Ruptured Extracranial Carotid Artery: Endovascular Treatment with Covered Stent Graft

Publication date: Available online 20 February 2018
Source:Journal of Neuroradiology
Author(s): Ho Cheol Choi, Sung Eun Park, Dae Seob Choi, Hwa Seon Shin, Ji-Eun Kim, Hye Young Choi, Mi Jung Park, Eun Ha Koh
Background and purposeRupture of the extracranial carotid artery is a rare, but potentially disastrous event. We aimed to review the clinical presentations and radiologic findings of this entity and to evaluate the efficacy of endovascular treatment with covered stent graft.Materials and methodsSince January 2009, eight patients with extracranial carotid artery rupture received endovascular treatment with covered stent graft. We retrospectively reviewed their medical records and radiologic findings.ResultsThe ruptured sites were in the common carotid artery (n = 5), cervical ICA (n = 2) and petrous ICA (n = 1), respectively. The causes of injury included spontaneous (n = 2), carotid blowout syndrome (CBS) (n = 2), iatrogenic (n = 2) and traumatic (n = 2). Technical success and immediate hemostasis were achieved in all cases. Procedure-related complications occurred in 3 patients (37.5%). In a patient, the ipsilateral angular branch of the MCA was occluded during the procedure and it was completely reopened via mechanical thrombectomy without any neurologic deficit. Minor cerebral infarction was developed in 2 patients (25%). During a mean follow-up of 334 days (range 3–2053 days), two patients died: one from recurrent CBS and the other from aspiration pneumonia.ConclusionsThe covered stent grafting is an effective method for the treatment of extracranial carotid artery rupture.



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Newly observed anterior thalamocortical fiber of the thalamus with 7.0T super-resolution magnetic resonance tractogarphy and its implication for the classical Papez circuit

Publication date: Available online 20 February 2018
Source:Journal of Neuroradiology
Author(s): Sang-Han Choi, Young-Bo Kim, Zang-Hee Cho
Here, we have employed recently developed super-resolution tractography using 7.0T-MRI to analyze the fine structures involved in thalamocortical connections, something that has proved difficult using conventional techniques. We detail a newly observed thalamocortical pathway connecting the anterior nucleus of the thalamus and the cingulate cortex not via the internal capsule but via the septal area. The observed pathway is believed to be a classical pathway of the Papez circuit but had not been previously identified.



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Predictors of favorable outcome after mechanical thrombectomy for anterior circulation acute ischemic stroke in octogenarians

Publication date: Available online 20 February 2018
Source:Journal of Neuroradiology
Author(s): Matthias Barral, Louis Lassalle, Cyril Dargazanli, Mikael Mazighi, Hocine Redjem, Raphael Blanc, Georges Rodesch, Bertrand Lapergue, Michel Piotin
IntroductionMechanical thrombectomy for anterior circulation large vessel occlusion (LVO) improves functional outcome at three months. This therapeutic approach is the new gold standard, with a benefit being also observed in elderly patients. However, data are limited in this heterogeneous and fragile population. The objectives of this study were, first, to describe outcome after mechanical thrombectomy in a representative group of patients over 80. Second, to evaluate factors associated with a favorable functional outcome after thrombectomy for anterior circulation LVO in elderly patients (aged≥ 80 years).MethodsA total of 169 patients with anterior circulation LVO referred for an endovascular treatment were included. Primary outcome evaluated functional outcome at three months. Multivariable analysis was performed to identify prognostic factors in elderly patients with pre-stroke mRS≤3.ResultsOverall, 25.34% of patients (43/169) were functionally independent at three months (mRS ≤ 2) and 16.57% (28/169) had a moderate functional disability (mRS = 3). Mortality rate was 33.14% (56/169). At 24h, 7.1% of patients (12/169) had symptomatic hemorrhage. Male gender (p = 0.033), low initial NIHSS (p = 0.037), higher DWI-ASPECTS (p = 0.022) and use of intravenous thrombolysis (IVT) (p=0.0193) were associated with a better functional outcome.ConclusionsThere is no reason to withhold mechanical thrombectomy on the basis of age alone. Small infarct core, low NIHSS, male gender and use of IVT are associated with a better functional outcome.



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Default-Mode Network And Deep Gray-Matter Analysis In Neuromyelitis Optica Patients

Publication date: Available online 20 February 2018
Source:Journal of Neuroradiology
Author(s): Fernanda C Rueda-Lopes, Fernanda M C Pessôa, Gustavo Tukamoto, Fabíola Rachid Malfetano, Simone Batista Scherpenhuijzen, Soniza Alves-Leon, Emerson L Gasparetto
ObjectiveThe aim of our study was to detect functional changes in default-mode network of neuromyelitis optica (NMO) patients using resting-state functional magnetic resonance images and the evaluation of subcortical grey-matter structures volumes.Materials And MethodsNMO patients (n = 28) and controls patients (N=19) were enrolled. We used the integrated registration and segmentation tool, part of FMRIB's Software Library (FSL) to segment subcortical structures including the thalamus, caudate nucleus, putamen, hippocampus and amygdalae. Resting-state functional magnetic resonance images were post-processed using the Multivariate Exploratory Linear Optimized Decomposition into Independent Components, also part of FSL. Average Z-values extracted from the default-mode network were compared between patients and controls using t-tests (p values <0.05 were considered statistically significant).ResultsThere were areas of increased synchronization in the default-mode network of patients compared to controls, notably in the precuneus and right hippocampus (corrected p <0.01). The frontal area had decreased synchronization in patients compared to controls (corrected p <0.01). There were no observed differences between patients and controls in subcortical volumes or average Z-values values for default-mode network.ConclusionThe hyperactivity of certain default-mode network areas may reflect cortical compensation for subtle structural damage in NMO patients.



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Multicenter initial experience with the EmboTrap device in acute anterior ischemic stroke

Publication date: Available online 13 February 2018
Source:Journal of Neuroradiology
Author(s): Bourcier Romain, Abed Diala, Piotin Michel, Redjem Hocine, Ferré Jean Christophe, Eugène François, Raoult Hélène, Mahmood Mirza, Chapot René, Desal Hubert, Nordmeyer Hannes




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The Angiographic and Clinical Outcomes of Intracranial Aneurysms Following Irradiation in Patients with Nasopharyngeal Carcinoma: A 13-year Experience and Literature Review

Publication date: Available online 21 February 2018
Source:Journal of Neuroradiology
Author(s): Chan Siang Hua Victor, Woo Yat Ming Peter, Wong Kai Sing Alain, Chan Kwong Yau, Leung Kar Ming
Background and PurposeIntracranial aneurysms are a known but rare complication of radiotherapy (RT). We reviewed the angiographic and clinical outcomes of intracranial aneurysms following RT in patients with nasopharyngeal carcinoma (NPC), a malignancy endemic in Hong Kong.Materials and MethodsThe clinical, angiographic and laboratory data was collected for nine NPC patients harboring fifteen intracranial aneurysms following RT, diagnosed between 1^st January 2000 and 31^st December 2012.ResultsThe median age at aneurysm diagnosis was 56 years with a male predilection (67%). The median latent period to diagnosis was nine years (0.3 – 30). Eight patients (89%) presented with aneurysmal subarachnoid hemorrhage. Nine aneurysms were located at the anterior circulation, and 14 were saccular in morphology. Of the treated aneurysms, eight underwent endovascular intervention and two were surgically clipped. Within a year, 50% of the treated aneurysms had recurred. Poor neurological outcome was noted. At two-year follow-up, the median score for modified Rankin score and Glasgow Outcome score was 5 and 2 respectively. The two-year mortality rate of patients with treated ruptured intracranial aneurysms was 50%.ConclusionCompared to previous studies, our irradiated NPC patients had higher mortality and morbidity rates after aneurysm rupture and a higher angiographic recurrence rate following treatment. Greater vigilance is required in the detection of post-treatment recurrence of these aneurysms due to the higher risk of rupture. The authors recommend dedicated screening of intracranial aneurysms by active surveillance in routine CT protocols or the addition of three-dimensional time-of-flight magnetic resonance angiography in MR protocols.



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Quantitative analysis in peritumoral volumes of brain metastases treated with stereotactic radiotherapy

Publication date: Available online 2 February 2018
Source:Journal of Neuroradiology
Author(s): Min Soo Kim, Sung Ho Park, Eun Suk Park, Jun Bum Park, Soon Chan Kwon, In Uk Lyo, Hong Bo Sim
PurposeThe purpose of this study was to verify changes in diffusion tensor imaging (DTI) factors in patients with brain metastases treated with stereotactic radiotherapy (SRT). We also investigated the impact of SRT on peritumoral volumes though the use of DTI.MethodsA total of 28 patients with brain metastases who had undergone SRT between March 2014 and December 2015 were enrolled. Magnetic resonance imaging with DTI factors, such as fractional anisotropy (FA) and apparent diffusion tensor (ADC) value, was performed 1 day before the procedure and 3 months after the procedure. DTI data from tumor lesions, edema volumes, and the volumes that received 12Gy were measured.ResultsTumor volume (P=0.001) and ADC values in the volumes that received 12Gy (P=0.018) and the edema volumes (P=0.003) significantly decreased after the procedure. Decreases in tumor volume were only correlated with decreases in edema volumes (P<0.001). Decreases in edema volumes were correlated with increases in FA values and decreases in ADC values of the volumes that received 12Gy [P=0.019 (FA)/0.002 (ADC)] and the edema volumes [P=0.011 (FA)/0.002 (ADC)].ConclusionsIt was possible to quantify changes in peritumoral volumes in patients with brain metastases after SRT by using DTI. ADC values of peritumoral volumes decreased significantly after SRT. Therefore, it was confirmed through DTI that performing SRT on tumor lesions has a positive effect on the structure and function of peritumoral volumes.



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Diagnostic performance of different perfusion algorithms for the detection of angiographical spasm

Publication date: Available online 2 February 2018
Source:Journal of Neuroradiology
Author(s): Saif Afat, Carolin Brockmann, Omid Nikoubashman, Marguerite Müller, Kolja M. Thierfelder, Wolfgang G. Kunz, Ulrike Haberland, Marc A. Brockmann, Konstantin Nikolaou, Martin Wiesmann, Ahmed E. Othman
PurposeTo assess the diagnostic utility of different perfusion algorithms for the detection of angiographical terial spasm.MethodDuring a 2-year period, 45 datasets from 29 patients (54.2±10,75y, 20F) with suspected cerebral vasospasm after aneurysmal subarachnoid hemorrhage were included. Volume Perfusion CT (VPCT), Non-enhanced CT (NCT) and angiography were performed within 6hours post-ictus. Perfusion maps were generated using a maximum slope (MS) and a deconvolution-based approach (DC). Two blinded neuroradiologists independently evaluated MS and DC maps regarding vasospasm-related perfusion impairment on a 3-point Likert-scale (0=no impairment, 1=impairment affecting <50%, 2=impairment affecting >50% of vascular territory). A third independent neuroradiologist assessed angiography for presence and severity of arterial narrowing on a 3-point Likert scale (0=no narrowing, 1=narrowing affecting <50%, 2=narrowing affecting>50% of artery diameter). MS and DC perfusion maps were evaluated regarding diagnostic accuracy for angiographical arterial spasm with angiography as reference standard. Correlation analysis of angiography findings with both MS and DC perfusion maps was additionally performed. Furthermor, the agreement between MS and DC and inter-reader agreement was assessed.ResultsDC maps yielded significantly higher diagnostic accuracy than MS perfusion maps (DC:AUC=.870; MS:AUC=.805; P=0.007) with higher sensitivity for DC compared to MS (DC:sensitivity=.758; MS:sensitivity=.625). DC maps revealed stronger correlation with angiography than MS (DC: R=.788; MS: R=694;=<0.001). MS and DC showed substantial agreement (Kappa=.626). Regarding inter-reader analysis, (almost) perfect inter-reader agreement was observed for both MS and DC maps (Kappa≥981).ConclusionDC yields significantly higher diagnostic accuracy for the detection of angiographic arterial spasm and higher correlation with angiographic findings compared to MS.



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Meningioma assessment: Kinetic parameters in dynamic contrast-enhanced MRI appear independent from microvascular anatomy and VEGF expression

Publication date: Available online 2 February 2018
Source:Journal of Neuroradiology
Author(s): Vera C. Keil, Bogdan Pintea, Gerrit H. Gielen, Kanishka Hittatiya, Angeliki Datsi, Matthias Simon, Rolf Fimmers, Hans H. Schild, Dariusch R. Hadizadeh
Background and purposeKinetic parameters of T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are considered to be largely influenced by microvessel environment. This study was performed to explore the extent of this association for meningiomas.Materials and methodsDCE-MRI kinetic parameters (contrast agent transfer constants K^trans and kep, volume fractions vp and ve) were determined in pre-operative 3T MRI of meningioma patients for later biopsy sites (19 patients; 15 WHO I, no previous radiation, and 4 WHO III pre-radiated recurrent tumors). Sixty-three navigated biopsies were consecutively retrieved. Biopsies were immunohistochemically investigated with endothelial marker CD34 and VEGF antibodies, stratified in a total of 4383 analysis units and computationally assessed for VEGF expression and vascular parameters (vessel density, vessel quantity, vascular fraction within tissue [vascular area ratio], vessel wall thickness). Derivability of kinetic parameters from VEGF expression or microvascularization was determined by mixed linear regression analysis. Tissue kinetic and microvascular parameters were tested for their capacity to identify the radiation status in a subanalysis.ResultsKinetic parameters were neither significantly related to the corresponding microvascular parameters nor to tissue VEGF expression. There was no significant association between microvessel density and its presumed correlate vp (P=0.07). The subgroup analysis of high-grade radiated meningiomas showed a significantly reduced microvascular density (AUC 0.91; P<0.0001) and smaller total vascular fraction (AUC 0.73; P=0.01).ConclusionsIn meningioma, DCE-MRI kinetic parameters neither allow for a reliable prediction of tumor microvascularization, nor for a prediction of VEGF expression. Kinetic parameters seem to be determined from different independent factors.

Graphical abstract

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The Catch Mini Stent Retriever for Mechanical Thrombectomy in distal intracranial occlusions

Publication date: Available online 2 February 2018
Source:Journal of Neuroradiology
Author(s): Jeremy Hofmeister, Zsolt Kulcsar, Gianmarco Bernava, Alain Pellaton, Hasan Yilmaz, Gorislav Erceg, Maria Isabel Vargas, Karl-Olof Lovblad, Paolo Machi
ObjectiveMechanical thrombectomy (MTB) is a treatment of reference for acute ischemic stroke due to large brain vessel occlusion but some concerns remain about its use in small distal branches. In the present study, we assessed the efficacy and the safety of distal MTB using the Catch Mini (CM) stent retriever.MethodsWe retrospectively reviewed a prospectively maintained database of all consecutive patients who underwent MTB for a distal intracranial occlusion with the Catch Mini device at our hospital.ResultsForty-one patient underwent MTB for distal intracranial occlusions using the CM stent retriever. Good capillary reperfusion (TICT≥2b) was observed in 32 out of 41 patients (78%). Focal ischemia within the territory vascularized by the artery addressed by the CM was observed in 8 patients (19.5%). Post-procedural vasospasm was observed in 8 patients, all responding rapidly to vasodilatator administration. Two asymptomatic hemorrhages (4.9%) were noted on follow-up imaging (one patechial hemorrhage and one parenchymal hematoma) in patients with M2 occlusions. No vessel rupture were observed. Overall, good neurological outcome at three months (mRS ≤2) was observed in 28 (out of 34 patients followed; 82,4%) of patients.ConclusionsOur single-center experience shows that the CM stent retriever is safe and effective for the recanalization of small diameter distal branches feeding eloquent brain areas.



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Endovascular recanalization for chronic symptomatic intracranial vertebral artery total occlusion: experience of a single center and review of literature

Publication date: Available online 2 February 2018
Source:Journal of Neuroradiology
Author(s): Peng Gao, Yabing Wang, Yan Ma, Qi Yang, Haiqing Song, Yanfei Chen, Liqun Jiao, Adnan I. Qureshi
ObjectiveThe optimal treatment of chronic symptomatic total occlusion of the intracranial vertebral artery (ICVA) remains undefined. We report a single-center experience of endovascular recanalization for patients with chronic symptomatic ICVA occlusion who were refractory to medical therapy.MethodsFrom Jan 2009 to Jan 2017, we retrospectively reviewed 14 consecutive patients presenting with recurrent symptoms attributed to the chronic ICVA occlusion. We searched previous literature using PubMed databases during the same period as comparison.ResultsEleven patients out of 14 presented initial symptoms to intervention less than 90 days. The occlusion course was extrapolated on simultaneous two-vessel injection angiography or high-resolution MR imaging (HRMRI) in 13 cases. Nine patients had the occlusion beyond the origin of posterior inferior cerebellar artery (PICA) and 5 had the occlusion proximal to the PICA origin. The technical success rate of recanalization was 85.7% (12/14). Two patients (14.3%, 2/14) had peri-procedural complications: 1 developed TIA and 1 presented with perforator occlusion syndrome. Using the keyword-based search, we identified 6 studies at the same period. A total of 34 patients underwent recanalization with the successful recanalization rate at 94.1%, peri-procedural complication rate at 17.6% and mortality at 2.9%, respectively.ConclusionOur single-center study illustrated the feasibility and safety of ICVA recanalization. Great care should be taken as revascularization is of high risk. When patient selection, occlusion course and stage as well as neuroimaging evaluation are considered, endovascular recanalization may be a useful therapeutic modality.



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Trans-venous embolization of a basal ganglia ruptured arteriovenous malformation with open surgical arterial control: a hybrid technique

Publication date: Available online 2 February 2018
Source:Journal of Neuroradiology
Author(s): Zsolt Kulcsár, Paolo Machi, Karl Schaller, Karl Olof Lovblad, Philippe Bijlenga
Treatment of ruptured deep-seated arteriovenous malformations is challenging and associated with elevated risks. This is due to the proximity or involvement of critical brain structures and the specifically fine and delicate angioarchitecture of these lesions, making both endovascular and surgical access technically complicated. We present the advantages of a true combined, open surgical and endovascular transvenous approach in a hybrid operating room. The technique may overcome in part the difficulties and may improve safety and risk related concerns.



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Editorial Board

Publication date: February 2018
Source:Journal of Neuroradiology, Volume 45, Issue 1





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Erratum to “Can a 15s FLAIR replace conventional FLAIR sequence in stroke MR protocols?” [J Neuroradiol 44 (2017) 192–197]

Publication date: February 2018
Source:Journal of Neuroradiology, Volume 45, Issue 1
Author(s): J. Benzakoun, B. Maïer, D. Calvet, M. Edjlali, G. Turc, S. Lion, L. Legrand, W. Ben Hassen, O. Naggara, J.F. Meder, J.L. Mas, C. Oppenheim




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I did NOT feel like this at all before the accident: do men and women report different health and life consequences of a road traffic injury?

Background

Worldwide, injuries represent one of the leading causes of mortality, and nearly one-quarter of all injuries are road traffic related. In many high-income countries, the burden of road traffic injuries (RTIs) has shifted from premature death to injury and disability with long-term consequences; therefore, it is important to assess the full burden of an RTI on individual lives.

Objective

To describe how men and women with minor and moderate injuries reported the consequences of an RTI on their health and lives.

Methods

The study was designed as an explorative qualitative study, in which the answers to an open-ended question concerning the life and health consequences following injury were analysed using systematic text condensation.

Participants

A total of 692 respondents with a minor or a moderate injury were included.

Results

The respondents reported the consequences of the crash on their health and lives according to four categories: physical consequences, psychological consequences, everyday life consequences and financial consequences. The results show that medically classified minor and moderate injuries have detrimental long-term health and life consequences. Although men and women report some similar consequences, there are substantial differences in their reported psychological and everyday life consequences following an injury. Women report travel anxiety and PTSD-like symptoms, being life altering for them compared with men, for whom these types of reports were missing.

Conclusion

These differences emphasise the importance of considering gender-specific physical and psychological consequences following an RTI.

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Gunshot victimisations resulting from high-volume gunfire incidents in Minneapolis: findings and policy implications

Laws restricting large ammunition magazines for semiautomatic weapons are intended to reduce firearm deaths and injuries by preventing gun attacks involving high numbers of shots. However, data on shootings from high-volume gunfire (HVG) incidents are extremely limited. This study examined gunshot victimisations resulting from HVG attacks (>10 shots fired) using police data on shootings in Minneapolis, Minnesota from January through August 2014 (n=135 to 167). Shots fired estimates were generated from police reports based on physical evidence recovered, reported gunshot victims, and accounts of witnesses and actors. HVG incidents accounted for 20%–28% of victims and were more likely to involve multiple victims. Most HVG cases seemed likely to have involved a gun with a large capacity magazine though these data were limited. Restricting large ammunition magazines may have greater potential for preventing shootings than previously estimated, but further studies of this issue are needed.

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New insights into SERCA2a gene therapy in heart failure: pay attention to the negative effects of B-type natriuretic peptides

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial. Moreover, BNP was shown to inhibit SERCA2a expression. Therefore, it is possible that high BNP levels interact with treatment effects of SERCA2a gene transfer and accordingly lead to negative results of CUPID 2 trial. From this point of view, effects of SERCA2a gene therapy should be explored in heart failure with preserved ejection fraction, which is characterised by lower BNP levels compared with HFrEF. In this review, we summarise the current knowledge of SERCA2a gene therapy for heart failure, analyse potential interaction between BNP levels and therapeutic effects of SERCA2a gene transfer and provide directions for future research to solve the identified problems.

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Communication technology and healthcare

EBN Perspectives bring together key issues from the commentaries in one of our nursing topic themes.

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02/23/18 PHD comic: 'Winter Olympics'

Piled Higher & Deeper by Jorge Cham		www.phdcomics.com
title: "Winter Olympics" - originally published 2/23/2018 For the latest news in PHD Comics, CLICK HERE!

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Rapid bupropion-induced hepatotoxicity: a case report and review of the literature

Bupropion is an antidepressant that is also used as a non-nicotine method to aid in smoking cessation. Bupropion-induced hepatotoxicity is quoted to affect between 0.1% and 1% of treated patients with either a...

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Egr-1 Mediated Cardiac miR-99 Family Expression Diverges Physiological Hypertrophy from Pathological Hypertrophy

Publication date: Available online 23 February 2018
Source:Experimental Cell Research
Author(s): Subbiah Ramasamy, Ganesan Velmurugan, Balakrishnan Rekha, Sivakumar Anusha, K Shanmugha Rajan, Suresh Shanmugarajan, Tharmarajan Ramprasath, Pandi Gopal, Dhanendra Tomar, Karuppusamy V Karthik, Suresh Kumar Verma, Venkata Naga Srikanth Garikipati, Rajan Sudarsan
The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99.ConclusionThe results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signalling.

Graphical abstract

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Fasudil inhibits neutrophil-endothelial cell interactions by regulating the expressions of GRP78 and BMPR2

Publication date: Available online 23 February 2018
Source:Experimental Cell Research
Author(s): Jingjing Wang, Jian Xu, Xinyun Zhao, Weiping Xie, Hong Wang, Hui Kong
Regulation of leukocyte-endothelial cell interactions and of vascular permeability plays a critical role in the maintenance of functional pulmonary microvascular barriers. Little is yet known about the effect of the Rho-associated protein kinase (ROCK) inhibitor fasudil on leukocyte-endothelial cell interactions or the underlying mechanism. In the present study, as evaluated using co-culture systems of neutrophils and human pulmonary microvascular endothelial cells (HPMECs), fasudil dose-dependently suppressed neutrophil chemotaxis by decreasing the production of chemotactic factors in lipopolysaccharide (LPS)-treated HPMECs. The inhibitory role of fasudil in neutrophil chemotaxis was mediated by down-regulation of the chaperone glucose-regulated protein 78 (GRP78), since the inhibition was abolished by 4-phenyl butyric acid (a chemical chaperone mimicking GRP78). In addition, fasudil inhibited LPS-induced neutrophil-endothelial adhesion by reducing the expression of intercellular adhesion molecule (ICAM)−1. By use of lentiviral transfection in HPMECs, bone morphogenic protein receptor 2 (BMPR2) overexpression suppressed the LPS-induced increase of both ICAM-1 expression and neutrophil-endothelial adhesion, whereas knocking down BMPR2 abolished the inhibitory role of fasudil in both ICAM-1 expression and neutrophil-endothelial adhesion. Moreover, fasudil alleviated LPS-induced hyperpermeability of HPMEC monolayers by leading to the recovery of intercellular junctions, thereafter reduced neutrophil transendothelial cell migration. Therefore, fasudil inhibited leukocyte-endothelial cell interactions and vascular hyperpermeability through modulation of GRP78 and BMPR2 expression, suggesting a potential role for ROCK as a switch for inhibiting leukocyte-endothelial cell interactions.



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Chronic kidney disease induces inflammation by increasing Toll-like receptor-4, cytokine and cathelicidin expression in neutrophils and monocytes

Publication date: Available online 23 February 2018
Source:Experimental Cell Research
Author(s): Caren C. Grabulosa, Silvia R. Manfredi, Maria E. Canziani, Beata M.R. Quinto, Rodrigo B. Barbosa, Jacqueline F. Rebello, Marcelo C. Batista, Miguel Cendoroglo, Maria A. Dalboni
TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry. Cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 were analyzed via ELISA.TLR4 expression in neutrophils was higher in HD patients than in stage 3 and 4 CKD patients. In these cells, we observed a positive correlation between TLR4 and cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 levels. In monocytes, TLR4 expression was significantly higher in CKD 3 and 4 groups than in the control and HD groups and positively and negatively correlated with IL-6 and MCP-1 and cathelicidin, respectively. TNF-α, IL-6 and MCP-1 serum levels were higher in HD and CKD patients than in control. Cathelicidin and IL-10 levels were only higher in HD patients. IL-6 serum levels were positively correlated with all cytokines, and cathelicidin was negatively correlated with MCP-1 (r = − 0.35; p < 0.01) and positively correlated with IL-10 (r = 0.37; p = 0.001).These results suggest that a uremic environment induces high TLR4, cathelicidin and cytokine expression and may increase inflammation. Thus, future studies should be conducted to evaluate whether TLR4 and cathelicidin should be targets for anti-inflammatory therapeutic strategies.



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Learn how to effectively collaborate with the dentist for the successful BTA treatment of your #cancer patients.… https://t.co/MYA66RV2vw

Learn how to effectively collaborate with the dentist for the successful BTA treatment of your #cancer patients.… https://t.co/MYA66RV2vw

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Targeting strategies of mHealth interventions for maternal health in low and middle-income countries: a systematic review protocol

Introduction

Recently, there has been a steady increase in mobile health (mHealth) interventions aimed at improving maternal health of women in low-income and middle-income countries. While there is evidence indicating that these interventions contribute to improvements in maternal health outcomes, other studies indicate inconclusive results. This uncertainty has raised additional questions, one of which pertains to the role of targeting strategies in implementing mHealth interventions and the focus on pregnant women and health workers as target groups. This review aims to assess who is targeted in different mHealth interventions and the importance of targeting strategies in maternal mHealth interventions.

Methods and analysis

We will search for peer-reviewed, English-language literature published between 1999 and July 2017 in PubMed, Web of Knowledge (Science Direct, EMBASE) and Cochrane Central Registers of Controlled Trials. The study scope is defined by the Population, Intervention, Comparison and Outcomes framework: P, community members with maternal or reproductive needs; I, electronic health or mHealth programmes geared at improving maternal or reproductive health; C, other non-electronic health or mHealth-based interventions; O, maternal health measures including family planning, antenatal care attendance, health facility delivery and postnatal care attendance.

Ethics and dissemination

This study is a review of already published or publicly available data and needs no ethical approval. Review results will be published in a peer-reviewed journal and presented at international conferences.

PROSPERO registration number

CRD42017072280.

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Chinese observational prospective study of ageing population with chronic kidney disease (C-OPTION): a study protocol

Introduction

The proportion of elderly people is steadily rising worldwide, especially in low-income and middle-income countries, including China. Chronic kidney disease (CKD) is a common disorder in older people. However, little is known about the epidemiology of CKD and its consequences among the elderly. Improvements on clinical guidelines and healthcare policies for this population are required. This study aims to examine the risk factors for progression of CKD among the elderly and develop models to identify subgroups who are at high risk.

Methods and analysis

This is a prospective, multicentre, cohort study. The study population comprises ~3000 patients with predialysis CKD, aged ≥65 years, recruited between March 2016 and December 2017. After the baseline assessments, these patients will be followed for 5 years or until the occurrence of primary outcomes. Assessments that include anthropomorphic measures, laboratory tests, questionnaires, and blood and urine specimen collection will be performed at baseline and at follow-ups. Data on demographic information, cognitive function, depression, risk of malnutrition, physical activity and quality of life will be collected. The primary outcomes are incidence of end-stage renal disease, loss of renal function (≥40% decline in glomerular filtration rate from baseline), and death. The secondary outcomes are acute coronary syndrome, hospitalisation for heart failure or unstable angina, cerebrovascular events, and peripheral arterial disease.

Ethics and dissemination

This study protocol has been approved by the ethics committees of the Chinese People’s Liberation Army General Hospital and the participating centres. All the participants gave written informed consent before data collection. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conferences.

Trial registration number

NCT03246204; Pre-results.

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Evaluation of Mediterranean diet adherence scores: a systematic review

Objective

The aim of this review was to evaluate the conceptual suitability, applicability and psychometric properties of scores used internationally to measure adherence to the Mediterranean diet (MD).

Design

This was a systematic review to identify original articles that examined some aspects of the conceptual suitability, applicability or psychometric properties of the MD adherence score. Electronic searches were carried out on the international databases MEDLINE, Scopus, Web of Science and EMBASE (from January 1980 to 31 December 2015).

Eligibility criteria for selecting studies

The study included original articles that examined some aspects of the conceptual suitability, applicability or psychometric properties of the MD adherence score. The studies where MD adherence scores were administered but did not bring forward any evidence about their performance related to conceptual suitability, applicability or psychometric properties were excluded.

Data extraction

Information relating to the scales was extracted in accordance with the quality criteria defined by the Scientific Advisory Committee of the Medical Outcomes Trust for measurement of health results and the quality criteria recommended by Terwee: (1) conceptual, (2) applicability and (3) psychometric properties. Three authors independently extracted information from eligible studies.

Results

Twenty-seven studies were identified as meeting the inclusion criteria, yielding 28 MD adherence scores. The results showed that evidence is scarce and that very few scores fulfilled the applicability parameters and psychometric quality. The scores developed by Panagiotakos et al, Buckland et al and Sotos-Prieto et al showed the highest levels of evidence.

Conclusions

Scores measuring adherence to MD are useful tools for identifying the dietary patterns of a given population. However, further information is required regarding existing scores. In addition, new instruments with greater conceptual and methodological rigour should be developed and evaluated for their psychometric properties.

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Associations between birth weight, obesity, fat mass and lean mass in Korean adolescents: the Fifth Korea National Health and Nutrition Examination Survey

Objective

Previous studies on the relationship between birth weight and obesity in adolescents have mostly been conducted within Western populations and have yielded inconsistent results. We aimed to investigate the association between birth weight, obesity, fat mass and lean mass in Korean adolescents using the fifth Korea National Health and Nutritional Examination Survey (KNHANES V).

Methods

The study population consisted of a total of 1304 (693 men and 611 women) participants aged between 12 and 18 years. Adjusted ORs and 95% CIs were calculated by multivariable logistic regression analyses to determine the association between birth weight and being overweight or obese. Furthermore, adjusted mean values for body mass index (BMI), fat mass index (FMI) and lean mass index (LMI) according to birth weight were calculated by multiple linear regression analyses.

Results

Individuals within the highest 25th percentile in birth weight were more likely to be overweight (adjusted OR (aOR) 1.75, 95% CI 1.11 to 2.76) compared with adolescents within the 25th and 75th percentile in birth weight. Female adolescents who were in the highest 25th percentile in birth weight were more likely to be obese (aOR 2.13, 95% CI 1.03 to 4.41) compared with those within the 25th and 75th percentile in birth weight. Increasing FMI, but not LMI was associated with increasing birth weight (P for trend: 0.03). This tendency remained only in female population in sex-stratified analysis (P for trend: 0.03).

Conclusions

High birth weight may lead to obesity and increased fat mass, but not lean mass. Adolescents born with high birth weight may benefit from close weight monitoring and early intervention against obesity.

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What resources are used in emergency departments in rural sub-Saharan Africa? A retrospective analysis of patient care in a district-level hospital in Uganda

Objectives

To determine the most commonly used resources (provider procedural skills, medications, laboratory studies and imaging) needed to care for patients.

Setting

A single emergency department (ED) of a district-level hospital in rural Uganda.

Participants

26 710 patient visits.

Results

Procedures were performed for 65.6% of patients, predominantly intravenous cannulation, wound care, bladder catheterisation and orthopaedic procedures. Medications were administered to 87.6% of patients, most often pain medications, antibiotics, intravenous fluids, antimalarials, nutritional supplements and vaccinations. Laboratory testing was used for 85% of patients, predominantly malaria smears, rapid glucose testing, HIV assays, blood counts, urinalyses and blood type. Radiology testing was performed for 17.3% of patients, including X-rays, point-of-care ultrasound and formal ultrasound.

Conclusion

This study describes the skills and resources needed to care for a large prospective cohort of patients seen in a district hospital ED in rural sub-Saharan Africa. It demonstrates that the vast majority of patients were treated with a small formulary of critical medications and limited access to laboratories and imaging, but providers require a broad set of decision-making and procedural skills.

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Effectiveness of a complex intervention on Prioritising Multimedication in Multimorbidity (PRIMUM) in primary care: results of a pragmatic cluster randomised controlled trial

Objectives

Investigate the effectiveness of a complex intervention aimed at improving the appropriateness of medication in older patients with multimorbidity in general practice.

Design

Pragmatic, cluster randomised controlled trial with general practice as unit of randomisation.

Setting

72 general practices in Hesse, Germany.

Participants

505 randomly sampled, cognitively intact patients (≥60 years, ≥3 chronic conditions under pharmacological treatment, ≥5 long-term drug prescriptions with systemic effects); 465 patients and 71 practices completed the study.

Interventions

Intervention group (IG): The healthcare assistant conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision support system, the general practitioner optimised medication, discussed it with patients and adjusted it accordingly. The control group (CG) continued with usual care.

Outcome measures

The primary outcome was a modified Medication Appropriateness Index (MAI, excluding item 10 on cost-effectiveness), assessed in blinded medication reviews and calculated as the difference between baseline and after 6 months; secondary outcomes after 6 and 9 months’ follow-up: quality of life, functioning, medication adherence, and so on.

Results

At baseline, a high proportion of patients had appropriate to mildly inappropriate prescriptions (MAI 0–5 points: n=350 patients). Randomisation revealed balanced groups (IG: 36 practices/252 patients; CG: 36/253). Intervention had no significant effect on primary outcome: mean MAI sum scores decreased by 0.3 points in IG and 0.8 points in CG, resulting in a non-significant adjusted mean difference of 0.7 (95% CI –0.2 to 1.6) points in favour of CG. Secondary outcomes showed non-significant changes (quality of life slightly improved in IG but continued to decline in CG) or remained stable (functioning, medication adherence).

Conclusions

The intervention had no significant effects. Many patients already received appropriate prescriptions and enjoyed good quality of life and functional status. We can therefore conclude that in our study, there was not enough scope for improvement.

Trial registration number

ISRCTN99526053. NCT01171339; Results.

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Insulin analogues use in pregnancy among women with pregestational diabetes mellitus and risk of congenital anomaly: a retrospective population-based cohort study

Objectives

To evaluate the risk of major congenital anomaly associated with first-trimester exposure to insulin analogues compared with human insulin in offspring of women with pregestational diabetes.

Design and setting

A population-based cohort of women with pregestational diabetes (n=1661) who delivered between 1996 and 2012 was established retrospectively from seven European regions covered bythe European Surveillance of Congenital Anomalies (EUROCAT) congenital anomaly registries.

Primary outcome measures

The risk of non-chromosomal major congenital anomaly in live births, fetal deaths and terminations for a fetal anomaly exposed to insulin analogues in the first trimester of pregnancy was compared with the risk in those exposed to human insulin only.

Results

During the first trimester, 870 fetuses (52.4%) were exposed to human insulin only, 397 fetuses (23.9%) to insulin analogues only and 394 fetuses (23.7%) to both human insulin and insulin analogues. The risk of major congenital anomaly in fetuses exposed to insulin analogues only was lower than those exposed to human insulin only; the relative risk adjusted for glycaemic control and region was 0.56 (95% CI 0.29 to 1.06). The significantly lower risk related to exposure of insulin analogues only was observed in congenital heart defects: adjusted relative risk 0.14 (95% CI 0.03 to 0.62).

Conclusions

In this retrospective population-based cohort study across Europe, first-trimester exposure to insulin analogues did not increase the risk of major congenital anomaly compared with exposure to human insulin. A possible lower risk of congenital heart defects among fetuses exposed to insulin analogues only deserves further investigation.

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Association between perceived stress, multimorbidity and primary care health services: a Danish population-based cohort study

Objectives

Mental stress is common in the general population. Mounting evidence suggests that mental stress is associated with multimorbidity, suboptimal care and increased mortality. Delivering healthcare in a biopsychosocial context is key for general practitioners (GPs), but it remains unclear how persons with high levels of perceived stress are managed in primary care. We aimed to describe the association between perceived stress and primary care services by focusing on mental health-related activities and markers of elective/acute care while accounting for mental–physical multimorbidity.

Design

Population-based cohort study.

Setting

Primary healthcare in Denmark.

Participants

118 410 participants from the Danish National Health Survey 2010 followed for 1 year. Information on perceived stress and lifestyle was obtained from a survey questionnaire. Information on multimorbidity was obtained from health registers.

Outcome measures

General daytime consultations, out-of-hours services, mental health-related services and chronic care services in primary care obtained from health registers.

Results

Perceived stress levels were associated with primary care activity in a dose–response relation when adjusted for underlying conditions, lifestyle and socioeconomic factors. In the highest stress quintile, 6.8% attended GP talk therapy (highest vs lowest quintile, adjusted incidence rate ratios (IRR): 4.96, 95% CI 4.20 to 5.86), 3.3% consulted a psychologist (IRR: 6.49, 95% CI 4.90 to 8.58), 21.5% redeemed an antidepressant prescription (IRR: 4.62, 95% CI 4.03 to 5.31), 23.8% attended annual chronic care consultations (IRR: 1.22, 95% CI 1.16 to 1.29) and 26.1% used out-of-hours services (IRR: 1.47, 95% CI 1.51 to 1.68). For those with multimorbidity, stress was associated with more out-of-hours services, but not with more chronic care services.

Conclusion

Persons with high stress levels generally had higher use of primary healthcare, 4–6 times higher use of mental health-related services (most often in the form of psychotropic drug prescriptions), but less timely use of chronic care services.

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SecurAstaP trial: securement with SecurAcath versus StatLock for peripherally inserted central catheters, a randomised open trial

Objectives

To assess the effect on needed nursing time for dressing change.

Design, setting, participants

A parallel-group, open-label, randomised controlled trial in patients who are in need for a peripherally inserted central catheter insertion in one teaching hospital in Belgium. The follow-up lasted 180 days or until catheter removal, whatever came first. A computer generated table was used to allocate devices. Randomised patients were 105 adults (StatLock, n=53; SecurAcath, n=52) and primary analysis was based on all patients (n=92) with time measurements (StatLock, n=43; SecurAcath, n=49).

Interventions

StatLock which has to be changed weekly versus SecurAcath which could remain in place for the complete catheter dwell time.

Main outcome measure

Needed time for the dressing change at each dressing change (SecurAcath) or at each dressing change combined with the change of the securement device (StatLock).

Results

Median time needed for dressing change was 7.3 min (95% CI 6.4 min to 8.3 min) in the StatLock group and in the SecurAcath group 4.3 min (95% CI 3.8 min to 4.9 min) (P<0.0001). The time in the SecurAcath group was reduced with 41% (95% CI 29% to 51%). Incidence rates of migration, dislodgement and catheter-related bloodstream infection were comparable across groups. Pain scores were higher with SecurAcath than with StatLock at insertion (P=0.02) and at removal (P<0.001) and comparable during dressing change (P=0.38) and during dwell time (P=0.995). User-friendliness was scored at insertion and removal. All statements regarding the user-friendliness were scored significantly higher for StatLock than for SecurAcath (P<0.05). Only for the statement regarding the recommending routine use of the device, which was asked at removal, no difference was found between the two devices (P=0.32).

Conclusion

Use of SecurAcath saves time during dressing change compared with StatLock. Training on correct placement and removal of SecurAcath is critical to minimise pain.

Trial registration number

NCT02311127; Pre-results.

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Interactive voice response interventions targeting behaviour change: a systematic literature review with meta-analysis and meta-regression

Objective

A number of promising automated behaviour change interventions have been developed using advanced phone technology. This paper reviewed the effectiveness of interactive voice response (IVR)-based interventions designed to promote changes in specific health behaviours.

Methods

A systematic literature review of papers published between January 1990 and September 2017 in MEDLINE, CINAHL, Embase, PsycINFO, SCOPUS and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted. From the total of 2546 papers identified, 15 randomised control trials (RCTs) met the eligibility criteria and were included in a random effects meta-analysis. Meta-regression analysis was used to explore whether behaviour change techniques (BCTs) that were used in the interventions were associated with intervention effectiveness.

Results

Meta-analysis of 15 RCTs showed that IVR-based interventions had small but significant effects on promoting medication adherence (OR=1.527, 95% CI 1.207 to 1.932, k=9, p=0.000) and physical activity (Hedges’ g=0.254, 95% CI 0.068 to 0.439, k=3, p=0.007). No effects were found for alcohol (Hedges’ g=–0.077, 95% CI –0.162 to 0.007, k=4, p=0.073) or diet (Hedges’ g=0.130, 95% CI –0.088 to 0.347, k=2, p=0.242). In the medication adherence studies, multivariable meta-regression including six BCTs explained 100% of the observed variance in effect size, but only the BCT ‘information about health consequences’ was significantly associated with effect size (β=0.690, SE=0.199, 95% CI 0.29 to 1.08, p=0.000).

Conclusion

IVR-based interventions appear promising in changing specific health behaviours, such as medication adherence and physical activity. However, more studies are needed to elucidate further the combination of active components of IVR interventions that make them effective and test their feasibility and effectiveness using robust designs and objective outcome measures.

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Prevalence, causes and mental health impact of workplace bullying in the Neonatal Intensive Care Unit environment

Objectives

The aim of this study is to examine the prevalence, to report barriers and mental health impact of bullying behaviours and to analyse whether psychological support at work could affect victims of bullying in the healthcare workplace.

Design

Self-administered questionnaire survey.

Setting

20 in total neonatal intensive care units in 17 hospitals in Greece.

Participants

398 healthcare professionals (doctors, nurses).

Main outcome measures

The questionnaire included information on demographic data, Negative Act Questionnaire-Revised (NAQ-R) behaviour scale, data on sources of bullying, perpetrators profile, causal factors, actions taken and reasons for not reporting bullying, psychological support and 12-item General Health Questionnaire (GHQ-12) scores to investigate psychological distress.

Results

Prevalence of bullying measured by the NAQ-R was 53.1% for doctors and 53.6% for nurses. Victims of bullying differed from non-bullied in terms of gender and job experience, among demographic data. Crude NAQ-R score was found higher for female, young and inexperienced employees. Of those respondents who experienced bullying 44.9% self-labelled themselves as victims. Witnessing bullying of others was found 83.2%. Perpetrators were mainly females 45–64 years old, most likely being a supervisor/senior colleague. Common reasons for not reporting bullying was self-dealing and fear of consequences. Bullying was attributed to personality trait and management. Those who were bullied, self-labelled as a victim and witnessed bullying of others had higher GHQ-12 score. Moreover, psychological support at work had a favour effect on victims of bullying.

Conclusions

Prevalence of bullying and witnessing were found extremely high, while half of victims did not consider themselves as sufferers. The mental health impact on victims and witnesses was severe and support at work was necessary to ensure good mental health status among employees.

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Is there a role for MR-guided focused ultrasound in Parkinson's disease?

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IJERPH, Vol. 15, Pages 393: Investigation of a Brownfield Conflict Considering the Strength of Preferences

IJERPH, Vol. 15, Pages 393: Investigation of a Brownfield Conflict Considering the Strength of Preferences

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020393

Authors: Jing Yu Ling-Ling Pei

By employing the Graph Model for Conflict Resolution methodology, this paper models and analyzes a brownfield conflict that occurred at the Changzhou Foreign Language School in Jiangsu, China, in 2016. This conflict made national headlines when news reports revealed that a large number of students and staff suffered from health issues after the school moved to a new site that is built on recently restored land adjacent to the original “Chang Long Chemical” block. Since stakeholders in the conflict hold different strengths of preference, a new option prioritization technique is employed to elicit both crisp preferences and the strength of preferences for the decision-makers (DMs) in the conflict. The conflict analysis result is consistent with the actual trajectory of the conflict and provides strategic insights into the conflict. More specifically, equilibrium results suggest that the firm should have been required to thoroughly clean the site, the local government should not have relocated the school, and the environmental agency and other stakeholders should have closely monitored the firm’s activities. In short, strategic insights garnered from this case study indicate that positive interactions should be fostered among the local government, the enterprise, and the public to ensure sustainable brownfield land redevelopment in the future.

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health technology; +256 new citations

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

health technology

These pubmed results were generated on 2018/02/24

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

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Viruses, Vol. 10, Pages 98: Development and Validation of a Novel Dual Luciferase Reporter Gene Assay to Quantify Ebola Virus VP24 Inhibition of IFN Signaling

Viruses, Vol. 10, Pages 98: Development and Validation of a Novel Dual Luciferase Reporter Gene Assay to Quantify Ebola Virus VP24 Inhibition of IFN Signaling

Viruses doi: 10.3390/v10020098

Authors: Elisa Fanunza Aldo Frau Marco Sgarbanti Roberto Orsatti Angela Corona Enzo Tramontano

The interferon (IFN) system is the first line of defense against viral infections. Evasion of IFN signaling by Ebola viral protein 24 (VP24) is a critical event in the pathogenesis of the infection and, hence, VP24 is a potential target for drug development. Since no drugs target VP24, the identification of molecules able to inhibit VP24, restoring and possibly enhancing the IFN response, is a goal of concern. Accordingly, we developed a dual signal firefly and Renilla luciferase cell-based drug screening assay able to quantify IFN-mediated induction of Interferon Stimulated Genes (ISGs) and its inhibition by VP24. Human Embryonic Kidney 293T (HEK293T) cells were transiently transfected with a luciferase reporter gene construct driven by the promoter of ISGs, Interferon-Stimulated Response Element (ISRE). Stimulation of cells with IFN-α activated the IFN cascade leading to the expression of ISRE. Cotransfection of cells with a plasmid expressing VP24 cloned from a virus isolated during the last 2014 outbreak led to the inhibition of ISRE transcription, quantified by a luminescent signal. To adapt this system to test a large number of compounds, we performed it in 96-well plates; optimized the assay analyzing different parameters; and validated the system by calculating the Z′- and Z-factor, which showed values of 0.62 and 0.53 for IFN-α stimulation assay and VP24 inhibition assay, respectively, indicative of robust assay performance.

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HARMless: Transient Cortical and Sulcal Hyperintensity on Gadolinium-Enhanced FLAIR after Elective Endovascular Coiling of Intracranial Aneurysms.

HARMless: Transient Cortical and Sulcal Hyperintensity on Gadolinium-Enhanced FLAIR after Elective Endovascular Coiling of Intracranial Aneurysms.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: Suthiphosuwan S, Hsu CC, Bharatha A

Abstract
BACKGROUND AND PURPOSE: Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR has been increasingly recognized after iodinated contrast medium exposure during angiographic procedures. The goal of this study was to assess the relationship of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR against various variables in patients following elective endovascular treatment of intracranial aneurysms.
MATERIALS AND METHODS: We performed a retrospective review of 58 patients with 62 MR imaging studies performed within 72 hours following endovascular treatment of intracranial aneurysms. Patient demographics, aneurysm location, and vascular territory distribution of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR were documented. Analysis of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated contrast medium volume, procedural duration, number of angiographic runs, and DWI lesions was performed.
RESULTS: Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR was found in 32/62 (51.61%) post-endovascular treatment MR imaging studies, with complete resolution of findings in all patients on the available follow-up studies (27/27). Angiographic iodinated contrast medium injection and arterial anatomy matched the vascular distribution of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR. No significant association was found between cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated contrast medium volume (P = .56 value) and the presence of DWI lesions (P = .68). However, a significant association was found with procedural time (P = .001) and the number of angiographic runs (P = .019). No adverse clinical outcomes were documented.
CONCLUSIONS: Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR is a transient observation in the arterial territory exposed to iodinated contrast medium during endovascular treatment of intracranial aneurysms. Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR is significantly associated with procedural time, and the frequency of angiographic runs suggesting a potential technical influence on the breakdown of the BBB, but no reported adverse clinical outcome or association with both iodinated contrast medium volume and DWI lesions was found. Recognition of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR as a benign incidental finding is vital to avoid unnecessary investigation.

PMID: 29472303 [PubMed - as supplied by publisher]

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Quantification of Intracranial Aneurysm Volume Pulsation with 7T MRI.

Quantification of Intracranial Aneurysm Volume Pulsation with 7T MRI.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: Kleinloog R, Zwanenburg JJM, Schermers B, Krikken E, Ruigrok YM, Luijten PR, Visser F, Regli L, Rinkel GJE, Verweij BH

Abstract
BACKGROUND AND PURPOSE: Aneurysm volume pulsation is a potential predictor of intracranial aneurysm rupture. We evaluated whether 7T MR imaging can quantify aneurysm volume pulsation.
MATERIALS AND METHODS: In Stage I of the study, 10 unruptured aneurysms in 9 patients were studied using a high-resolution (0.6-mm, isotropic) 3D gradient-echo sequence with cardiac gating. Semiautomatic segmentation was used to measure aneurysm volume (in cubic millimeters) per cardiac phase. Aneurysm pulsation was defined as the relative increase in volume between the phase with the smallest volume and the phase with the largest volume. The accuracy and precision of the measured volume pulsations were addressed by digital phantom simulations and a repeat image analysis. In Stage II, the imaging protocol was optimized and 9 patients with 9 aneurysms were studied with and without administration of a contrast agent.
RESULTS: The mean aneurysm pulsation in Stage I was 8% ± 7% (range, 2%-27%), with a mean volume change of 15 ± 14 mm3 (range, 3-51 mm3). The mean difference in volume change for the repeat image analysis was 2 ± 6 mm3. The artifactual volume pulsations measured with the digital phantom simulations were of the same magnitude as the volume pulsations observed in the patient data, even after protocol optimization in Stage II.
CONCLUSIONS: Volume pulsation quantification with the current imaging protocol on 7T MR imaging is not accurate due to multiple imaging artifacts. Future studies should always include aneurysm-specific accuracy analysis.

PMID: 29472302 [PubMed - as supplied by publisher]

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Revenue Increase following 2017 Multiple Procedures Payment Reduction Modification: Differential Impact on Neuroradiology-Report from an Academic Medical Center.

Revenue Increase following 2017 Multiple Procedures Payment Reduction Modification: Differential Impact on Neuroradiology-Report from an Academic Medical Center.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: Noveiry BB, Varzaneh FN, Yousem DM

Abstract
BACKGROUND AND PURPOSE: The Centers for Medicare and Medicaid Services imposed a 25% professional component multiple procedure payment reduction for the professional component of advanced diagnostic imaging modalities in January 2012. In 2017, the Centers for Medicare and Medicaid Services rolled back the multiple procedure payment reduction to 5% for subsequent imaging. To evaluate the effect of this change, we analyzed 5 months of Centers for Medicare and Medicaid Services procedures at Johns Hopkins Medical Institution.
MATERIALS AND METHODS: We analyzed the procedure codes and reimbursement rate for studies performed between January 1 and May 31, 2017. Patients with Medicare insurance who had multiple diagnostic procedures in a day were selected. Per the Centers for Medicare and Medicaid Services guidelines, procedures with the highest price were considered fully reimbursed and subsequent studies were marked for differences between 25% (2013-2016) and 5% reduction (2017).
RESULTS: We included 8787 patients with 22,236 procedures (mean, 2.53 studies/day). CT, MR imaging, and ultrasound scans composed 75.9%, 21.5%, and 2.6% of all studies, with 61.2%, 54.9%, and 85.4% of the procedures of each technique subject to multiple procedure payment reduction, respectively. The projected reimbursement for these studies was $1,666,437, which translated to a $179,782 (12.1%) increase in revenue comparing 25%-versus-5% multiple procedure payment reduction rates for 5 months: $128,542 for CT, $47,802 for MR imaging, and $3439 for ultrasound. The annual overall prorated increase in revenue would be $431,476. The impact was maximal for neuroradiology.
CONCLUSIONS: With the recent favorable adjustment in multiple procedure payment reduction regulations, CT-heavy subspecialties like neuroradiology benefit the most with revenue increases. Different practice settings might experience revenue increases to a different extent, depending on the procedure and payer mix.

PMID: 29472301 [PubMed - as supplied by publisher]

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An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: Dworkin JD, Linn KA, Oguz I, Fleishman GM, Bakshi R, Nair G, Calabresi PA, Henry RG, Oh J, Papinutto N, Pelletier D, Rooney W, Stern W, Sicotte NL, Reich DS, Shinohara RT, North American Imaging in Multiple Sclerosis Cooperative

Abstract
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions.
MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites.
RESULTS: The proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone.
CONCLUSIONS: This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.

PMID: 29472300 [PubMed - as supplied by publisher]

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Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis.

Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: Van Obberghen E, Mchinda S, le Troter A, Prevost VH, Viout P, Guye M, Varma G, Alsop DC, Ranjeva JP, Pelletier J, Girard O, Duhamel G

Abstract
BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer.
MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated.
RESULTS: The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio.
CONCLUSIONS: The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.

PMID: 29472299 [PubMed - as supplied by publisher]

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Sonographic Development of the Pericallosal Vascularization in the First and Early Second Trimester of Pregnancy.

Sonographic Development of the Pericallosal Vascularization in the First and Early Second Trimester of Pregnancy.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: De Keersmaecker B, Pottel H, Naulaers G, De Catte L

Abstract
BACKGROUND AND PURPOSE: Anomalies of the corpus callosum are rare. Routine scanning in midtrimester of the pregnancy often fails to identify defective development. The purpose of the study was to identify the pericallosal artery and all its main branching arteries during early gestation from the first trimester onward, to measure the length of the pericallosal artery during its development, and to establish a normal vascular map for each week of development.
MATERIALS AND METHODS: We performed a single-center prospective, longitudinal clinical study in 15 patients between 11 and 22 weeks of gestation. The origin and course of the different blood vessels were identified.
RESULTS: There was a linear association among gestational age, the biparietal diameter, and the length of the pericallosal artery. The curvature of the developing pericallosal artery increases linearly with the gestational age and biparietal diameter, and 4 variations of branching of the callosomarginal artery were observed.
CONCLUSIONS: The pericallosal artery and its branches can be identified and measured from 11 weeks on, and the pericallosal artery takes its characteristic course. A defective course or an abnormal biometry of the pericallosal artery could be an early sonographic marker of abnormal development of the corpus callosum.

PMID: 29472298 [PubMed - as supplied by publisher]

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Intraoperative Conebeam CT for Assessment of Intracochlear Positioning of Electrode Arrays in Adult Recipients of Cochlear Implants.

Intraoperative Conebeam CT for Assessment of Intracochlear Positioning of Electrode Arrays in Adult Recipients of Cochlear Implants.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: Jia H, Torres R, Nguyen Y, De Seta D, Ferrary E, Wu H, Sterkers O, Bernardeschi D, Mosnier I

Abstract
BACKGROUND AND PURPOSE: Intraoperative conebeam CT has been introduced into the operating room and provides quick radiologic feedback. This study aimed to investigate its utility in the assessment of the positioning of the electrode array after cochlear implantation.
MATERIALS AND METHODS: This was a retrospective study of 51 patients (65 ears) with intraoperative imaging by conebeam CT (O-arm) after cochlear implantation between 2013 and 2017. Correct placement into the cochlea was immediately identified. Positioning assessments were later analyzed with OsiriX software.
RESULTS: Intraoperative imaging was quickly performed in all cases. No misplacement into the vestibule or semicircular canals was found. A foldover of the implanted array was identified in 1 patient. Secondary analysis by 2 raters showed excellent agreement on insertion depth angle (intraclass correlation = 0.96, P < .001) and length of insertion of the electrode array (intraclass correlation coefficient = 0.93, P = .04) measurements. The evaluation of the number of extracochlear electrodes was identical between the 2 raters in 78% of cases (Cohen κ = 0.55, P < .001). The scalar position was inconsistent between raters. When we compared O-arm and high-resolution CT images in 14 cases, the agreement was excellent for insertion depth angle (intraclass correlation coefficient = 0.97, P < .001) and insertion length (intraclass correlation coefficient = 0.98, P < .001), good for the number of extracochlear electrodes (Cohen κ = 0.63, P = .01), but moderate for the scalar position (Cohen κ = 0.59, P = .02).
CONCLUSIONS: Intraoperative conebeam CT using the O-arm is a safe, rapid, easy, and reliable procedure to immediately identify a misplacement or foldover of an electrode array. The insertion depth angle, insertion length, and number of electrodes inserted can be accurately assessed.

PMID: 29472297 [PubMed - as supplied by publisher]

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Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping.

Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping.

AJNR Am J Neuroradiol. 2018 Feb 22;:

Authors: Soman S, Liu Z, Kim G, Nemec U, Holdsworth SJ, Main K, Lee B, Kolakowsky-Hayner S, Selim M, Furst AJ, Massaband P, Yesavage J, Adamson MM, Spincemallie P, Moseley M, Wang Y

Abstract
BACKGROUND AND PURPOSE: Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology.
MATERIALS AND METHODS: Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident.
RESULTS: Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping; they were worse on preconditioned quantitative susceptibility mapping.
CONCLUSIONS: Preconditioned quantitative susceptibility mapping MR imaging can bring the benefits of quantitative susceptibility mapping imaging to clinical practice without the limitations of mask-based quantitative susceptibility mapping, especially for evaluating cerebral microhemorrhage-associated pathologies, such as traumatic brain injury.

PMID: 29472296 [PubMed - as supplied by publisher]

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Additional muscular slip of the flexor digitorum longus muscle to the fifth toe.

Additional muscular slip of the flexor digitorum longus muscle to the fifth toe.

Surg Radiol Anat. 2018 Feb 22;:

Authors: Stimec BV, Dash J, Assal M, Stern R, Fasel JHD

Abstract
Despite the fact that there are numerous reports on muscular variations in the sole of the foot, routine dissection in a formaldehyde-fixed cadaver revealed an accessory flexor digiti quinti muscle, which to the best of our knowledge is a very unusual variant. This was in the form of a slender, 38 mm long muscular slip, with a proximal and distal tendon extending from the common flexor digitorum longus tendinous plate out to the distal phalanx of the fifth toe. An associated finding was the absence of the musculotendinous portion of the flexor digitorum brevis to the same toe. A developmental explanation for this variation is presented. Clinical implications with regard to this anatomical condition may result in clawing of the fifth toe.

PMID: 29473094 [PubMed - as supplied by publisher]

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Adhesion, proliferation, and apoptosis in different molecular portraits of breast cancer treated with silver nanoparticles and its pathway-network analysis

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IJERPH, Vol. 15, Pages 391: Sharply Reduced but Still Heavy Self-Harm Burdens in Hubei Province, China, 1990–2015

IJERPH, Vol. 15, Pages 391: Sharply Reduced but Still Heavy Self-Harm Burdens in Hubei Province, China, 1990–2015

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020391

Authors: Jingju Pan Lan Zhang Yumeng Tang Qian Li Chuanhua Yu Tianjing He

The aims of this study were to describe fatal and non-fatal self-harm burdens, as well as burdens from the main preventable risk factors, and to investigate the different suicide methods in Hubei province in central China utilizing data from both Global Burden of Disease Study 2015 and Hubei Disease Surveillance Points system. All self-harm burdens including mortality, years of life lost (YLLs), prevalence, years lived with disability (YLDs), and disability adjusted life-years (DALYs) consistently demonstrated downward trends in Hubei from 1990 to 2015, with a bigger decline gap observed among females and narrower decreasing amplitudes among the elderly. Hubei experienced much higher age-standardized rates for self-harm mortality (22.0 per 100,000), YLLs (560.1 per 100,000) and DALYs (563.9 per 100,000) than the national (9.0, 292.3 and 295.0 per 100,000 respectively) and global levels (11.5, 453.3 and 457.9 per 100,000 respectively) in 2015. Self-harm burdens have begun shifting from females to males and the elderly suffered more self-harm burdens than other age groups. Alcohol use accounted for 20.9% of all self-harm DALYs for males, whereas intimate partner violence accounted for 24.4% of all self-harm DALYs for females. Poisoning, mainly pesticide self-poisoning, was still the most common method of suicide. Effective interventions by multi-sectoral collaboration are urgently needed to reduce the alarmingly heavy self-harm burdens in Hubei.

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IJERPH, Vol. 15, Pages 392: Preparing Physical and Occupational Therapists to Be Health Promotion Practitioners: A Call for Action

IJERPH, Vol. 15, Pages 392: Preparing Physical and Occupational Therapists to Be Health Promotion Practitioners: A Call for Action

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020392

Authors: David Morris Gavin Jenkins

Experts around the world support the integration of health promotion and wellness (HPW) services into traditional health care services. If successfully executed, the addition of HPW services would reduce rates of death and disability and significantly reduce health care costs. While all health care providers should be engaged in providing HPW services, many believe that physical therapists (PTs) and occupational therapists (OTs) are uniquely positioned to provide these services. However, research suggests that clinicians in both fields may fall short in doing so. Likewise, research indicates that entry-level educational programs inadequately prepare PT and OT students to be HPW practitioners. The overall purpose of this paper is to provide recommendations to educators for preparing PT and OT students and clinicians to better meet the HPW needs of the clients and patients they serve.

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Partial maxillectomy for ameloblastoma of the maxilla with infratemporal fossa involvement: A combined endoscopic endonasal and transoral approach.

Partial maxillectomy for ameloblastoma of the maxilla with infratemporal fossa involvement: A combined endoscopic endonasal and transoral approach.

J Stomatol Oral Maxillofac Surg. 2018 Feb 20;:

Authors: Guha A, Hart L, Polachova H, Chovanec M, Schalek P

Abstract
BACKGROUND: Ameloblastoma represents the most common epithelial odontogenic tumor. Because of the proximity of the maxillary tumors to the orbit and skull base, it should be managed as radically as possible. Maxillectomy mainly via the transfacial or transoral approach represents the most common type of surgical procedure. Drawback of these approaches is limited control of the superiomedial extent of the tumour in the paranasal area. We report the use of a combined endoscopic endonasal and transoral approach to manage maxillary plexiform ameloblastoma in a 48 year old male patient. A combined endoscopic endonasal and transoral approach enabled the radical removal of tumour with a 1.5cm margin of radiographically intact bone with good control from both intrasinusal and intraoral aspects. Adequate visualization of the extent of the lesion (e.g. orbit, infratemporal fossa, anterior cranial base) had been achieved. Non-complicated healing was achieved. This technique of partial maxillectomy led to very good aesthetic and functional results. No recurrence had been noted during review appointments.
CONCLUSION: The combination of endoscopic endonasal and transoral approach for a partial maxillectomy allows sufficient reduction of the defect thus eliminating the necessity for reconstruction and reducing the morbidity associated with it.

PMID: 29475080 [PubMed - as supplied by publisher]

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The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity.

The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity.

J Control Release. 2018 Feb 20;:

Authors: Falvo E, Malagrinò F, Arcovito A, Fazi F, Colotti G, Tremante E, Di Micco P, Braca A, Opri R, Giuffrè A, Fracasso G, Ceci P

Abstract
A genetically engineered human ferritin heavy chain (HFt)-based construct has been recently shown by our group to efficiently entrap and deliver doxorubicin to cancer cells. This construct, named HFt-MP-PAS, contained a tumor-selective sequence (MP) responsive to proteolytic cleavage by tumor proteases (MMPs), located between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). HFt-MP-PAS displayed excellent therapeutic efficacy in xenogenic pancreatic and head and neck cancer models in vivo, leading to a significant increase in overall animal survivals. Here we report a new construct obtained by the genetic insertion of two glutamate residues in the PAS sequence of HFt-MP-PAS. Such new construct, named HFt-MP-PASE, is characterized by improved performances as drug biodistribution in a xenogenic pancreatic cancer model in vivo. Moreover, HFt-MP-PASE efficiently encapsulates the anti-cancer drug mitoxantrone (MIT), and the resulting MIT-loaded nanoparticles proved to be more soluble and monodispersed than the HFt-MP-PAS counterparts. Importantly, in vitro MIT-loaded HFt-MP-PASE kills several cancer cell lines of different origin (colon, breast, sarcoma and pancreas) at least as efficiently as the free drug. Finally, our MIT loaded protein nanocages allowed in vivo an impressive incrementing of the drug accumulation in the tumor with respect to the free drug.

PMID: 29474961 [PubMed - as supplied by publisher]

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Patient reported outcomes in prospective cohort study of Electrochemotherapy.

Patient reported outcomes in prospective cohort study of Electrochemotherapy.

Int J Surg. 2018 Feb 20;:

Authors: Al-Hadithy N, Dehnel A, George A, Kisiel R, Lunt C, Stone C

Abstract
Metastatic spread of malignant tumours to skin is a well described phenomenon with incidence of approximately 0.7-9% of all metastases depending on histological type of primary cancer. Electrochemotherapy (ECT) is an efficient local tumour ablation modality that has proven clinical efficacy in the treatment of various types of tumours metastasis to skin. Aims of this study are to evaluate the activity, toxicity, and feasibility of treating patients with electrochemotherapy (ECT); their clinical outcomes and patient report outcome measures. This was a cohort study of 48 patients. In this study a good or excellent response to treatment was observed in 74% of patients on the basis of the clinical photographs. Five patients had partial responses (14%) and three patients had no response (8.5%). One patient died during the study period (2.8%). 87% of patients said they would have ECT again if clinically indicated. Spearman's' rank correlation of clinical efficacy for anatomical location was found to be positive with poorer outcomes in head and neck compared to trunk and limbs. Complications were found in 16patients, of which all were either grade 1 or 2 Clavien classification. The complications were predominantly in patients treated with ECT for tumours the head and neck area. Initial assessment of applicable patient report outcome measures for our patient cohort demonstrate that there are no validated tools exist for ECT. Further work is required here.

PMID: 29474886 [PubMed - as supplied by publisher]

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Radiographic Analysis of the Vidian Canal and Its Utility in Petrous Internal Carotid Artery Localization.

Radiographic Analysis of the Vidian Canal and Its Utility in Petrous Internal Carotid Artery Localization.

Oper Neurosurg (Hagerstown). 2018 Feb 21;:

Authors: Mason EC, Hudgins PA, Pradilla G, Oyesiku NM, Solares CA

Abstract
BACKGROUND: Endoscopic endonasal surgery of the skull base requires expert knowledge of the anatomy and a systematic approach. The vidian canal is regarded as a reliable landmark to localize the petrous internal carotid artery (pICA) near the second genu, which can be used for orientation in deep skull base approaches. There is controversy about the relationship between the vidian canal and the pICA.
OBJECTIVE: To further establish the vertical relationship between the vidian canal and the pICA to aid in surgical approaches to the skull base.
METHODS: We utilized a collection of institutional review board-approved computed tomographic (CT) angiograms (CTAs). Fifty CTAs were studied bilaterally for 100 total sides. The vidian canal was visualized radiographically to determine whether it terminates below, at, or above the level of the pICA.
RESULTS: Sixty-six of 100 vidian canals terminated inferior to the pICA (66%), which was the most common relationship observed. The average distance inferior to the pICA was 1.01 mm on the right, 1.18 mm on the left, and 1.09 mm of the total 66 sides. Less commonly, the vidian canal terminated at the level of the pICA canal in 34 sides (34%). The vidian canal was not observed to terminate superior to the pICA in any of the 50 CTAs studied.
CONCLUSION: The vidian canal terminates inferior to the pICA most commonly, but often terminates at the level of the pICA. Careful drilling clockwise inferior to superior around the vidian canal should allow for safe pICA localization in most cases.

PMID: 29474662 [PubMed - as supplied by publisher]

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The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.

The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.

PLoS One. 2018;13(2):e0193412

Authors: Tichy A, Kabacik S, O'Brien G, Pejchal J, Sinkorova Z, Kmochova A, Sirak I, Malkova A, Beltran CG, Gonzalez JR, Grepl J, Majewski M, Ainsbury E, Zarybnicka L, Vachelova J, Zavrelova A, Davidkova M, Markova Stastna M, Abend M, Pernot E, Cardis E, Badie C

Abstract
The increasing risk of acute large-scale radiological/nuclear exposures of population underlines the necessity of developing new, rapid and high throughput biodosimetric tools for estimation of received dose and initial triage. We aimed to compare the induction and persistence of different radiation exposure biomarkers in human peripheral blood in vivo. Blood samples of patients with indicated radiotherapy (RT) undergoing partial body irradiation (PBI) were obtained soon before the first treatment and then after 24 h, 48 h, and 5 weeks; i.e. after 1, 2, and 25 fractionated RT procedures. We collected circulating peripheral blood from ten patients with tumor of endometrium (1.8 Gy per fraction) and eight patients with tumor of head and neck (2.0-2.121 Gy per fraction). Incidence of dicentrics and micronuclei was monitored as well as determination of apoptosis and the transcription level of selected radiation-responsive genes. Since mitochondrial DNA (mtDNA) has been reported to be a potential indicator of radiation damage in vitro, we also assessed mtDNA content and deletions by novel multiplex quantitative PCR. Cytogenetic data confirmed linear dose-dependent increase in dicentrics (p < 0.01) and micronuclei (p < 0.001) in peripheral blood mononuclear cells after PBI. Significant up-regulations of five previously identified transcriptional biomarkers of radiation exposure (PHPT1, CCNG1, CDKN1A, GADD45, and SESN1) were also found (p < 0.01). No statistical change in mtDNA deletion levels was detected; however, our data indicate that the total mtDNA content decreased with increasing number of RT fractions. Interestingly, the number of micronuclei appears to correlate with late radiation toxicity (r2 = 0.9025) in endometrial patients suggesting the possibility of predicting the severity of RT-related toxicity by monitoring this parameter. Overall, these data represent, to our best knowledge, the first study providing a multiparametric comparison of radiation biomarkers in human blood in vivo, which have potential for improving biological dosimetry.

PMID: 29474504 [PubMed - in process]

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A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study.

A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study.

PLoS One. 2018;13(2):e0193500

Authors: Posocco B, Buzzo M, Follegot A, Giodini L, Sorio R, Marangon E, Toffoli G

Abstract
Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit-risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients' plasma, we developed a new, sensitive and specific HPLC-MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm); the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948) over the concentration ranges (1-10000 ng/mL for paclitaxel and 1-1000 ng/mL for 6α-hydroxy-paclitaxel) and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively <9.9% and within 91.1-114.8%. In addition, to further verify the assay reproducibility, we tested this method by re-analysing the incurred samples. This bioanalytical method was employed with success to a genotype-guided phase Ib study of weekly paclitaxel in ovarian cancer patients treated with a wide range of drug's dosages.

PMID: 29474420 [PubMed - in process]

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