3D Registration of mpMRI for Assessment of Prostate Cancer Focal Therapy

Publication date: Available online 6 November 2017
Source:Academic Radiology
Author(s): Clément Orczyk, Andrew B. Rosenkrantz, Artem Mikheev, Arnauld Villers, Myriam Bernaudin, Samir S. Taneja, Samuel Valable, Henry Rusinek
Rationale and ObjectivesThis study aimed to assess a novel method of three-dimensional (3D) co-registration of prostate magnetic resonance imaging (MRI) examinations performed before and after prostate cancer focal therapy.Materials and MethodsWe developed a software platform for automatic 3D deformable co-registration of prostate MRI at different time points and applied this method to 10 patients who underwent focal ablative therapy. MRI examinations were performed preoperatively, as well as 1 week and 6 months post treatment. Rigid registration served as reference for assessing co-registration accuracy and precision.ResultsSegmentation of preoperative and postoperative prostate revealed a significant postoperative volume decrease of the gland that averaged 6.49 cc (P = .017). Applying deformable transformation based on mutual information from 120 pairs of MRI slices, we refined by 2.9 mm (max. 6.25 mm) the alignment of the ablation zone, segmented from contrast-enhanced images on the 1-week postoperative examination, to the 6-month postoperative T2-weighted images. This represented a 500% improvement over the rigid approach (P = .001), corrected by volume. The dissimilarity by Dice index of the mapped ablation zone using deformable transformation vs rigid control was significantly (P = .04) higher at the ablation site than in the whole gland.ConclusionsOur findings illustrate our method's ability to correct for deformation at the ablation site. The preliminary analysis suggests that deformable transformation computed from mutual information of preoperative and follow-up MRI is accurate in co-registration of MRI examinations performed before and after focal therapy. The ability to localize the previously ablated tissue in 3D space may improve targeting for image-guided follow-up biopsy within focal therapy protocols.



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Imaging Facilities' Adherence to PI-RADS v2 Minimum Technical Standards for the Performance of Prostate MRI

Publication date: Available online 6 November 2017
Source:Academic Radiology
Author(s): Steven J. Esses, Samir S. Taneja, Andrew B. Rosenkrantz
PurposeThis study aimed to assess variability in imaging facilities' adherence to the minimum technical standards for prostate magnetic resonance imaging acquisition established by Prostate Imaging-Reporting and Data System (PI-RADS) version 2 (v2).MethodsA total of 107 prostate magnetic resonance imaging examinations performed at 107 unique imaging facilities after the release of PI-RADS v2 and that were referred to a tertiary care center for secondary interpretation were included. Image sets, DICOM headers, and outside reports were reviewed to assess adherence to 21 selected PI-RADS v2 minimum technical standards.ResultsHardware arrangements were 23.1%, 1.5T without endorectal coil; 7.7%, 1.5T with endorectal coil; 63.5%, 3T without endorectal coil; and 5.8%, 3T with endorectal coil. Adherence to minimum standards was lowest on T2 weighted imaging (T2WI) for frequency resolution ≤0.4 mm (16.8%) and phase resolution ≤0.7 mm (48.6%), lowest on diffusion-weighted imaging (DWI) for field of view (FOV) 120–220 mm (30.0%), and lowest on dynamic contrast-enhanced (DCE) imaging for slice thickness 3 mm (33.3%) and temporal resolution <10 s (31.5%). High b-value (≥1400 s/mm²) images were included in 58.0% (calculated in 25.9%). Adherence to T2WI phase resolution and DWI inter-slice gap were greater (P < .05) at 3T than at 1.5T. Adherence did not differ (P > .05) for any parameter between examinations performed with and without an endorectal coil. Adherence was greater for examinations performed at teaching facilities for T2WI slice thickness and DCE temporal resolution (P < .05). Adherence was not better for examinations performed in 2016 than in 2015 for any parameter (P > .05).ConclusionFacilities' adherence to PI-RADS v2 minimum technical standards was variable, being particularly poor for T2WI frequency resolution and DCE temporal resolution. The standards warrant greater community education. Certain technical standards may be too stringent, and revisions should be considered.



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Automated Radiology-Operative Note Communication Tool; Closing the Loop in Musculoskeletal Imaging

Publication date: Available online 6 November 2017
Source:Academic Radiology
Author(s): William Moore, Ankur Doshi, Priya Bhattacharji, Soterios Gyftopoulos, Gina Ciavarra, Danny Kim, Michael Recht
Rationale and ObjectivesCorrelation of imaging studies and reference standard outcomes is a significant challenge in radiology. This study evaluates the effectiveness of a new communication tool by assessing the ability of this system to correctly match the imaging studies to arthroscopy reports and qualitatively assessing radiologist behavior before and after the implementation of this system.Materials and MethodsUsing a commercially available communication or educational tool and applying a novel matching rule algorithm, radiology and arthroscopy reports were matched from January 17, 2017 to March 1, 2017 based on anatomy. The interpreting radiologist was presented with email notifications containing the impression of the imaging report and the entire arthroscopy report. Total correlation rate of appropriate report pairings, modality-specific correlation rate, and the anatomy-specific correlation rate were calculated. Radiologists using the system were given a survey.ResultsOverall correlation rate for all musculoskeletal imaging was 83.1% (433 or 508). Low correlation was found in fluoroscopic procedures at 74.4%, and the highest correlation was found with ultrasound at 88.4%. Anatomic location varied from 51.6% for spine to 98.8% for hips and pelvis studies.Survey results revealed 87.5% of the respondents reporting being either satisfied or very satisfied with the new communication tool. The survey also revealed that some radiologists reviewed more cases than before.ConclusionsMatching of radiology and arthroscopy reports by anatomy allows for excellent report correlation (83.1%). Automated correlation improves the quality and efficiency of feedback to radiologists, providing important opportunities for learning and improved accuracy.



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Can Radiologists Learn From Airport Baggage Screening?

Publication date: Available online 6 November 2017
Source:Academic Radiology
Author(s): Andrew Phelps, Andrew L. Callen, Peter Marcovici, David M. Naeger, John Mongan, Emily M. Webb
Rationale and ObjectivesFor both airport baggage screeners and radiologists, low target prevalence is associated with low detection rate, a phenomenon known as "prevalence effect." In airport baggage screening, the target prevalence is artificially increased with fictional weapons that are digitally superimposed on real baggage. This strategy improves the detection rate of real weapons and also allows airport supervisors to monitor screener performance. A similar strategy using fictional patients could be applied in radiology. The purpose of this study was twofold: (1) to review the psychophysics literature regarding low target prevalence and (2) to survey radiologists' attitudes toward using fictional patients as a quality assurance tool.Materials and MethodsWe reviewed the psychophysics literature on low target prevalence and airport x-ray baggage screeners. An online survey was e-mailed to all members of the Association of University Radiologists to determine their attitudes toward using fictional patients in radiology.ResultsOf the 1503 Association of University Radiologists member recipients, there were 153 respondents (10% response rate). When asked whether the use of fictional patients was a good idea, the responses were as follows: disagree (44%), neutral (25%), and agree (31%). The most frequent concern was the time taken away from doing clinical work (89% of the respondents).ConclusionsThe psychophysics literature supports the use of fictional targets to mitigate the prevalence effect. However, the use of fictional patients is not a popular idea among academic radiologists.



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Accuracy of Computed Tomographic Enterography for Obscure Gastrointestinal Bleeding

Publication date: Available online 6 November 2017
Source:Academic Radiology
Author(s): Bosheng He, Jushun Yang, Jing Xiao, Jinhua Gu, Feixiang Chen, Lin Wang, Junbo Qian, Shenchu Gong
Rationale and ObjectivesObscure gastrointestinal bleeding (OGIB) is the bleeding from the gastrointestinal tract without definite source that persists and recurs after a negative endoscopic evaluation. The study aimed to systematically evaluate the diagnostic accuracy of computed tomography enterography on OGIB detection by meta-analysis.Materials and MethodsStudies were searched in relevant databases. With predefined inclusion criteria, eligible studies were included, followed by quality assessment using the Quality Assessment of Diagnostic Accuracy Studies scoring system. The Meta-DiSc software was used to implement the meta-analysis, and sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with their 95% confidence intervals (CIs) were used as the effect size. Publication bias was determined by Egger test.ResultsA set of nine studies was included in this meta-analysis, having a relatively high quality. Under the random effects model, the pooled sensitivity and specificity were 0.724 (95% CI: 0.651–0.789) and 0.752 (95% CI: 0.691–0.807), respectively. Under the fixed effects model, the pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 2.949 (95% CI: 2.259–3.850), 0.393 (95% CI: 0.310–0.497), and 9.452 (95% CI: 5.693–15.692), respectively. The area under curve of the summary receiver operating characteristic curve was 0.7916 (95% CI: 0.723–0.860). No obvious publication bias was detected (t = 1.62, P = .181).ConclusionsComputed tomography enterography might be used as a complementary to video capsule endoscopy instead of an alternative for the detection of OGIB.



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Medication related osteonecrosis of the jaws associated with targeted therapy as monotherapy and in combination with anti-resorptives. a report of seven cases from the copenhagen ONJ cohort

To report cases of medication related osteonecrosis of the jaws (MRONJ) associated with Targeted Therapy (TT) with and without concomitant anti-resorptive treatment, among The Copenhagen ONJ Cohort, which includes all consecutive cases of MRONJ seen in Copenhagen.

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Effects of single condylar neck fracture without condylar cartilage injury on traumatic heterotopic ossification around temporomandibular joint in mice

In this study, we try to explore the effects of single condylar neck fracture without condylar cartilage injury during the pathogenesis process of traumatic heterotopic ossification around temporomandibular joint (THO-TMJ).

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Clinical pathologic conference: diffuse papillomatous lesions of the gingiva with posterolateral neck skin tags

A 47-year-old Caucasian female initially presented to the General Dentistry Clinic at Vanderbilt University Medical Center with a chief complaint of loose anterior teeth and a need for a dental check-up. The patient was noted to have several carious teeth and moderate, generalized periodontal disease. In addition, she presented with numerous 1-2 mm papillomatous lesions involving attached gingiva and unattached alveolar mucosa. The patient was referred to the Oral & Maxillofacial Surgery Department at Vanderbilt for further evaluation and consultation regarding her intraoral lesions.

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Pre-Operative Pulmonary Lesion Marking in Preparation for Fluoroscopic Wedge Resection – Rates of Success, Complications and Pathology Outcomes

Publication date: Available online 6 November 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Babatunde Olaiya, Charles A. Gilliland, Seth D. Force, Felix G. Fernandez, Manu S Sancheti, William C. Small
PurposeIn this study, we describe our experience of lesion marking with fiducial markers (FM) and microcoils (MC) facilitating same-day surgical wedge resection, including success rates, pathology outcomes, and complications. We also explored patient/nodular characteristics associated with developing complications.Materials and MethodsAn IRB-approved single institutional retrospective study of 136 patients who had 148 pulmonary nodules was conducted. All patients had CT-guided pulmonary nodule labeling with either FM (121) or MC (15) patients with plan for same-day fluoroscopic-guided wedge-resection.Results133 of 136 (98%) of patients had successful same-day wedge-resection as planned; two had delayed but successful wedge-resection surgery due to complications at the time of marker placement (fiducial embolization and hemorrhage/pneumothorax, respectively). A third patient ultimately needed lobectomy due to deep lesion location. Eighty percent [118/148] of resected nodules were malignant. 68% of the total group of patients [93/136] had mild complications of various types including hemorrhage [44/136, 32%], pneumothorax [35/136, 26%], a combination of both hemorrhage and pneumothorax [10/136, 7%] or migration/embolization [4/136, 3%]. Depth of nodule from skin (p=0.011) and pleura (p=0.027) was significantly associated with complications.ConclusionCT-guided marking of small and/or deep pulmonary lesions using either fiducial markers or microcoils provides an effective means to aid surgeons to accomplish minimally invasive wedge-resection. The importance of the success of this technique is supported by the high incidence (80%) of malignant lesion etiology found at post-resection pathology. Although complications occurred, the vast majority were mild and did not alter planned same-day resection.



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With or without consolidation chemotherapy using cisplatin/5-FU after concurrent chemoradiotherapy in stage II–III squamous cell carcinoma of the esophagus: A propensity score-matched analysis

The benefit of consolidation chemotherapy for locally advanced squamous cell carcinoma of the esophagus is unknown. The aim of this study was to investigate the efficacy of consolidation chemotherapy with cisplatin and 5-fluorouracil (5-FU) after concurrent chemoradiotherapy (CCRT) with the same agents in patients with stage II–III disease.

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Association between treatment planning and delivery factors and disease progression in prostate cancer radiotherapy: Results from the TROG 03.04 RADAR trial

To evaluate the impact of treatment planning and delivery factors on treatment outcome as measured by post-treatment disease progression.

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Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy

RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive.

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Post-radiochemotherapy PET radiomics in head and neck cancer – The influence of radiomics implementation on the reproducibility of local control tumor models

This study investigated an association of post-radiochemotherapy (RCT) PET radiomics with local tumor control in head and neck squamous cell carcinoma (HNSCC) and evaluated the models against two radiomics software implementations.

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Ventilation measured on clinical 4D-CBCT: Increased ventilation accuracy through improved image quality

Ventilation measured on 4D cone-beam computed tomography (CBCT) using deformable image registration (DIR) may predict specific radiation sensitivity, but the measurement is affected by the current image quality. With 4D computed tomography (CT) measured ventilation acting as a gold standard the current study investigates if image improvements increase the accuracy of 4D-CBCT measured ventilation.

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Clustering of multi-parametric functional imaging to identify high-risk subvolumes in non-small cell lung cancer

We aimed to identify tumour subregions with characteristic phenotypes based on pre-treatment multi-parametric functional imaging and correlate these subregions to treatment outcome. The subregions were created using imaging of metabolic activity (FDG-PET/CT), hypoxia (HX4-PET/CT) and tumour vasculature (DCE-CT).

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Improved diagnostic performance of transluminal attenuation gradient in combination with morphological evaluation of coronary artery stenosis using 320-row computed tomography

Abstract

Purpose

To assess the utility of transluminal attenuation gradient (TAG) in combination with coronary computed tomography angiography (CTA) for detecting obstructive coronary artery stenosis.

Materials and methods

We retrospectively evaluated coronary CTA data in 35 consecutive patients who underwent invasive coronary angiography (ICA). We compared the diagnostic performance of TAG with that of quantitative coronary angiography, which we used as the reference standard. For the combination of TAG and coronary CTA, we designed a logical conjunction model (CCTA&&TAG) as well as a logical disjunction model (CCTA||TAG), and evaluated their diagnostic accuracies.

Results

Among 130 vessels of 35 patients, 30 lesions (23%) showed significant stenosis on ICA. TAG predicted significant coronary artery stenosis with a sensitivity of 75%, specificity of 63%, positive predictive value of 40%, negative predictive value of 89%, and accuracy of 66%, and had a cutoff value of − 15.4 HU/10 mm. The respective values for CCTA&&TAG were 73, 98, 88, 90, and 90%; those for CCTA||TAG were 94, 61, 56, 94, and 72%. CCTA&&TAG improved the diagnostic accuracy significantly more than CCTA||TAG.

Conclusion

TAG in conjunction with coronary CTA improves the diagnostic accuracy of coronary CTA.

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Hip shape is symmetric, non-dependent on limb dominance and gender-specific: implications for femoroacetabular impingement. A 3D CT analysis in asymptomatic subjects

Abstract

Objective

To determine the reference intervals (RefInt) of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in asymptomatic hips with computed tomography (CT) and determine their dependence on age, side, limb dominance and sex.

Methods

We prospectively included 590 patients and evaluated 1111 hips with semi-automated CT analysis. We calculated overall, side- and sex-specific parameters for imaging signs of cam [omega and alpha angle (α°)] and pincer-type morphology [acetabular version (ACvers), lateral centre-edge angle (LCEA) and cranio-caudal coverage].

Results

Hip shape was symmetrical and did not depend on limb dominance. The 95% RefInt limits were sex-different for all cam-type parameters and extended beyond current abnormal thresholds. Specifically, the upper limits of RefInt for α° at 12:00, 1:30 and 3:00 o'clock positions were 56°, 70° and 58°, respectively, and 45° for LCEA. Acetabular morphology varied between age groups, with a trend toward an LCEA/ACvers increase over time.

Conclusion

Our morphometric measurements can be used to estimate normal hip morphology in asymptomatic individuals. Notably they extended beyond current thresholds used for FAI imaging diagnosis, which was most pronounced for cam-type parameters. We suggest the need to reassess α° RefInt and consider a 60° threshold for the 12:00/3:00 positions and 65-70° for other antero-superior positions.

Key Points

• Hip shape is symmetrical regardless of limb dominance.

• Pincer/cam morphology is frequent in asymptomatic subjects (20 and 71%, respectively).

• LCEA and acetabular version increases with age (5-7° between opposite age groups).

• Femoral morphology is stable after physeal closure (in the absence of pathology).

• Alpha and omega angle thresholds should be set according to sex.

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Prognostic value of 18F–choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide

Abstract

Purpose

The role of 18F–choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide.

Methods

We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42–90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS.

Results

We observed a median SMTV of 130 cm³, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034).

Conclusions

Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

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Gender and age make no difference in the re-irradiation of painful bone metastases: A secondary analysis of the NCIC CTG SC.20 randomized trial

Publication date: Available online 5 November 2017
Source:Radiotherapy and Oncology
Author(s): Ronald Chow, Keyue Ding, Vithusha Ganesh, Ralph M. Meyer, Yvette M. van der Linden, Daniel Roos, William F. Hartsell, Peter Hoskin, Jackson S.Y. Wu, Abdenour Nabid, Manouk van Acht, Rinus Wanders, Scott Babington, William F. Demas, Carolyn F. Wilson, Rebecca K.S. Wong, Michael Brundage, Liting Zhu, Edward Chow
Background and purposePatient's gender and age may influence physicians in prescribing palliative radiotherapy. The purpose of this secondary analysis of the National Cancer Institute of Canada Clinical Trials Group Symptom Control Trial SC.20 was to explore the gender and age differences in pain and patient reported outcomes in cancer patients with bone metastases undergoing re-irradiation.Materials and methodsResponse to radiation was evaluated using the International Bone Metastases Consensus Endpoint Definitions. Patients completed the Brief Pain Inventory (BPI) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (C30) before and 2 months after re-irradiation.ResultsA total of 847 patients were analyzed. At baseline, men had more dyspnea, and mild pain. Older patients consumed less analgesic. More women reported clinically significant improvement in mood and enjoyment of life in the BPI after radiation. Similarly, younger patients reported better improvement in enjoyment of life. There were no significant gender or age differences in overall survival, response to radiation, or in C30 scores at 2 months.ConclusionSimilar benefit in terms of pain relief was observed across all patient groups. Cancer patients with bone metastases should be offered palliative re-irradiation irrespective of gender or age.Trial Registration: NCT00080912; http://ift.tt/2hL93EO.



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Radiation toxicity in patients with collagen vascular disease and intrathoracic malignancy treated with modern radiation techniques

Publication date: Available online 5 November 2017
Source:Radiotherapy and Oncology
Author(s): Kevin Diao, Yu-Hui Chen, Paul J. Catalano, Stephanie Lee, Nastaran Milani, Joseph H. Killoran, Elizabeth H. Baldini, Aileen B. Chen, David E. Kozono, Raymond H. Mak
Background and purposeThere is concern that patients with collagen vascular disease (CVD) are at higher risk of developing radiation toxicity. We analyzed radiation toxicities in patients with intrathoracic malignancy and CVD treated using modern radiotherapy.Materials and methodsThis single-institution retrospective study included 31 patients with CVD and 825 patients without CVD treated from 1998 to 2014. Radiation esophagitis (RE) and radiation pneumonitis (RP) were scored by RTOG scales. RE was analyzed with logistic regression and RP with Cox regression.ResultsCVD patients experienced similar grade ≥3 RE compared to control patients (23% vs. 19%, p = 0.64) but more grade ≥3 RP (26% vs. 10%, p = 0.01). There was no significant association between CVD subtype and toxicities. In multivariate analysis, CVD and lung V20 >30% were associated with grade ≥3 RP. We identified V20 ≤30%, V5 ≤50%, and MLD ≤18 Gy as dose thresholds in patients with CVD. CVD patients with mild severity disease and only 1 organ system involved were at low risk for RP.ConclusionsPatients with CVD may be at higher risk of RP. However, CVD patients may be offered curative thoracic RT with particular attention to risk-reduction strategies and maintaining recommended dose constraints as described in this study.



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Radioactive iodine capture and storage from water using magnetite nanoparticles encapsulated in polypyrrole.

Radioactive iodine capture and storage from water using magnetite nanoparticles encapsulated in polypyrrole.

J Hazard Mater. 2017 Nov 02;344:576-584

Authors: Harijan DKL, Chandra V, Yoon T, Kim KS

Abstract
The effective capture and storage of radioactive iodine is of importance for nuclear waste storage during nuclear power station accidents. Here we report Fe3O4@PPy powder containing ∼12nm magnetite (Fe3O4) nanoparticles encapsulated in the polypyrrole (PPy) matrix. It shows 1627mg/g uptake of iodine dissolved in water, within 2h at room temperature. Fe3O4@PPy is ferromagnetic in nature and can be separated from water using external magnetic field. The nitrogen gas sweeping test at 30°C shows release of 2% iodine from iodine adsorbed Fe3O4@PPy, revealing stable storage of iodine for a moderate period. The iodine-adsorbed magnetic powder can be regenerated by washing with ethanol. The XPS spectrum of iodine adsorbed Fe3O4@PPy confirmed the presence of polyiodides (I3(-) and I5(-)) bound to the PPy surface. This excellent iodine capture and storage from iodine contaminated water is an environment friendly, inexpensive and large scale method.

PMID: 29102640 [PubMed - as supplied by publisher]

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Patient satisfaction with Radioguided Occult Lesion Localisation using iodine-125 seeds ('ROLLIS') versus conventional hookwire localisation.

Patient satisfaction with Radioguided Occult Lesion Localisation using iodine-125 seeds ('ROLLIS') versus conventional hookwire localisation.

Eur J Surg Oncol. 2017 Oct 16;:

Authors: Ong JSL, Teh J, Saunders C, Bourke AG, Lizama C, Newton J, Phillips M, Taylor DB

Abstract
BACKGROUND: Women with impalpable or poorly palpable breast cancer require radiologically guided localisation prior to breast conserving surgery. Radioguided Occult Lesion Localisation using Iodine-125 Seed (ROLLIS) is an emerging alternative to conventional Hookwire Localisation (HWL). We compared ROLLIS with conventional HWL with respect to patient reported stress and discomfort related to the localisation procedure.
PATIENTS AND METHODS: From September 2013 to January 2016, women who were eligible for breast conserving surgery with impalpable or poorly palpable histologically confirmed invasive or in-situ carcinoma were recruited to the multi-centre ROLLIS randomised controlled trial and underwent either ROLLIS or HWL. Following surgery, a questionnaire was administered to each participant regarding the stress and discomfort related to the localisation procedure. Multivariate analysis was performed to compare the primary outcome of patient-reported stress and discomfort between localisation groups.
RESULTS: 218 participants with 220 lesions were randomised and underwent breast conserving surgery following localisation. 201 (92.2%) and 202 (92.7%) of participants provided responses to the stress and discomfort components of the questionnaire respectively. HWL was associated with a statistically significant increased odds of greater stress and discomfort when compared to ROLLIS (OR = 2.07, p = 0.01 and OR = 1.94, p = 0.01 respectively). Insertion of multiple localisation devices was also associated with increased stress (OR = 5.68, p < 0.01) and discomfort (OR = 2.96, p < 0.01).
CONCLUSION: When compared with conventional HWL, ROLLIS is associated with significantly less stress and discomfort for patients prior to breast conserving surgery.

PMID: 29102440 [PubMed - as supplied by publisher]

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ACR Appropriateness Criteria(®) Penetrating Neck Injury.

ACR Appropriateness Criteria(®) Penetrating Neck Injury.

J Am Coll Radiol. 2017 Nov;14(11S):S500-S505

Authors: Expert Panels on Neurologic and Vascular Imaging:, Schroeder JW, Ptak T, Corey AS, Ahmed O, Biffl WL, Brennan JA, Chandra A, Ginsburg M, Hanley M, Hunt CH, Johnson MM, Kennedy TA, Patel ND, Policeni B, Reitman C, Steigner ML, Stiver SI, Strax R, Whitehead MT, Dill KE

Abstract
In patients with penetrating neck injuries with clinical soft injury signs, and patients with hard signs of injury who do not require immediate surgery, CT angiography of the neck is the preferred imaging procedure to evaluate extent of injury. Other modalities, such as radiography and fluoroscopy, catheter-based angiography, ultrasound, and MR angiography have their place in the evaluation of the patient, depending on the specific clinical situation and question at hand. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

PMID: 29101988 [PubMed - in process]

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ACR Appropriateness Criteria(®) Cranial Neuropathy.

ACR Appropriateness Criteria(®) Cranial Neuropathy.

J Am Coll Radiol. 2017 Nov;14(11S):S406-S420

Authors: Expert Panel on Neurologic Imaging:, Policeni B, Corey AS, Burns J, Conley DB, Crowley RW, Harvey HB, Hoang J, Hunt CH, Jagadeesan BD, Juliano AF, Kennedy TA, Moonis G, Pannell JS, Patel ND, Perlmutter JS, Rosenow JM, Schroeder JW, Whitehead MT, Cornelius RS

Abstract
Evaluation of cranial neuropathy can be complex given the different pathway of each cranial nerve as well as the associated anatomic landmarks. Radiological evaluation requires imaging of the entire course of the nerve from its nucleus to the end organ. MRI is the modality of choice with CT playing a complementary role, particularly in the evaluation of the bone anatomy. Since neoplastic and inflammatory lesions are prevalent on the differential diagnosis, contrast enhanced studies are preferred when possible. The American College of Radiology Appropriateness Criteria are evidencebased guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

PMID: 29101981 [PubMed - in process]

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IJMS, Vol. 18, Pages 2343: Two Paralogous Genes Encoding Auxin Efflux Carrier Differentially Expressed in Bitter Gourd (Momordica charantia)

IJMS, Vol. 18, Pages 2343: Two Paralogous Genes Encoding Auxin Efflux Carrier Differentially Expressed in Bitter Gourd (Momordica charantia)

International Journal of Molecular Sciences doi: 10.3390/ijms18112343

Authors: Yi-Li Li Yun-Shan Lin Pung-Ling Huang Yi-Yin Do

The phytohormone auxin regulates various developmental programs in plants, including cell growth, cell division and cell differentiation. The auxin efflux carriers are essential for the auxin transport. To show an involvement of auxin transporters in the coordination of fruit development in bitter gourd, a juicy fruit, we isolated novel cDNAs (referred as McPIN) encoding putative auxin efflux carriers, including McPIN1, McPIN2 (allele of McPIN1) and McPIN3, from developing fruits of bitter gourd. Both McPIN1 and McPIN3 genes possess six exons and five introns. Hydropathy analysis revealed that both polypeptides have two hydrophobic regions with five transmembrane segments and a predominantly hydrophilic core. Phylogenetic analyses revealed that McPIN1 shared the highest homology to the group of Arabidopsis, cucumber and tomato PIN1, while McPIN3 belonged to another group, including Arabidopsis and tomato PIN3 as well as PIN4. This suggests different roles for McPIN1 and McPIN3 in auxin transport involved in the fruit development of bitter gourd. Maximum mRNA levels for both genes were detected in staminate and pistillate flowers. McPIN1 is expressed in a particular period of early fruit development but McPIN3 continues to be expressed until the last stage of fruit ripening. Moreover, these two genes are auxin-inducible and qualified as early auxin-response genes. Their expression patterns suggest that these two auxin transporter genes play a pivotal role in fruit setting and development.

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Rapid onset of osteonecrosis of the jaw in patients switching from bisphosphonates to denosumab.

Rapid onset of osteonecrosis of the jaw in patients switching from bisphosphonates to denosumab.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Sep 28;:

Authors: Yarom N, Lazarovici TS, Whitefield S, Weissman T, Wasserzug O, Yahalom R

Abstract
OBJECTIVE: The aim of this study was to determine whether osteonecrosis of the jaw (ONJ) developed more rapidly in patients who switched from bisphosphonates (BP) treatment to denosumab than in patients who received only denosumab.
STUDY DESIGN: This was a retrospective cohort study conducted at a tertiary referral center. Thirty-one patients with ONJ met the inclusion criteria.
RESULTS: Twenty-two patients who had been on BP were switched to denosumab (BP + D), whereas 9 patients received only denosumab. Both groups were similar for the known ONJ risk factors, that is, age, diabetes mellitus, and smoking. The number and cumulative doses of denosumab before the onset of ONJ symptoms were significantly lower among the BP + D group compared with the denosumab-only group (P = .025 and .018, respectively). In the BP + D group, ONJ symptoms developed in 9 patients (41%) following the administration of ≤3 denosumab doses compared with ONJ developing in only 1 patient (11%) who was naïve to BP. ONJ developed spontaneously without any known triggering event in 72.7% of patients in the BP + D group and in 77.8% of patients in the denosumab-only group.
CONCLUSIONS: Denosumab-induced ONJ might develop rapidly in patients previously treated with BP. ONJ developed spontaneously in most patients treated with denosumab. In light of our sample being small, there is need for further investigation on our conclusions.

PMID: 29102242 [PubMed - as supplied by publisher]

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Examensklausur: Tattoo nach Anleitung

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Die Vertragsübernahme als Regelungsgegenstand des UN-Kaufrecht

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The Withdrawal of Hungary’s Declarations under the CISG – Law and Policy

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Die Vertragsstaateneigenschaft Hongkongs und Macaus unter dem UN-Kaufrecht

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RT @Cheryl_Cruwys : 'We should be taking breast density much more seriously' #breastcancer https://t.co/OCHNlHFMq5

RT @Cheryl_Cruwys : 'We should be taking breast density much more seriously' #breastcancer https://t.co/OCHNlHFMq5

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Differential Microbial Diversity in Drosophila melanogaster: Are Fruit Flies Potential Vectors of Opportunistic Pathogens?

Drosophila melanogaster has become a model system to study interactions between innate immunity and microbial pathogens, yet many aspects regarding its microbial community and interactions with pathogens remain unclear. In this study wild D. melanogaster were collected from tropical fruits in Puerto Rico to test how the microbiota is distributed and to compare the culturable diversity of fungi and bacteria. Additionally, we investigated whether flies are potential vectors of human and plant pathogens. Eighteen species of fungi and twelve species of bacteria were isolated from wild flies. The most abundant microorganisms identified were the yeast Candida inconspicua and the bacterium Klebsiella sp. The yeast Issatchenkia hanoiensis was significantly more common internally than externally in flies. Species richness was higher in fungi than in bacteria, but diversity was lower in fungi than in bacteria. The microbial composition of flies was similar internally and externally. We identified a variety of opportunistic human and plant pathogens in flies such as Alcaligenes faecalis, Aspergillus flavus, A. fumigatus, A. niger, Fusarium equiseti/oxysporum, Geotrichum candidum, Klebsiella oxytoca, Microbacterium oxydans, and Stenotrophomonas maltophilia. Despite its utility as a model system, D. melanogaster can be a vector of microorganisms that represent a potential risk to plant and public health.

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The Influence of 3D Printing on Global Container Multimodal Transport System

Container multimodal transport system was an important promoter of postwar globalization. But in the future, part of global manufacturing may change from centralized to distributed due to 3D printing. To evaluate its impact, this research established a system dynamics model of sneakers supply chain firstly. The modeling showed that the total demand of international transport would decline after the application of 3D printing. For consumer country, the return of manufacturing would increase its container business. And that of producer country would reduce correspondingly. But for resource country, its resource exports would decline, while its container business may grow for the local processing of printing filaments. Secondly, the evaluations based on the data of Guangzhou port suggest that the 3D printing of sneakers was not enough to subvert the existing system. It would be broken only after the 3D printing of electrical products. By then, more manufacturing activities would transfer to the end of supply chain. On the other hand, producer country may actively respond to maintain its advantage in incumbent industrial pattern, such as Belt and Road initiative proposed by China. Deglobalization, caused by 3D printing, and globalization strengthening, caused by trade cooperation, will affect this system simultaneously.

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Ballistic Target PHD Filter Based on Infrared Focal Plane Ambiguous Observation

Space-based early warning system, the main detection means of which is passive detection based on focal plane, is an important part of ballistic missile defense system. The focal plane is mainly composed of CCD, and its size can reach the micron level, so the pixel is often regarded as point of no area in image postprocessing. The design of traditional tracking methods is based on this, and the observation based on the focal plane is modeled as the azimuth with random noise. However, this modeling is inaccurate. In the context of space-based detection, CCD cannot be simplified as a point, and its size should be considered. And the corresponding observation cannot be treated as azimuth with random noise. In this paper, the observation based on focal plane is modeled as Unambiguously Generated Ambiguous (UGA) measurement. The PHD filter algorithm is redesigned and simplified. The simulation results show that the algorithm based on UGA measurement observation model has better tracking effect compared with that based on traditional observation model. This method provides technical support for more accurate target tracking for space-based early warning system.

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Repigmentation of Tenacious Vitiligo on Apremilast

Vitiligo is a common pigment disorder characterized by acquired loss of function or absence of melanocytes, leading to distinct areas of depigmentation. Physical exam reveals sharply demarcated, depigmented macules or patches on otherwise normal skin. Vitiligo can present at any age, in any skin color. There is no specific serologic marker for diagnosis, but patients often have other autoimmune problems. Treatment options are limited and are difficult given the fact that the pathogenesis of the disease is not well elucidated. We present the case of a 52-year-old woman with vitiligo for over 2 decades. The patient’s medical history reveals a lack of response to many different approaches. This case highlights the ability of apremilast, an FDA-approved drug for the treatment of psoriasis and psoriatic arthritis, to achieve repigmentation in a case a vitiligo that has been extremely recalcitrant.

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Invasive Candida Infection after Upper Gastrointestinal Tract Surgery for Gastric Cancer

Upper gastrointestinal tract (GIT) surgical procedures are more likely to cause nosocomial Candida peritonitis than lower GIT procedures and they thus constitute an independent risk factor for mortality. Because of the severity of postsurgical fungal infections complications, intensivists and surgeons need to be extremely aware of their clinical importance in critically ill postsurgical intensive care unit (ICU) patients. We analyzed the clinical and microbiological data of 149 oncologic patients who were hospitalized in the ICU at Soroka Medical Center between January 2010 and January 2015 after undergoing upper GIT surgery for gastric cancer. Invasive fungal infections related to secondary peritonitis following oncologic upper GIT surgery had a higher mortality rate than patients with nonfungal postoperative infectious complications. The presence of gastroesophageal junction leakage and advanced age were found to be independent risk factors for invasive fungal infection after oncologic upper GIT surgery.

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Exponential Stability of Traveling Waves for a Reaction Advection Diffusion Equation with Nonlinear-Nonlocal Functional Response

The stability of a reaction advection diffusion equation with nonlinear-nonlocal functional response is concerned. By using the technical weighted energy method and the comparison principle, the exponential stability of all noncritical traveling waves of the equation can be obtained. Moreover, we get the rates of convergence. Our results improve the previous ones. At last, we apply the stability result to some real models, such as an epidemic model and a population dynamic model.

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Cation-Specific Effects on the Self-Assembly of Collagen Molecules Mediated by Acetate on Mica Surface Observed with Atomic Force Microscopy

The well-organized collagen layers on mica surface have drawn extensive attention for its essential applications and studies on the process of self-assembly as a model system. In this work, collagen extracted from fish scales by acid-base method was used to explore the self-assembly characters, and atomic force microscopy was applied to observe the collagen assembled on mica surface mediated by acetate with four different cations, including K+, Na+, Mg2+, and Ca2+. It showed that cations might influence the interaction between collagen fibrils and mica surface at high ionic concentration. And a similar network structure was acquired with uniform pore size for four kinds of acetates; nearly ranged collagen fibrils in the same direction were collected in Mg2+ solutions, while flat films with some fibrils were achieved in K+ solutions. The Hofmeister series and Collins’ model were adapted to explain the effects of cations and acetate on the self-assembly of collagen. These results and analysis would be helpful for directing the pattern of collagen assembly on a solid surface with a potential application in food science and engineering.

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Tracking Nonlinear Correlation for Complex Dynamic Systems Using a Windowed Error Reduction Ratio Method

Studying complex dynamic systems is usually very challenging due to limited prior knowledge and high complexity of relationships between interconnected components. Current methods either are like a “black box” that is difficult to understand and relate back to the underlying system or have limited universality and applicability due to too many assumptions. This paper proposes a time-varying Nonlinear Finite Impulse Response model to estimate the multiple features of correlation among measurements including direction, strength, significance, latency, correlation type, and nonlinearity. The dynamic behaviours of correlation are tracked through a sliding window approach based on the Blackman window rather than the simple truncation by a Rectangular window. This method is particularly useful for a system that has very little prior knowledge and the interaction between measurements is nonlinear, time-varying, rapidly changing, or of short duration. Simulation results suggest that the proposed tracking approach significantly reduces the sensitivity of correlation estimation against the window size. Such a method will improve the applicability and robustness of correlation analysis for complex systems. A real application to environmental changing data demonstrates the potential of the proposed method by revealing and characterising hidden information contained within measurements, which is usually “invisible” for conventional methods.

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Study of the Optical Properties of Functionalized Gold Nanoparticles in Different Tissues and Their Correlation with the Temperature Increase

Mie theory explains the interaction of light with a gold nanoparticle (AuNP) through the absorption , scattering , and extinction cross sections. These parameters have been calculated in the case of AuNPs dispersed in homogeneous media, but not for specific tissues. The aim of this research was to theoretically obtain the optical cross sections (,, and ) of functionalized AuNPs in liver and colon tissues through Mie theory and correlate them with the temperature increase observed experimentally in tissues containing AuNPs under plasmonic photothermal irradiation using a Nd-YAG laser (λ = 532 nm). Calculations showed that represents % of at 532 nm. The value for a functionalized AuNP in water was 365.66 nm2 (94% of the theoretical maximum value at 522.5 nm), 404.24 nm2 in colon (98% of the theoretical maximum value at 525 nm), and 442.39 nm2 in liver (96% of the theoretical maximum value at 525 nm). Therefore, nanoparticles irradiated at 532 nm are very close to their resonance value. These results correlated with the experimental irradiation of functionalized AuNPs in different tissues, where the average temperature increase showed the pattern liver > colon > water. The temperature increase observed ( up to 13°C) is sufficient to produce cellular death.

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Design, Analysis, and Experiment for Rescue Robot with Wheel-Legged Structure

A wheel-legged rescue robot design with strong environmental adaptability is proposed. The design presented is aimed at helping rescue workers complete their missions, such as environmental and personnel search, quickly and accurately. So it has broad application prospects. In order to achieve the advantages of simple structure, easy control, small occupation space, and wide motion range, a wheel-legged rescue robot is designed in this paper, and the robot can realize three kinds of motion states, which include wheel state, rotation center lifting process, and leg state. Then the motion states are analyzed in detail, which provides a reference for motion control. Considering the wheel state and leg state share the same structure to contact with the ground, the effect of the stiffness of wheel-legged structure to the motion performance is analyzed. Then the experiment is carried out to prove the feasibility of the structure design. This study offers a design and quantitative analysis for wheel-legged rescue robot. Furthermore, a basis for future control research and engineering applications is established.

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Inflammation, Immunity, and Cancer

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A Parkinson's disease gene, DJ-1, repairs brain injury through Sox9 stabilization and astrogliosis

Abstract

Defects in repair of damaged brain accumulate injury and contribute to slow-developing neurodegeneration. Here, we report that a deficiency of DJ-1, a Parkinson's disease (PD) gene, delays repair of brain injury due to destabilization of Sox9, a positive regulator of astrogliosis. Stereotaxic injection of ATP into the brain striatum produces similar size of acute injury in wild-type and DJ-1-knockout (KO) mice. However, recovery of the injury is delayed in KO mice, which is confirmed by 9.4T magnetic resonance imaging and tyrosine hydroxylase immunostaining. DJ-1 regulates neurite outgrowth from damaged neurons in a non-cell autonomous manner. In DJ-1 KO brains and astrocytes, Sox9 protein levels are decreased due to enhanced ubiquitination, resulting in defects in astrogliosis and glial cell-derived neurotrophic factor/ brain-derived neurotrophic factor expression in injured brain and astrocytes. These results indicate that DJ-1 deficiency causes defects in astrocyte-mediated repair of brain damage, which may contribute to the development of PD.

Main Points

• A DJ-1 deficiency decreased Sox9 protein expression in astrocytes by ubiquitination, resulting in defects in astrogliosis and growth factor production, which in turn led to delay in repair of brain injury.

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Retracted: Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis

Following on from the Expression of Concern (10.1002/glia.22466) previously published by GLIA, the following Original Article has been retracted by the journal Editors and Publisher:

Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis

By Milena Penkowa and Juan Hidalgo

GLIA (2000), 32(3), 247–263

DOI: 10.1002/1098–1136(200012)32:3<247::AID-GLIA50>3.0.CO;2-T

Discrepancies in the type and number of animals used in experiments performed by Milena Penkowa and reported in Table 1, identified during the course of investigations into Ms Penkowa's research, render the data and conclusions drawn from them unreliable.

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Downregulation of spinal astrocytic connexin43 leads to upregulation of interleukin-6 and cyclooxygenase-2 and mechanical hypersensitivity in mice

Abstract

Connexin43 (Cx43), involved in intercellular signaling, is expressed in spinal dorsal horn astrocytes and crucial in the maintenance of neuropathic pain. Downregulation of spinal astrocytic Cx43 in mice enhances glutamatergic neurotransmission by decreasing glutamate transporter GLT-1 expression, resulting in cutaneous hypersensitivity. Decreased expression of astrocytic Cx43 could lead to altered expression of other nociceptive molecules. Transfection of Cx43-targeting siRNA in cultured spinal astrocytes increased expression of the pronociceptive cytokine interleukin-6 (IL-6) and the prostaglandin synthesizing enzyme cyclooxygenase-2 (COX-2). Increased expression of IL-6 and COX-2 was due to decreased Cx43 expression rather than due to diminished Cx43 channel function. In mice, downregulation of spinal Cx43 expression by intrathecal treatment with Cx43-targeting siRNA increased IL-6 and COX-2 expression and induced hind paw mechanical hypersensitivity. Cx43 siRNA-induced mechanical hypersensitivity was attenuated by intrathecal treatment with anti-IL-6 neutralizing antibody and intraperitoneal treatment of selective COX-2 inhibitor celecoxib, demonstrating that these molecules play a role in nociceptive processing following Cx43 downregulation. Restoring spinal Cx43 by intrathecal injection of an adenovirus vector expressing Cx43 in mice with a partial sciatic nerve ligation reduced spinal IL-6 and COX-2 expression. Suppression of glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, prevented upregulation of IL-6 and COX-2 expression induced by Cx43 downregulation in both cultured astrocytes and in mouse spinal dorsal horn. Inhibition of spinal GSK-3β also ameliorated Cx43 siRNA-induced mechanical hypersensitivity. The current findings indicate that downregulation of spinal astrocytic Cx43 leads to changes in spinal expression of pronociceptive molecules underlying the maintenance of pain following nerve injury.

Main Points

• Downregulation of connexin 43 (Cx43) gap junctions in spinal astrocytes induces neuropathic pain through upregulation of pro-nociceptive molecules.
• Alteration of spinal Cx43 expression could be crucial in the maintenance of the neuropathic pain state.

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Validation of the online prediction tool PREDICT v. 2.0 in the Dutch breast cancer population

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): M.C. van Maaren, C.D. van Steenbeek, P.D.P. Pharoah, A. Witteveen, G.S. Sonke, L.J.A. Strobbe, P.M.P. Poortmans, S. Siesling
BackgroundPREDICT version 2.0 is increasingly used to estimate prognosis in breast cancer. This study aimed to validate this tool in specific prognostic subgroups in the Netherlands.MethodsAll operated women with non-metastatic primary invasive breast cancer, diagnosed in 2005, were selected from the nationwide Netherlands Cancer Registry (NCR). Predicted and observed 5- and 10-year overall survival (OS) were compared for the overall cohort, separated by oestrogen receptor (ER) status, and predefined subgroups. A >5% difference was considered as clinically relevant. Discriminatory accuracy and goodness-of-fit were determined using the area under the receiver operating characteristic curve (AUC) and the Chi-squared-test.ResultsWe included 8834 patients. Discriminatory accuracy for 5-year OS was good (AUC 0.80). For ER-positive and ER-negative patients, AUCs were 0.79 and 0.75, respectively. Predicted 5-year OS differed from observed by −1.4% in the entire cohort, −0.7% in ER-positive and −4.9% in ER-negative patients. Five-year OS was accurately predicted in all subgroups.Discriminatory accuracy for 10-year OS was good (AUC 0.78). For ER-positive and ER-negative patients AUCs were 0.78 and 0.76, respectively. Predicted 10-year OS differed from observed by −1.0% in the entire cohort, −0.1% in ER-positive and −5.3 in ER-negative patients. Ten-year OS was overestimated (6.3%) in patients ≥75 years and underestimated (−13.%) in T3 tumours and patients treated with both endocrine therapy and chemotherapy (−6.6%).ConclusionsPREDICT predicts OS reliably in most Dutch breast cancer patients, although results for both 5-year and 10-year OS should be interpreted carefully in ER-negative patients. Furthermore, 10-year OS should be interpreted cautiously in patients ≥75 years, T3 tumours and in patients considering endocrine therapy and chemotherapy.



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Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Birgit Geoerger, Christophe Bergeron, Lia Gore, Leonard Sender, Ira J. Dunkel, Cynthia Herzog, Lieve Brochez, Ofelia Cruz, Karsten Nysom, Elmer Berghorn, Burcin Simsek, Jun Shen, Alberto Pappo
BackgroundIpilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available.MethodsPatients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV malignant melanoma received ipilimumab 3 or 10 mg/kg every 3 weeks. Primary end-points were 1-year overall survival and safety.ResultsOver a period of 3.5 years, 12 patients received ipilimumab at either 3 mg/kg (n = 4) or 10 mg/kg (n = 8). The median number of ipilimumab doses was four for 3 mg/kg and three for 10 mg/kg. At 1 year, three of four patients on 3 mg/kg and five of eight patients on 10 mg/kg were alive. Two patients on 10 mg/kg had partial response, and one on 3 mg/kg had stable disease. One patient had durable partial response at 3 years without further treatment, at time of this report. There was one grade 3/4 immune-mediated adverse reaction with 3 mg/kg and five with 10 mg/kg. There were no treatment-related deaths. The study was stopped due to slow accrual.ConclusionsAt >1 year follow-up, ipilimumab demonstrated activity in melanoma patients aged 12 to <18 years, with a similar safety profile as that seen in adults. Our trial highlights the difficulties of enrolling younger patients with rare diseases in clinical trials for treatments that are approved in adults, suggesting adolescents with cancer types occurring predominantly in adults should be considered for inclusion in adult trials of promising new drugs.Clinical trial registration: NCT01696045.



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The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): R.A. Anderson, J. Mansi, R.E. Coleman, D.J.A. Adamson, R.C.F. Leonard
AimChemotherapy results in permanent loss of ovarian function in some premenopausal women. Accurate identification in women with hormone-sensitive early breast cancer (eBC) would allow optimisation of subsequent endocrine treatment. We sought to assess whether analysis of anti-Müllerian hormone (AMH) using a sensitive automated assay could identify women who would not regain ovarian function after chemotherapy.MethodsData from women in the Ovarian Protection Trial in Premenopausal Breast Cancer Patients (OPTION) trial of goserelin (a gonadotrophin-releasing hormone (GnRH) analogue) for ovarian protection were analysed. Women were assessed for premature ovarian insufficiency (POI: amenorrhoea with elevated follicle-stimulating hormone (FSH)) at 24 months after diagnosis. The accuracy of AMH for the diagnosis of POI and its prediction from measurement at the end of chemotherapy was calculated.ResultsAMH below the level of detection showed good diagnostic accuracy for POI at 24 months (n = 73) with receiver operating characteristic (ROC) area under the curve of 0.86, sensitivity 1.0 and specificity 0.73 at the assay limit of detection. In women aged >40 at diagnosis who did not receive goserelin, AMH measured at end of chemotherapy also gave good prediction of POI at 24 months (area under the curve (AUC) 0.89 95% CI 0.75–1.0, n = 32), with sensitivity 0.91, specificity 0.82, diagnostic odds ratio (DOR) 42.8. FSH gave slightly lower AUC, and specificity was low at 0.55. Age but not tamoxifen impacted on AMH levels.ConclusionUsing this sensitive AMH assay, the finding of an undetectable AMH level in women aged >40 at the end of chemotherapy for eBC gave a good prediction that ovarian function would not return. This may allow alterations in post-chemotherapy endocrine management.



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Phase II, multicentre, randomised trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy in patients with HER2-negative metastatic breast cancer

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Yeon Hee Park, Seock-Ah Im, Sung-Bae Kim, Joo Hyuk Sohn, Keun Seok Lee, Yee Soo Chae, Ki Hyeong Lee, Jee Hyun Kim, Young-Hyuck Im, Ji-Yeon Kim, Tae-Yong Kim, Kyung-Hun Lee, Jin-Hee Ahn, Gun Min Kim, In Hae Park, Soo Jung Lee, Hye Sook Han, Se Hyun Kim, Kyung Hae Jung
BackgroundPaclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel.Patients and methodsThis study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC. We hypothesised that EG chemotherapy would not be inferior to PG chemotherapy. The primary end-point was progression-free survival (PFS), which was estimated to be 70% at 6 months for each arm. The secondary end-points were as follows: OS, neuropathic scale, toxicity and clinical benefit rate.ResultsA total of 118 patients (median age: 50, 24–66) were enrolled between March 2015 and March 2016 and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. The mean number of metastatic sites was 3 (range 1–8). The 6-month PFS rates for both arms were 72% for EG and 73% for PG (P = 0.457). There was no significant difference in OS between the two groups (not reached versus 21.2 months, P = 0.2234). The median number of chemotherapy cycles for both groups was 10 for EG and 8 for PG (range 2–32). Clinical benefit rates were 44% for EG and 49% for PG. Major toxicities were neutropenia and neurotoxicity. Grade II or above neurotoxicity was more common with PG than with EG (13.6% for EG versus 45.8% for PG, P < 0.0001).ConclusionEG chemotherapy had similar clinical benefits to PG chemotherapy in terms of PFS but less neurotoxicity.Trial registrationKCSG BR13-11; ClinicalTrials.gov, NCT02263495.



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Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): N. Basset-Séguin, A. Hauschild, R. Kunstfeld, J. Grob, B. Dréno, L. Mortier, P.A. Ascierto, L. Licitra, C. Dutriaux, L. Thomas, N. Meyer, B. Guillot, R. Dummer, P. Arenberger, K. Fife, A. Raimundo, E. Dika, N. Dimier, A. Fittipaldo, I. Xynos, J. Hansson
BackgroundThe SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib—a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)—in a patient population representative of clinical practice. Primary analysis data are presented.Patients and methodsPatients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points.ResultsEvaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0–44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7–71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6–48.1) in patients with metastatic BCC.ConclusionsThe primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control.ClinicalTrials.govNCT01367665.



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Cognitive decline after major oncological surgery in the elderly

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): M. Plas, E. Rotteveel, G.J. Izaks, J.M. Spikman, H. van der Wal-Huisman, B. van Etten, A.R. Absalom, M.J.E. Mourits, G.H. de Bock, B.L. van Leeuwen
BackgroundElderly patients undergoing oncological surgery experience postoperative cognitive decline. The aims of this study were to examine the incidence of cognitive decline 3 months after surgery and identify potential patient-, disease- and surgery-related risk factors for postoperative cognitive decline in onco-geriatric patients.MethodsA consecutive series of elderly patients (≥65 years) undergoing surgery for the removal of a solid tumour were included (n = 307). Cognitive performance was assessed pre-operatively and 3 months postoperatively. Postoperative decline was defined as a decline in scores of cognitive tests of ≥25% on ≥2 of 5 tests.ResultsOf the patients who had completed the assessments, 117 (53%, 95% confidence interval [CI]: 47–60) had improved cognitive test scores, whereas 26 (12%, 95% CI: 7.6–16) showed cognitive decline at 3 months postoperatively. In patients aged >75 years, the incidence of overall cognitive decline 3 months postoperatively was 18% (95% CI: 9.3–27). In patients with lower pre-operative Mini–Mental State Examination (MMSE) score (≤26) the incidence was 37% (95% CI: 18–57), and in patients undergoing major surgery it was 18% (95% CI: 10.6–26). Of the cognitive domains, executive function was the most vulnerable to decline.ConclusionAbout half of the elderly patients show improvement in postoperative cognitive performance after oncological surgery, whereas 12% show cognitive decline. Advanced age, lower pre-operative MMSE score and major surgery are risk factors for cognitive decline at 3 months postoperatively and should be taken into account in the clinical decision-making progress. Research to develop interventions to preserve quality of life should focus on this high-risk subpopulation.



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Very early response of circulating tumour–derived DNA in plasma predicts efficacy of nivolumab treatment in patients with non–small cell lung cancer

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Yuki Iijima, Yosuke Hirotsu, Kenji Amemiya, Yoshihiko Ooka, Hitoshi Mochizuki, Toshio Oyama, Takahiro Nakagomi, Yoshinori Uchida, Yoichi Kobayashi, Toshiharu Tsutsui, Yumiko Kakizaki, Taichiro Goto, Yoshihiro Miyashita, Masao Omata
IntroductionImmunotherapy has become a treatment option for lung cancer. The utility of nivolumab as second-line treatment for non–small cell lung cancer has been proven, but predictive biomarkers influencing its efficacy remain unknown.MethodsThis study involved 14 patients who were treated with nivolumab from February 1 to September 30, 2016. The early response of the level of circulating tumour DNA (ctDNA) after starting nivolumab was evaluated to ascertain whether it could predict treatment outcome.ResultsOf the 14 patients, six were responders and eight were non-responders. DNA was analysed in both tumour tissue and plasma samples. Only somatic mutations confirmed by analysis of tumour tissue were defined as ctDNA. ctDNA was detected more often in the serial plasma samples of patients with high tumour volume (TV) (p = 0.02). ctDNA was detected in seven cases; basal and serial ctDNA analysis revealed that a decrease in allelic frequency (AF) of ctDNA showed high-level correspondence with a good durable response. When “2 weeks” was set as a clinically significant time point, changes in representative mutations of each case, defined as one of the highest baseline AF, showed 100% concordance with the response.ConclusionsIn patients with high TV, plasma analysis of ctDNA, as validated by tumour tissue, suggested that a durable good response to nivolumab could be predicted within 2 weeks.



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Is initial excision of cutaneous melanoma by General Practitioners (GPs) dangerous? Comparing patient outcomes following excision of melanoma by GPs or in hospital using national datasets and meta-analysis

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Peter Murchie, Edwin Amalraj Raja, David H. Brewster, Lisa Iversen, Amanda J. Lee
BackgroundMelanomas are initially excised in primary care, and rates vary internationally. Until now, there has been no strong evidence one way or the other that excising melanomas in primary care is safe or unsafe. European guidelines make no recommendations, and the United Kingdom (UK) melanoma guidelines require all suspicious skin lesions to be initially treated in secondary care based on an expert consensus, which lacks supporting evidence, that primary care excision represents substandard care. Despite this, studies have found that up to 20% of melanomas in the UK are excised by general practitioners (GPs). Patients receiving primary care melanoma excision may fear that their care is substandard and their long-term survival threatened, neither of which may be justified.MethodsScottish cancer registry data from 9367 people diagnosed with melanoma in Scotland between 2005 and 2013 were linked to pathology records, hospital data and death records. A Cox proportional hazards regression analysis, adjusting for key confounders, explored the association between morbidity and mortality and setting of primary melanoma excision (primary versus secondary care). A pooled estimate of the relative hazard of death of having a melanoma excised in primary versus secondary care including 7116 patients from a similar Irish study was also performed.ResultsThe adjusted hazard ratio (95% CI) of death from melanoma for those having primary care excision was 0.82 (0.61–1.10). Those receiving primary care excision had a median (IQR) of 8 (3–14) out-patient attendances compared to 10 (4–17) for the secondary care group with an adjusted relative risk (RR) (95% CI) of 0.98 (0.96–1.01). Both groups had a median of 1 (0–2) hospital admissions with an adjusted rate ratio of 1.05 (0.98–1.13). In the meta-analysis, with primary care as the reference, the pooled adjusted hazard ratio (HR, 95% CI) was 1.26 (1.07–1.50) indicating a significantly higher all-cause mortality among those with excision in secondary care.ConclusionsThe results of the Scottish and pooled analyses suggest that those receiving an initial excision for melanoma in primary care do not have poorer survival or increased morbidity compared to those being initially treated in secondary care. A randomised controlled trial to inform a greater role for GPs in the initial excision of melanoma is justified in the light of these results.



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Rückkaufvereinbarungen und “contra proferentem”-Regel unter dem UN-Kaufrecht

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Cost and Burden of Proof under the CISG – A Discussion amongst Experts

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Zur historischen Auslegung sekundären Gemeinschaftsrechts und deren Grenzen am Beispiel der Produkthaftungsrichtlinie: Entscheidungsanmerkung zu EuGH, Urteil vom 10.1.2006 - C-402/03 (Skov ./. Bilka Lavprisvarehus und Bilka Lavprisvarehus ./. Jette Mikkelsen, Michael Due Nielsen)

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MicroRNA in Glioblastoma: An Overview

Glioblastoma is the most aggressive brain tumor and, even with the current multimodal therapy, is an invariably lethal cancer with a life expectancy that depends on the tumor subtype but, even in the most favorable cases, rarely exceeds 2 years. Epigenetic factors play an important role in gliomagenesis, are strong predictors of outcome, and are important determinants for the resistance to radio- and chemotherapy. The latest addition to the epigenetic machinery is the noncoding RNA (ncRNA), that is, RNA molecules that are not translated into a protein and that exert their function by base pairing with other nucleic acids in a reversible and nonmutational mode. MicroRNAs (miRNA) are a class of ncRNA of about 22 bp that regulate gene expression by binding to complementary sequences in the mRNA and silence its translation into proteins. MicroRNAs reversibly regulate transcription through nonmutational mechanisms; accordingly, they can be considered as epigenetic effectors. In this review, we will discuss the role of miRNA in glioma focusing on their role in drug resistance and on their potential applications in the therapy of this tumor.

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Study reveals large disparities in survival for patients with HPV-associated cancers

A new study found large disparities by sex, race, and age in survival for patients diagnosed with different cancers caused by the human papillomavirus (HPV). Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the...

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Entscheidungsanmerkung zu OLG Frankfurt/M., Urteil vom 13.6.2006 - 8 U 107/03 (Kein Zahlungsverweigerungsrecht mehr nach Wegfall des Staatsnotstands bei argentinischen Staatsanleihen)

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Entscheidungsanmerkung zu BGH, Beschluss vom 3.5.2011 - X ZR 101/11 (Gerichtsstand für Haustürgeschäfte und Streitgenossenschaft bei Anlegerklage gegen Anlagevermittler und Wirtschaftsprüfungsunternehmen)

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Entscheidungsanmerkung zu OLG Köln, Beschluss vom 26.5.2006 - 18 U 78/05 (EuGH-Vorlage zur Rechtzeitigkeit von Zahlungen durch Banküberweisung)

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Entscheidungsanmerkung zu BGH, Urteil vom 1.2.2007 - III ZR 159/06 (Kein Ablauf von sowohl Fälligkeits- als auch Verzugsbeginnfrist an Sonn-/Feiertag)

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Entscheidungsanmerkung zu OLG München, Beschluss vom 6.2.2006 - 34 SchH 10/05 (Beteiligung auch des abgelehnten Schiedsrichters an der Entscheidung über den Ablehnungsantrag)

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Entscheidungsanmerkung zu BGH, Urteil vom 27.11.2007 - X ZR 111/04 (Behandlung eines offenen Kalkulationsirrtums und Verteilung des Absatzrisikos nach UN-Kaufrecht)

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Entscheidungsanmerkung zu BGH, Beschluss vom 11.5.2010 - VIII ZR 212/07 (Gerichtsstand am Erfüllungsort bei grenzüberschreitenden Werklieferungsverträgen, Rechtswahl „deutschen Rechts" im Prozess)

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Entscheidungsanmerkung zu BGH, Urteil vom 11.1.2006 - VIII ZR 268/04 (Rüge eines Rechtsmangels im UN-Kaufrecht unter Angabe des Rechte beanspruchenden Dritten und dessen rechtlicher Schritte)

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Entscheidungsanmerkung zu BGH, Urteil vom 24.4.2013 - XII ZR 10/10 (Keine Beschränkung des europäischen Verbrauchergerichtsstands auf Fernabsatzverträge bei Vertragsanbahnung mittels Internet-Website)

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Entscheidungsanmerkung zu BGH, Urteil vom 26.9.2012 - VIII ZR 100/11 (Eignung der Ware für übliche Zwecke und beiderseitige Schadensverursachung nach UN-Kaufrecht)

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Entscheidungsanmerkung zu BGH, Urteil vom 14.5.2014 - VIII ZR 266/13 (Zum anwendbaren Recht für Aufrechnung gegen Forderung aus internationalem Kauf)

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Doctors should lead the fight against environmental plastics

I welcome Wright and Kelly’s Editorial on the health implications of environmental plastics,1 but I disagree with the conclusion that we need to establish safe thresholds for exposure—the urgent need...

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Nocturnal nasal obstruction is frequent and reduces sleep quality in patients with obstructive sleep apnea

Summary

The prevalence and consequences of nasal obstruction in untreated obstructive sleep apnea patients are not known. The study objectives were to investigate the frequency of subjective and objective nasal obstruction in untreated sleep apnea patients and the associations with sleep and quality of life. Patients in the Icelandic Sleep Apnea Cohort were subjected to a type 3 sleep study, answered questionnaires and had their nasal dimensions measured by acoustic rhinometry. In total, 810 patients participated (including 153 females), aged 54.5 ± 10.6 years [mean ± standard deviation (SD)] with an apnea/hypopnea index 44.7 ± 20.7 h⁻¹. Nocturnal nasal obstruction (greater than or equal to three times per week) was reported by 35% of the patients. These patients had smaller nasal dimensions measured by the minimum cross-sectional area within the smaller nasal valve (0.42 ± 0.17 versus 0.45 ± 0.16 cm², P = 0.013), reported more daytime sleepiness (Epworth Sleepiness Scale score 12.5 ± 4.9 versus 10.8 ± 5.0; P < 0.001) and slightly lower mental quality of life than patients without nocturnal nasal obstruction. Nocturnal nasal obstruction is reported in one-third of the sleep apnea patients and they are more likely to suffer from daytime sleepiness and slightly reduced quality of life than other sleep apnea patients.

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Study of Split-Flow Wall Located at Exit

Congestion is the major cause of crowd stampede-trampling and crushing incidents. To alleviate the phenomenon of congestion in the process of evacuation, theory of split-flow wall is put forward to optimize the evacuation and the principle of it is analyzed. Based on the occupant evacuation software of buildingEXODUS, the set parameters of the split-flow wall are studied, and we find that the best range of shunt wall length is 1.5–2 times the export width and the best position of the split-flow wall is 0.5 to 0.75 times the export width far from the exit. Shunt wall can effectively alleviate and even eliminate the congestion in the process of evacuation and will not affect safe evacuation when crowd density is low.

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Structural Improvements for Tall Buildings under Wind Loads: Comparative Study

The behavior of a very slender building is investigated under wind loads, to satisfy both strength and serviceability (comfort) design criteria. To evaluate the wind effects, wind tunnel testing and structural analysis were conducted, by two different procedures: (i) Pressure Integration Method (PIM), with finite element modeling, and (ii) High Frequency Force Balance (HFFB) technique. The results from both approaches are compared with those obtained from Eurocode 1 and the Italian design codes, emphasizing the need to further deepen the understanding of problems related to wind actions on such type of structure with high geometrical slenderness. In order to reduce wind induced effects, structural and damping solutions are proposed and discussed in a comparative study. These solutions include () height reduction, () steel belts, () tuned mass damper, () viscous dampers, and () orientation change. Each solution is studied in detail, along with its advantages and limitations, and the reductions in the design loads and structural displacements and acceleration are quantified. The study shows the potential of damping enhancement in the building to mitigate vibrations and reduce design loads and hence provide an optimal balance among resilience, serviceability, and sustainability requirements.

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Differentiation between 3,4- and 4,15-Epoxyeudesmanolides by Electrospray Ionization Tandem Mass Spectrometry

We investigated the fragmentation of the eudesmanolide-type sesquiterpene lactones 1α-(4-hydroxymethacryloyloxy)-3α,4α-epoxy-8α-hydroxyeudesm-11(13)-6α,12-olide (1) and 1α-(2,3-epoxyangeloyloxy)-4α,15-epoxy-8α-hydroxyeudesm-11(13)-6α,12-olide (2) by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The elimination of the different ester substituent at C(1) directly from protonated 1 and 2 (A) led to the formation of two regioisomer product ions B (A − RCO2H). Further fragmentation of B resulted from consecutive eliminations of H2O and CO molecules. However, we identified four product ions that allowed for the differentiation between 3,4- and 4,15-epoxyeudesmanolides. The formation of these diagnostic ions was associated with the C(3)–O bond of compound 1, which propitiates the participation of the lone pair of the oxygen epoxide in the formation of B through a Grob-Wharton-type fragmentation, then resulting in an alternative fragmentation pathway. These data can be useful for the fast differentiation between epoxyeudesmanolide regioisomers directly from Dimerostemma extracts by liquid chromatography-tandem mass spectrometry (LC-MS/MS), as an alternative to NMR, or even for quantitation studies of these compounds using multiple reaction monitoring (MRM) scan.

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Need for equity in treatment of substance use among Indigenous people in Canada [Commentary]

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World Medical Association updates ethical code for physicians [News]

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The Cedar Project: mortality among young Indigenous people who use drugs in British Columbia [Research]

BACKGROUND:

Young Indigenous people, particularly those involved in the child welfare system, those entrenched in substance use and those living with HIV or hepatitis C, are dying prematurely. We report mortality rates among young Indigenous people who use drugs in British Columbia and explore predictors of mortality over time.

METHODS:

We analyzed data collected every 6 months between 2003 and 2014 by the Cedar Project, a prospective cohort study involving young Indigenous people who use illicit drugs in Vancouver and Prince George, BC. We calculated age-standardized mortality ratios using Indigenous and Canadian reference populations. We identified predictors of mortality using time-dependent Cox proportional hazard regression.

RESULTS:

Among 610 participants, 40 died between 2003 and 2014, yielding a mortality rate of 670 per 100 000 person-years. Young Indigenous people who used drugs were 12.9 (95% confidence interval [CI] 9.2–17.5) times more likely to die than all Canadians the same age and were 7.8 (95% CI 5.6–10.6) times more likely to die than Indigenous people with Status in BC. Young women and those using drugs by injection were most affected. The leading causes of death were overdose (n = 15 [38%]), illness (n = 11 [28%]) and suicide (n = 5 [12%]). Predictors of mortality included having hepatitis C at baseline (adjusted hazard ratio [HR] 2.76, 95% CI 1.47–5.16), previous attempted suicide (adjusted HR 1.88, 95% CI 1.01–3.50) and recent overdose (adjusted HR 2.85, 95% CI 1.00–8.09).

INTERPRETATION:

Young Indigenous people using drugs in BC are dying at an alarming rate, particularly young women and those using injection drugs. These deaths likely reflect complex intersections of historical and present-day injustices, substance use and barriers to care.

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Physicians and regionalization in Canada: past, present and future [Correction]

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Making the most of the federal investment of $5 billion for mental health [Analysis]

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Feds further limit scope of tax reforms affecting most doctors [News]

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Essential tremor [Practice]

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The authors respond to "Is referral necessary for abnormal bleeding?" [Letters]

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Mechanics hands and hikers feet in antisynthetase syndrome [Practice]

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Mixed news for doctors as feds pivot on tax reforms [News]

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For the world to see Ana [Humanities]

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Health on the hill: Six health bills to watch [News]

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Is referral necessary for abnormal bleeding? [Letters]

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Just get on with improving palliative care, plead experts [News]

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Vinkulierte Namensaktien in der Europäischen Aktiengesellschaft (SE)

Durch die Ausgabe vinkulierter Namensaktien kann eine Gesellschaft sich die Möglichkeit sichern, die Zusammensetzung ihres Aktionärskreises zu kontrollieren. Diese Vinkulierung von Mitgliedschaftsrechten, die bei deutschen Aktiengesellschaften traditionell verbreitet ist, hat in jüngerer Zeit auch für die Societas Europaea (SE) an Bedeutung genwonnen. Der Beitrag erläutert Zweifelsfragen im Zusammenhang mit der Vinkulierungsgestaltung bei der SE und zeigt entsprechende Lösungswege auf. By restricting the transferability of its shares, a company gains the possibility to control who becomes a shareholder. This option, which has traditionally been very popular with German public companies limited by shares, can also be exercised by European Companies (Societas Europaea or SEs). This paper describes the legal possibilities in this area when a SE has its seat in Germany and outlines potential difficulties and solutions.

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Der Richtlinienvorschlag der EU-Kommission zum Vertragsrecht des Online-Warenhandels

Mit ihrem am 09.12.2015 veröffentlichten Richtlinienvorschlag strebt die Kommission eine Vollharmonisierung zentraler Aspekte des Online-Warenhandels und anderer Formen des Fernabsatzes von Waren an, um Unternehmern den grenzüberschreitenden Fernabsatzhandel zu erleichtern und zugleich das Vertrauen der Verbraucher in entsprechende Käufe zu stärken. Die Verfasser vergleichen die Vorgaben des Richtlinienvorschlags mit den geltenden Vorschriften des BGB und gelangen zu einer kritischen Bewertung. Der Vorschlag würde zu einer deutlichen Anhebung des Verbraucherschutzniveaus unter nicht sachgerechter Privilegierung des Fernabsatzhandels gegenüber dem stationären Handel führen; zudem hätte er erhebliche Verwerfungen im Schuldrecht des BGB, insbesondere eine Zersplitterung des Gewährleistungsrechts zur Folge. Unternehmen entstünden dadurch beträchtliche Mehrbelastungen und Anpassungskosten. Gleichzeitig erscheint die Geeignetheit der Richtlinie zur Erreichung ihrer postulierten Ziele fraglich.

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The Modern Travelling Merchant: Mobile Communication in International Contract Law

The use of mobile communication devices like mobile phones, smartphones, tablet computers or notebooks with access to the internet has become an everyday phenomenon in today’s business world. However, whenever mobile communications are used for purposes of contract formation, i.e. the mobile dispatch of offers or acceptances, the mobility of the communicating parties raises important difficulties for the application of traditional legal rules: The fact that messages transmitted via phone, e-mail or SMS can be dispatched and received at virtually any place on earth challenges the categories of private international law and international contract law, which are based on the (unspoken) assumption that parties communicate from their home country. The existing legal framework for cross-border contracts therefore hardly takes into account the possibility that parties may move across borders, and that the place of their communications may accordingly vary. The present article addresses the legal difficulties and uncertainties that cross-border mobile communication raises under international rules of law, covering both conflict of laws rules and substantive law rules. It elaborates on the traditional role of the place of communication in this context before scrutinizing how ‘mobility-friendly’ the provisions of the relevant conventions developed by the United Nations, the Hague Conference for Private International Law and other organisations are. In doing so, it critically discusses in particular Article 10(3) of the UN Electronic Communications Convention of 2005, the most recent attempt at regulating mobile communications. Finally, it identifies a number of problems that have hitherto been overlooked (as notably the interaction of Article 10(3) of the UN Electronic Communications Convention with traditional private international law rules on the formal validity of contracts or with Article 3(2) of the Hague Convention on the Law Applicable to International Sales of Goods of 1955), and proposes appropriate solutions.

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IJMS, Vol. 18, Pages 2339: Midkine and NANOG Have Similar Immunohistochemical Expression Patterns and Contribute Equally to an Adverse Prognosis of Oral Squamous Cell Carcinoma

IJMS, Vol. 18, Pages 2339: Midkine and NANOG Have Similar Immunohistochemical Expression Patterns and Contribute Equally to an Adverse Prognosis of Oral Squamous Cell Carcinoma

International Journal of Molecular Sciences doi: 10.3390/ijms18112339

Authors: Hyun-Min Kim Young-Hoon Kang June-Ho Byun Si-Jung Jang Gyu-Jin Rho Jong-Sil Lee Bong-Wook Park

To increase the overall survival rate and obtain a better prognosis for oral squamous cell carcinoma (OSCC) patients, the detection of more effective and reliable tumor prognostic markers is needed. This study is focused on the analysis of correlation between the clinicopathological features of OSCCs and the immunohistochemical (IHC) expression patterns of MIDKINE (MK) and NANOG. Sixty-two primary OSCC patients were selected and their pretreatment biopsy specimens were immunohistochemically analyzed for the MK and NANOG proteins. The IHC expression patterns, clinicopathological features, and overall survival rates were assessed to identify any correlations. MK and NANOG showed significantly similar IHC expression patterns: both demonstrated enhanced expression in histologically high-grade and clinically late-stage OSCCs. Weak or negative expression of MK and NANOG was correlated with negative neck node metastasis. Clinicopathologically, late tumor stage, neck node metastasis, high-grade tumor, and palliative treatment groups showed significantly lower overall survival rates. The enhanced expression of MK and NANOG was associated with lower overall survival rates. In particular, enhanced co-detection of MK and NANOG showed significant correlation with poor prognosis. In conclusion, enhanced IHC expression patterns of MK and NANOG in OSCC patients was significantly associated with lower overall survival rates and unfavorable clinicopathological features. These results demonstrate that analysis of IHC expression patterns of MK and NANOG in pretreatment biopsy specimens during the work-up period can provide a more definitive prognosis prediction for each OSCC patient that can help clinicians to develop a more precise individual treatment modality.

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IJMS, Vol. 18, Pages 2342: The Molecular and Phenotypic Basis of the Glioma Invasive Perivascular Niche

IJMS, Vol. 18, Pages 2342: The Molecular and Phenotypic Basis of the Glioma Invasive Perivascular Niche

International Journal of Molecular Sciences doi: 10.3390/ijms18112342

Authors: Mohammed Diksin Stuart Smith Ruman Rahman

Gliomas are devastating brain cancers that have poor prognostic outcomes for their patients. Short overall patient survival is due to a lack of durable, efficacious treatment options. Such therapeutic difficulties exist, in part, due to several glioma survival adaptations and mechanisms, which allow glioma cells to repurpose paracrine signalling pathways and ion channels within discreet microenvironments. These Darwinian adaptations facilitate invasion into brain parenchyma and perivascular space or promote evasion from anti-cancer defence mechanisms. Ultimately, this culminates in glioma repopulation and migration at distances beyond the original tumour site, which is a considerable obstacle for effective treatment. After an era of failed phase II trials targeting individual signalling pathways, coupled to our increasing knowledge of glioma sub-clonal divergence, combinatorial therapeutic approaches which target multiple molecular pathways and mechanisms will be necessary for better treatment outcomes in treating malignant gliomas. Furthermore, next-generation therapy which focuses on infiltrative tumour phenotypes and disruption of the vascular and perivascular microenvironments harbouring residual disease cells offers optimism for the localised control of malignant gliomas.

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Coronary resting gradients for hemodynamic lesion assessment - The future of coronary physiology?

Key Points

• Coronary resting gradient measurements with cut-off values of ≤0.87 and ≥0.93 portend a high degree of certainty with respect to appropriateness of coronary revascularization
• Less agreement exists in patients in the so called indeterminate “gray zone”
• Pressure-bounded coronary flow reserve may aid in our understanding of the underlying physiologic principles and facilitate the clinical assessment of these lesions

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