly in the treatment efficiency. The advantage of cyclotron-based systems together with layer-by-layer beam current variation was demonstrated by the nearly constant treatment time as a function of increased field dose.ConclusionIndependently of PBS scanning dynamics, re-gating is sufficient to achieve acceptable 4D plan quality close to those of the static references.



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Dose–response curves for MRI-detected radiation-induced temporal lobe reactions in patients after proton and carbon ion therapy: Does the same RBE-weighted dose lead to the same biological effect?

To derive the dose–response curve for temporal lobe reactions (TLRs) after proton therapy and to compare the resulting relative biological effectiveness (RBE)-weighted tolerance doses based on an RBE of 1.1 with published values for carbon ions, which were calculated by the two versions of the local effect model (LEM I or IV).

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A statistical comparison of motion mitigation performances and robustness of various pencil beam scanned proton systems for liver tumour treatments

Different scanned proton therapy systems provide different scanning scenarios, directly changing the temporal interference between sequential beam delivery and tumour motion. We aim here to quantify the interplay effects and compare motion mitigation performance among different PBS scanning systems.

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Significant reduction in indoor radon in newly built houses

Publication date: Available online 16 February 2018
Source:Journal of Environmental Radioactivity
Author(s): Ingvild E. Finne, Trine Kolstad, Maria Larsson, Bård Olsen, Josephine Prendergast, Anne Liv Rudjord
Results from two national surveys of radon in newly built homes in Norway, performed in 2008 and 2016, were used in this study to investigate the effect of the 2010 building regulations introducing limit values on radon and requirements for radon prevention measures upon construction of new buildings.In both surveys, homes were randomly selected from the National Building Registry. The overall result was a considerable reduction of radon concentrations after the implementation of new regulations, but the results varied between the different dwelling categories. A statistically significant reduction was found for detached houses where the average radon concentration was almost halved from 76 to 40 Bq/m3. The fraction of detached houses which had at least one frequently occupied room with a radon concentration above the Action Level (100 Bq/m3) fell from 23.9% to 6.4%, while the fraction above the Upper Limit Value (200 Bq/m3) was reduced from 7.6% to 2.5%. In 2008 the average radon concentration measured in terraced and semi-detached houses was 44 and in 2016 it was 29 Bq/m3, but the reduction was not statistically significant. For multifamily houses, it was not possible to draw a conclusion due to insufficient number of measurements.



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Novel spectrometers for environmental dose rate monitoring

Publication date: Available online 16 February 2018
Source:Journal of Environmental Radioactivity
Author(s): P. Kessler, B. Behnke, R. Dabrowski, H. Dombrowski, A. Röttger, S. Neumaier
A new generation of dosemeters, based on the scintillators LaBr3, CeBr3 and SrI2, read out with conventional photomultipliers, to be used in the field of environmental gamma-radiation monitoring, was investigated. The main features of these new instruments and especially their outdoor performance, studied by long-term investigations under real weather conditions, are presented. The systems were tested at the reference sites for environmental radiation of the Physikalisch-Technische Bundesanstalt. The measurements are compared with that of well characterized classical dose rate reference instruments to demonstrate the suitability of new spectrometers for environmental dose rate monitoring even in adverse weather conditions. Their potential to replace the (mainly Geiger Müller based) dose rate meters operated in about 5000 European early waning network stations as well as in environmental radiation monitoring in general is shown.



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A brief overview of decommissioning and environmental remediation over the last 20 years

Publication date: Available online 16 February 2018
Source:Journal of Environmental Radioactivity
Author(s): Monken-Fernandes Horst, Michal Vladimir




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Long-term outcomes of Universiti Kebangsaan Malaysia Cochlear Implant Program among pediatric implantees.

Long-term outcomes of Universiti Kebangsaan Malaysia Cochlear Implant Program among pediatric implantees.

Int J Pediatr Otorhinolaryngol. 2018 Feb;105:27-32

Authors: Goh BS, Fadzilah N, Abdullah A, Othman BF, Umat C

Abstract
OBJECTIVES: Cochlear implant (CI) greatly enhances auditory performance as compared to hearing aids and has dramatically affected the educational and communication outcomes for profoundly deaf children. Universiti Kebangsaan Malaysia (UKM) pioneered CI program in 1995 in the South East Asia. We would like to report the long-term outcomes of UKM paediatric cochlear implantation in terms of: the proportion of children who were implanted and still using the device, the children's modes of communication, their educational placements, and their functional auditory/oral performance. We also examined the factors that affected the outcomes measured.
STUDY DESIGN: This was a cross sectional observational study.
METHODS: Two sets of questionnaires were given to 126 parents or primary caregivers of the implantees. The first set of questionnaire contained questions to assess the children's usage of CI, their types of education placement, and their modes of communication. The second set of questionnaire was the Parent's Evaluation Of Aural/Oral Performance of Children (PEACH) to evaluate the children's auditory functionality.
RESULTS: Our study showed that among the implantees, 97.6% are still using their CI, 69.8% communicating orally, and 58.5% attending mainstream education. For implantees that use oral communication and attend mainstream education, their mean age of implantation is 38 months. This is significantly lower compared to the mean age of implantation of implantees that use non-oral communication and attend non-mainstream education. Simple logistic regression analysis shows age of implantation reliably predicts implantees (N = 126) would communicate using oral communication with odds ratio of 0.974, and also predict mainstream education (N = 118) with odds ratio of 0.967. The median score of PEACH rating scale is 87.5% in quiet, and this significantly correlates with an earlier age of implantation (r = -0.235 p = 0.048).
CONCLUSIONS: UKM Cochlear Implant Program has achieved reasonable success among the pediatric implantees, with better outcomes seen in those implanted at the age of less than 4 years old.

PMID: 29447813 [PubMed - in process]



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Difficult airway intubation simulation using Bonfils fiberscope and rigid fiberscope for surgical training.

Difficult airway intubation simulation using Bonfils fiberscope and rigid fiberscope for surgical training.

Int J Pediatr Otorhinolaryngol. 2018 Feb;105:171-175

Authors: Dharmarajan H, Liu YC, Hippard HK, Chandy B

Abstract
INTRODUCTION: Pediatric otolaryngologists are frequently called to assist in difficult airway management in newborns with Pierre Robin Sequence (PRS) who have microretrognathia, glossoptosis, and an anterior larynx. The Bonfils fiberscope (BF) is a curved rigid scope designed to provide superior visualization in the anterior larynx.
OBJECTIVE: (1) to assess whether BF provides an improvement in intubation success rate, time to intubation, or airway visualization as compared to rigid fiberscope (RF) in a difficult airway simulation setting and (2) to determine whether a training program for BF can improve time to intubation through practice trials.
METHODS: Six right-handed trainees completed five trials on each of the three following airway models using the BF and RF: normal anatomy, anterior larynx and PRS. The normal larynx model was intubated only with RF. Main outcome measures were the time needed for tracheal intubation and Cormack-Lehane classification (1-4).
RESULTS: The majority of the intubation trials showed a statistically significant difference between first and last completion times (p < .05) suggesting construct validity. Only the anterior larynx trials with BF did not demonstrate an improvement in time to intubation between first and last attempts (p < .3125). For the PRS retrognathia model, there was no statistically significant difference in time to intubation between using the BF and the RF (p < .44); in the anterior larynx model, the RF yielded a faster time to intubation than the BF on the final trial attempts (p < .0313). By Cormack-Lehane classification measures, laryngeal visualization by the BF was better than RF in the PRS manikin (p < .0022) while there was no significant difference in grade scores for the anterior larynx manikin (p < .45). All six trainees reported an improved visualization of the larynx with the BF compared to the RF for both the anterior larynx and PRS manikins; at the end of the trial runs, all participants noted an improvement in comfort level using the BF.
CONCLUSION: The difficult airway simulation model is feasible for surgical training. BF adds superior visualization of the anterior larynx in PRS. Otolaryngology training programs may include BF as a supplemental tool in addition to RF as a part of the airway equipment training since there is significant improvement in time to intubation with consecutive practice trials and superior laryngeal visualization.

PMID: 29447809 [PubMed - in process]



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Sialoendoscopy for treatment of juvenile recurrent parotitis: The Brescia experience.

Sialoendoscopy for treatment of juvenile recurrent parotitis: The Brescia experience.

Int J Pediatr Otorhinolaryngol. 2018 Feb;105:163-166

Authors: Berlucchi M, Rampinelli V, Ferrari M, Grazioli P, Redaelli De Zinis LO

Abstract
OBJECTIVE: To evaluate the role of sialoendoscopy associated with steroid irrigation for juvenile recurrent parotitis (JRP) at a tertiary referral hospital.
METHODS: Clinical records of patients affected by JRP and treated with operative sialoendoscopy between June 2011 and April 2017 were retrospectively reviewed. Data on demographics, number of acute episodes per year before and after surgery, characteristics of the surgical procedure, hospitalization time, and rate of complications were collected. The outcome of the procedure was measured by comparing the number of episodes of parotid swelling before and after salivary endoscopic treatment.
RESULTS: Twenty-three patients for a total of 34 operative sialoendoscopies were included in the study. Before the surgical endoscopic procedure, the mean number of parotid swelling was 10 episodes per year. At sialoendoscopy, typical endoscopic findings such as mucous plugs, stenosis of the duct, intraductal debris, and pale ductal appearance were evident. All patients were discharged on the first postoperative day. A significant decrease in the number of swelling episodes per year was observed compared to the preoperative rate (p = .0004). Complete resolution of the disorder was obtained in 35% of patients.
CONCLUSIONS: Operative sialoendoscopy with steroid irrigation can be considered a valid therapeutic treatment for JRP. The technique is conservative, effective, safe, and, potentially repeatable. Short hospitalization time, rapid recovery, absence of peri-operative complications, and a high rate of good outcomes are the main advantages of this treatment.

PMID: 29447807 [PubMed - in process]



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A clinical pathway for the postoperative management of hypocalcemia after pediatric thyroidectomy reduces blood draws.

A clinical pathway for the postoperative management of hypocalcemia after pediatric thyroidectomy reduces blood draws.

Int J Pediatr Otorhinolaryngol. 2018 Feb;105:132-137

Authors: Patel NA, Bly RA, Adams S, Carlin K, Parikh SR, Dahl JP, Manning S

Abstract
OBJECTIVES: Postoperative calcium management is challenging following pediatric thyroidectomy given potential limitations in self-reporting symptoms and compliance with phlebotomy. A protocol was created at our tertiary children's institution utilizing intraoperative parathyroid hormone (PTH) levels to guide electrolyte management during hospitalization. The objective of this study was to determine the effect of a new thyroidectomy postoperative management protocol on two primary outcomes: (1) the number of postoperative calcium blood draws and (2) the length of hospital stay.
STUDY DESIGN: Institutional review board approved retrospective study (2010-2016).
METHODS: Consecutive pediatric total thyroidectomy and completion thyroidectomy ± neck dissection cases from 1/1/2010 through 8/5/2016 at a single tertiary children's institution were retrospectively reviewed before and after initiation of a new management protocol. All cases after 2/1/2014 comprised the experimental group (post-protocol implementation). The pre-protocol control group consisted of cases prior to 2/1/2014. Multivariable linear and Poisson regression models were used to compare the control and experimental groups for outcome measure of number of calcium lab draws and hospital length of stay.
RESULTS: 53 patients were included (n = 23, control group; n = 30 experimental group). The median age was 15 years. 41 patients (77.4%) were female. Postoperative calcium draws decreased from a mean of 5.2 to 3.6 per day post-protocol implementation (Rate Ratio = 0.70, p < .001), adjusting for covariates. The mean number of total inpatient calcium draws before protocol initiation was 13.3 (±13.20) compared to 7.2 (±4.25) in the post-protocol implementation group. Length of stay was 2.1 days in the control group and 1.8 days post-protocol implementation (p = .29). Patients who underwent concurrent neck dissection had a longer mean length of stay of 2.32 days compared to 1.66 days in those patients who did not undergo a neck dissection (p = .02). Hypocalcemia was also associated with a longer mean length of stay of 2.41 days compared to 1.60 days in patients who did not develop hypocalcemia (p < .01).
CONCLUSIONS: The number of calcium blood draws was significantly reduced after introduction of a standardized protocol based on intraoperative PTH levels. The hospital length of stay did not change. Adoption of a standardized postoperative protocol based on intraoperative PTH levels may reduce the number of blood draws in children undergoing thyroidectomy.

PMID: 29447801 [PubMed - in process]



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Papillary thyroid carcinoma presenting as acute suppurative thyroiditis: A case report and review of the literature.

Papillary thyroid carcinoma presenting as acute suppurative thyroiditis: A case report and review of the literature.

Int J Pediatr Otorhinolaryngol. 2018 Feb;105:12-15

Authors: Kalladi Puthanpurayil S, Francis GL, Kraft AO, Prasad U, Petersson RS

Abstract
Acute suppurative thyroiditis is a rare, potentially life-threatening condition. We report the case of a 17-year-old male who initially presented with a thyroid abscess. Due to persistent symptoms and lack of evidence for underlying predisposing factors, he was followed closely and subsequently diagnosed with papillary thyroid cancer. He was successfully managed with surgery. His clinical course, radiological evaluation, and pathology reports are presented here along with a review of the literature. This case of papillary thyroid cancer highlights the need for close follow-up of patients presenting with a thyroid abscess, when other predisposing risk factors are not evident.

PMID: 29447798 [PubMed - in process]



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Endoscopic transpterygoid approach to a mass in a child.

Endoscopic transpterygoid approach to a mass in a child.

Int J Pediatr Otorhinolaryngol. 2018 Feb;105:115-117

Authors: Lee DH, Baek HJ, Yoon TM, Lee JK, Lim SC

Abstract
The endoscopic transterygoid approach to the petrous apex is a feasible/alternative approach in carefully selected patients with specific favorable anatomy, even children. This approach, unlike traditional approaches, spares cochlear and vestibular function. We report a case of a six-year-old boy with embryonal rhabdomyosarcoma of the petrous apex that was diagnosed via the endoscopic transpterygoid approach.

PMID: 29447796 [PubMed - in process]



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Laryngeal squamous cell papilloma is highly associated with human papillomavirus.

Laryngeal squamous cell papilloma is highly associated with human papillomavirus.

Jpn J Clin Oncol. 2018 Feb 13;:

Authors: Orita Y, Gion Y, Tachibana T, Ikegami K, Marunaka H, Makihara S, Yamashita Y, Miki K, Makino T, Akisada N, Akagi Y, Kimura M, Yoshino T, Nishizaki K, Sato Y

Abstract
Objective: To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection.
Methods: Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16INK4a antibody.
Results: In 21 cases (61.8%) with laryngeal squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%) were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11 (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients (<60 years) showed a higher rate of HPV infection than older patients. Among the 34 cases with laryngeal papilloma, no malignant transformation was observed during the study period. With IHC staining, positive expression of p16 was observed in 20 cases (58.8%). HPV infection and p16-expression were associated with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV-positivity in the oral cavity, and none of the 15 oropharyngeal cases were positive for HPV, and none of the oral cavity and oropharyngeal cases showed koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly correlated each other.
Conclusions: HPV infection is frequently associated with laryngeal squamous cell papilloma, and koilocytosis is a characteristic pathological finding. To the best of our knowledge, this is the first report which have described infections with multiple HPV types in laryngeal papilloma.

PMID: 29447361 [PubMed - as supplied by publisher]



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Image Quality on Dual-energy CTPA Virtual Monoenergetic Images

Publication date: Available online 15 February 2018
Source:Academic Radiology
Author(s): Bari Dane, Hersh Patel, Thomas O'Donnell, Francis Girvin, Geraldine Brusca-Augello, Jeffrey B. Alpert, Bowen Niu, Mariam Attia, James Babb, Jane P. Ko
Rationale and ObjectivesThis study aims to determine the optimal photon energy for image quality of the pulmonary arteries (PAs) on dual-energy computed tomography (CT) pulmonary angiography (CTPA) utilizing low volumes of iodinated contrast.Materials and MethodsThe study received institutional review board exemption and was Health Insurance Portability and Accountability Act compliant. Adults (n = 56) who underwent dual-energy CTPA with 50–60 cc of iodinated contrast on a third-generation dual-source multidetector CT were retrospectively and consecutively identified. Twelve virtual monoenergetic kiloelectron volt (keV) image data sets (40–150 keV, 10-keV increments) were generated with a second-generation noise-reducing algorithm. Standard regions of interest were placed on main, right, left, and right interlobar pulmonary arteries; pectoralis muscle; and extrathoracic air. Attenuation [mean CT number (Hounsfield unit, HU)], noise [standard deviation (HU)], signal to noise (SNR), and contrast to noise ratio were evaluated. Three blinded chest radiologists rated (from 1 to 5, with 5 being the best) randomized monoenergetic and weighted-average images for attenuation and noise. P < .05 was considered significant.ResultsRegion of interest mean CT number increased as keV decreased, with 40 keV having the highest value (P < .001). Mean SNR was highest for 40–60 keV (P < .05) (14.5–14.7) and was higher (P < .05) than all remaining energies (90–150 keV) for all vessel regions combined. Contrast to noise ratio was highest for 40 keV (P < .001) and decreased as keV increased. SNR was highest at 60 and 70 keV, only slightly higher than 40–50 keV (P < .05). Reader scores for 40–50 keV were greater than other energies and weighted-average images (P < .05).ConclusionsKiloelectron volt images of 40–50 keV from the second-generation algorithm optimize attenuation on dual-energy CTPA and can potentially aid in interpretation and avoiding nondiagnostic examinations.



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Dual-phase Cone-beam CT-based Navigation Imaging Significantly Enhances Tumor Detectability and Aids Superselective Transarterial Chemoembolization of Liver Cancer

Publication date: Available online 15 February 2018
Source:Academic Radiology
Author(s): Xuesong Yao, Dong Yan, Xianxian Jiang, Xiao Li, Huiying Zeng, Dezhong Liu, Huai Li
Rationale and ObjectivesThe objective of this study was to investigate the impact of a dual-phase cone-beam computed tomography (DP-CBCT)-based navigation imaging during transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) in a perspective randomized study.Materials and MethodsForty-two patients with HCC (39 men, 57 ± 9 years, 13 first-time TACE) underwent TACE using three-dimensional image guidance with automatic detection of tumor-feeding vessels computed from DP-CBCT (early and delayed arterial phases). Forty-nine other patients with HCC (44 men, 55 ± 12 years, 14 first-time TACE) were treated conventionally using digital subtraction angiography (DSA). Tumor detectability in DP-CBCT was compared to DSA and preoperative CT or magnetic resonance (MR) imaging. Tumor-feeding vessel visibility was rated (good, fair, and poor) intraoperatively by the operators. The superselective embolization success rate, the number of DSA acquisitions, fluoroscopy time, and patient radiation dose were collected and compared using paired t test and the Mann-Whitney U test.ResultsTumor detection of DP-CBCT was superior to DSA (100% vs 83%, P = .001) and comparable to CT-MR (96%, P = .456). Tumor and feeder visibilities were significantly enhanced by DP-CBCT (P < .001). Compared to using DSA, more superselective embolization was achieved (60% vs 49%) with less DSA acquisitions (n = 2.6 ± 0.8 vs n = 3.4 ± 0.7, P < .001) and shorter fluoroscopy time (4.1 ± 2.6 vs 7.1 ± 4.2 minutes, P < .001) with a slight increase in patient radiation exposure, that is, air kerma (median: 0.33, first to third quartiles: 0.24–0.48 vs 0.30, 0.24–0.44 Gy; P = .519) and dose-area product (134, 92–181 vs 97, 75–140 Gy⋅cm2, P = .048).ConclusionsDP-CBCT and navigation imaging improve tumor detectability and superselective embolization in TACE.



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Bridging the Gap

Publication date: Available online 15 February 2018
Source:Academic Radiology
Author(s): Sarah Wallace Cater, Sora C. Yoon, Dorothy A. Lowell, James C. Campbell, Gary Sulioti, Rosie Qin, Brian Jiang, Lars J. Grimm
Rationale and ObjectivesWomen make up half of American medical school graduates, but remain underrepresented among radiologists. This study sought to determine whether workforce gender disparities exist in other countries, and to identify any country-specific indices associated with increased female representation.Materials and MethodsIn this cross-sectional study, 95 professional radiology organizations in 75 countries were contacted via email to provide membership statistics, including proportion of female members, female members aged 35 or under, and women in society leadership positions. Country-specific metrics collected included gross domestic product, Gini index, percent female medical school enrollment, and Gender Development Index for the purposes of univariate multiple regression analysis.ResultsTwenty-nine organizations provided data on 184,888 radiologists, representing 26 countries from Europe (n = 12), North America (n = 2), Central/South America (n = 6), Oceania (n = 2), Asia (n = 3), and Africa (n = 1) for a response rate of 34.7% (26/75). Globally, 33.5% of radiologists are female. Women constitute a higher proportion of younger radiologists, with 48.5% of radiologists aged 35 or under being female. Female representation in radiology is lowest in the United States (27.2%), highest in Thailand (85.0%), and most variable in Europe (mean 40.1%, range 28.8%–68.9%). The proportion of female radiologists was positively associated with a country's Gender Development Index (P = .006), percent female medical student enrollment (P = .001), and Gini index (P = .002), and negatively associated with gross domestic product (P = .03).ConclusionsWomen are underrepresented in radiology globally, most notably in the United States. Countries with greater representation of women had higher gender equality and percent female medical school enrollment, suggesting these factors may play a role in the gender gap.



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Utility of rituximab treatment for exophthalmos, myxedema, and osteoarthropathy syndrome resistant to corticosteroids due to Graves’ disease: a case report

Exophthalmos, myxedema, and osteoarthropathy syndrome is a very rare condition that is associated with Graves’ disease. The presence of dermopathy and the involvement of joint/bone tissues indicate that it see...

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Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

Abstract

Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor survival outcome in recurrent and advanced stages. The role of type-specific epigenomics and its clinical significance remain uncertain. We analyzed the methylomic profiles of six benign mucinous adenomas, 24 MuOCs, 103 serous type of epithelial ovarian cancers (SeOCs), and 337 nonepithelial ovarian cancers. MuOC and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of which exhibited low methylation in MuOC and were associated with the response to glucocorticoid, ATP hydrolysis-coupled proton transport, proteolysis involved in the cellular protein catabolic process, and ion transmembrane transport. Hierarchical clustering analysis showed that the profiles of MuOC were similar to colorectal adenocarcinoma, and stomach adenocarcinoma. Genetic interaction network analysis of differentially methylated genes in MuOC showed a dominant network module is the proteasome subunit beta (PSMB) family. Combined functional module and methylation analysis identified PSMB8 as a candidate marker for MuOC. Immunohistochemical staining of PSMB8 used to validate in 94 samples of ovarian tumors (mucinous adenoma, MuOC, or SeOC) and 62 samples of gastrointestinal cancer. PSMB8 was commonly expressed in MuOC and gastrointestinal cancer samples, predominantly as strong cytoplasmic and occasionally weak nuclei staining, but was not expressed in SeOC samples. Carfilzomib, a second-generation proteasome inhibitor, suppressed MuOC cell growth in vitro. This study unveiled a mucinous-type-specific methylation profile and suggests the potential use of a proteasome inhibitor to treat MuOC. This article is protected by copyright. All rights reserved.



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Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery

Abstract

Urine metabolomics have been used to identify biomarkers for clinical diseases. However, inter-individual variations and effect factors need to be further evaluated. In the present study, we explored the urine metabolome in a cohort of 203 health adults, 6 patients with benign bladder lesions, and 53 patients with bladder cancer (BCa) using liquid chromatography coupled with high resolution mass spectrometry. Inter-individual analysis of both healthy controls and bladder cancer patients showed that the urine metabolome was relatively stable. Further analysis indicated that sex and age affect inter-individual variations of urine metabolome. Metabolic pathways such as tryptophan metabolism, the citrate cycle, and pantothenate and CoA biosynthesis were found to be related to sex and age. To eliminate age and sex interference, additional BCa urine metabolomic biomarkers were explored using age and sex-matched urine samples (Test group: 44 health adults vs. 33 patients with BCa). Metabolic profiling of urine could significantly differentiate the cases with cancer from the controls and high-grade from low-grade BCa. A metabolite panel consisting of trans-2-dodecenoylcarnitine, serinyl-valine, feruloyl-2-hydroxyputrescine, and 3-hydroxynonanoyl carnitine were discovered to have good predictive ability for BCa with an area under the curve (AUC) of 0.956 (cross validation: AUC=0.924). A panel of indolylacryloylglycine, N2-galacturonyl-L-lysine, and aspartyl-glutamate was used to establish a robust model for high and low-grade BCa distinction with AUC of 0.937 (cross validation: AUC=0.891).External sample(26 control vs. 20 BCa) validation verified the acceptable accuracy of these models for BCa detection.This study showed that urinary metabolomics is a useful strategy for differential analysis and biomarker discovery. This article is protected by copyright. All rights reserved.



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Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in HER2-positive advanced esophagogastric cancer: A meta-analysis

Abstract

According to the ToGA study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for HER2-positive advanced esophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive esophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in-situ-hybridisation. We compared primary outcome overall survival (OS) of alternative trastuzumab-based regimens to the ToGA regimen. Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated by extraction of the published Kaplan-Meier curves. Incidence counts and toxicity sample-sizes were extracted for adverse events and compared using single-arm proportion meta-analysis in R. Fifteen studies (N=557 patients) were included. OS was significantly longer with regimen trastuzumab plus doublet oxaliplatin and capecitabine/5-FU (median OS=20.7 months) versus ToGA (16.0 months, HR=0.75, 95%CI=0.59-0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S-1 showed no OS difference versus ToGA, but showed a different toxicity profile, including less hand-foot syndrome. Trastuzumab plus cisplatin or capecitabine as singlet backbone showed significantly worse survival and more toxicity versus ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone showed no survival benefit and more toxicity. In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S-1 can substitute capecitabine or 5-FU when specific toxicities are encountered. This article is protected by copyright. All rights reserved.



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NRF2 Addiction in Cancer Cells

Abstract

The KEAP1-NRF2 system is a pivotal defense mechanism against oxidative and electrophilic stress. While transient NRF2 activation in response to stress is beneficial for health, persistent NRF2 activation in cancer cells has deleterious effects on cancer-bearing hosts by conferring therapeutic resistance and aggressive tumorigenic activity on cancer cells. Because NRF2 increases the anti-oxidant and detoxification capability of cancer cells, persistently high levels of NRF2 activity enhance therapeutic resistance of the cancer cells. NRF2 also drives metabolic reprogramming to establish cellular metabolic processes that is advantageous for cell proliferation in cooperation with other oncogenic pathways. Due to these advantages, cancer cells with persistent activation of NRF2 often develop “NRF2 addiction” and exhibit malignant phenotypes leading to poor prognoses in cancer patients. Inhibition of NRF2 is a promising therapeutic approach for NRF2-addicted cancers, and NRF2 inhibitors are being actively developed. However, systemic administration of NRF2 inhibitors might have undesirable effects on cancer-bearing hosts, considering the central roles of NRF2 in cytoprotection. To avoid these side effects, new therapeutic targets besides NRF2 for NRF2-addicted cancers have been actively explored. This review introduces recent studies describing the development and characterization of NRF2-addicted cancers, as well as their potential therapeutic targets. Expected advances in diagnostic and therapeutic interventions for NRF2-addicted cancers are also discussed.

This article is protected by copyright. All rights reserved.



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Self-sampling identifies twice as many women at risk of cervical cancer

Using self-sampling followed by HPV testing, more than twice as many women at risk of developing cervical cancer could be identified and offered preventive treatment. This is shown by researchers at Uppsala University in the first randomised study in the...

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New research highlights how cancer cells repair themselves following proton beam therapy

Collaborative research conducted in Liverpool and Oxford, published in The Red Journal, identifies the specific cellular process that helps cancer cells damaged as a result of proton beam therapy, repair themselves. Proton beam therapy (PBT) is a type of...

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First comparison of common breast cancer tests finds varied accuracy of predictions

Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women. The analysis, published in...

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Genes to predict how women respond to ovarian cancer treatment

Research published in Nature Scientific Reports has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy. The research showed that the genes we inherit can have a significant impact on how the body...

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MicroRNA-365 modulates astrocyte conversion into neuron in adult rat brain after stroke by targeting Pax6

Abstract

Reactive astrocytes induced by ischemia can transdifferentiate into mature neurons. This neurogenic potential of astrocytes may have therapeutic value for brain injury. Epigenetic modifications are widely known to involve in developmental and adult neurogenesis. PAX6, a neurogenic fate determinant, contributes to the astrocyte-to-neuron conversion. However, it is unclear whether microRNAs (miRs) modulate PAX6-mediated astrocyte-to-neuron conversion. In the present study we used bioinformatic approaches to predict miRs potentially targeting Pax6, and transient middle cerebral artery occlusion (MCAO) to model cerebral ischemic injury in adult rats. These rats were given striatal injection of glial fibrillary acidic protein targeted enhanced green fluorescence protein lentiviral vectors (Lv-GFAP-EGFP) to permit cell fate mapping for tracing astrocytes-derived neurons. We verified that miR-365 directly targets to the 3′-UTR of Pax6 by luciferase assay. We found that miR-365 expression was significantly increased in the ischemic brain. Intraventricular injection of miR-365 antagomir effectively increased astrocytic PAX6 expression and the number of new mature neurons derived from astrocytes in the ischemic striatum, and reduced neurological deficits as well as cerebral infarct volume. Conversely, miR-365 agomir reduced PAX6 expression and neurogenesis, and worsened brain injury. Moreover, exogenous overexpression of PAX6 enhanced the astrocyte-to-neuron conversion and abolished the effects of miR-365. Our results demonstrate that increase of miR-365 in the ischemic brain inhibits astrocyte-to-neuron conversion by targeting Pax6, whereas knockdown of miR-365 enhances PAX6-mediated neurogenesis from astrocytes and attenuates neuronal injury in the brain after ischemic stroke. Our findings provide a foundation for developing novel therapeutic strategies for brain injury.

Thumbnail image of graphical abstract

Main Points

  • Ischemic stroke upregulates miR-365 in rat brain.
  • MiR-365 inhibits stroke-induced astrocyte-to-neuron conversion by targeting Pax6.
  • MiR-365 knockdown promotes PAX6-mediated astrocyte-to-neuron conversion and brain repair after stroke.


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IJERPH, Vol. 15, Pages 353: Is the Definition of Roma an Important Matter? The Parallel Application of Self and External Classification of Ethnicity in a Population-Based Health Interview Survey

IJERPH, Vol. 15, Pages 353: Is the Definition of Roma an Important Matter? The Parallel Application of Self and External Classification of Ethnicity in a Population-Based Health Interview Survey

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020353

Authors: Eszter Anna Janka Ferenc Vincze Róza Ádány János Sándor

The Roma population is typified by a poor and, due to difficulties in ethnicity assessment, poorly documented health status. We aimed to compare the usefulness of self-reporting and observer-reporting in Roma classification for surveys investigating differences between Roma and non-Roma populations. Both self-reporting and observer-reporting of Roma ethnicity were applied in a population-based health interview survey. A questionnaire was completed by 1849 people aged 18–64 years; this questionnaire provided information on 52 indicators (morbidity, functionality, lifestyle, social capital, accidents, healthcare use) indicators. Multivariate logistic regression models controlling for age, sex, education and employment were used to produce indicators for differences between the self-reported Roma (N = 124) and non-Roma (N = 1725) populations, as well as between observer-reported Roma (N = 179) and non-Roma populations (N = 1670). Differences between interviewer-reported and self-reported individuals of Roma ethnicity in statistical inferences were observed for only seven indicators. The self-reporting approach was more sensitive for two indicators, and the observer-reported assessment for five indicators. Based on our results, the self-reported identity can be considered as a useful approach, and the application of observer-reporting cannot considerably increase the usefulness of a survey, because the differences between Roma and non-Roma individuals are much bigger than the differences between indicators produced by self-reported or observer-reported data on individuals of Roma ethnicity.



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Pediatric astrocytic tumor grading: comparison between arterial spin labeling and dynamic susceptibility contrast MRI perfusion

Abstract

Purpose

The aim of this study was to compare arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) MRI perfusion with respect to diagnostic performance in tumor grading in pediatric patients with low- and high-grade astrocytic tumors (AT).

Methods

We retrospectively analyzed 37 children with histologically proven treatment naive low- and high-grade AT who underwent concomitant pre-operative ASL and DSC MRI perfusion. Studies were performed on a 1.5 T scanner, and a pulsed technique was used for ASL. DSC data were post-processed with a leakage correction software. Normalization of tumor perfusion parameters was performed with contralateral normal appearing gray matter. Normalized cerebral blood volume (nCBV) values in the most perfused area of each neoplasm were compared with normalized DSC-derived cerebral blood flow (nDSC-CBF) and ASL-derived cerebral blood flow (nASL-CBF) data, and correlated with WHO tumor grade. Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation, and receiver operating characteristic (ROC) analysis.

Results

A significant correlation was demonstrated between DSC and ASL data (p < 0.001). Significant differences in terms of DSC and ASL data were found between low- and high-grade AT (p < 0.001). ROC analysis demonstrated similar performances between all parameters in predicting tumor grade (nCBV: AUC 0.96, p < 0.001; nDSC-CBF: AUC 0.98, p < 0.001; nASL-CBF: AUC 0.96, p < 0.001).

Conclusions

Normalized pulsed ASL performed with a 1.5 T scanner provides comparable results to DSC MRI perfusion in pediatric AT and may allow distinction between high- and low-grade AT.



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Joan Murdoch

bmj;360/feb16_6/k700/FAF1faBorn in Silsden, Joan Murdoch went to Leeds University medical school during the war, following in the footsteps of her older brother. She was very proud to have qualified...
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Peter Giles

bmj;360/feb16_8/k709/FAF1faAfter various house jobs, Peter Giles spent three years in the navy (in lieu of national service) and, after two years in general practice in west Yorkshire and Lancashire,...
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Param Jeet Singh Sandhu

bmj;360/feb16_5/k708/FAF1faParam Jeet Singh Sandhu (known to his friends as ͞PJ) had a reputation for being a compassionate and caring GP with a dedicated following of devoted patients and staff. PJ...
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Isabel McCarlie

bmj;360/feb16_4/k702/FAF1faIsabel McCarlie grew up in Stranraer in south-west Scotland. During her childhood she developed a love for sailing and outdoor swimming that continued throughout her life....
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Margaret Anne Whittingham

bmj;360/feb16_3/k699/FAF1faMargaret Anne (“Anne”) was the daughter of Frederick J Nattrass, professor of medicine at King’s College. She married Peter D G V Whittingham two days after they both...
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