Manganese Based Alternative to Gadolinium: Journal Watch

The use of gadolinium-based contrast agents in MR images has become one of radiology's most debated topic.  In a study published in Radiology, a manganese-based contrast agent, manganese-N-picolyl-N,N',N'-trans-1,2-cyclohexenediaminetriacetate (Mn-PyC3A) is shown  enable contrast-enhanced MR angiography with comparable contrast enhancement to gadolinium-based agents and may overcome concerns regarding gadolinium-associated toxicity and retention.   Eric M. Gale et al compared contrast material–enhanced MR angiography  in baboons by using Mn-PyC3A and Gd-DTPA. 

Reference and Further Reading 

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Reaction Time Is Negatively Associated with Corpus Callosum Area in the Early Stages of CADASIL [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Reaction time was recently recognized as a marker of subtle cognitive and behavioral alterations in the early clinical stages of CADASIL, a monogenic cerebral small-vessel disease. In unselected patients with CADASIL, brain atrophy and lacunes are the main imaging correlates of disease severity, but MR imaging correlates of reaction time in mildly affected patients are unknown. We hypothesized that reaction time is independently associated with the corpus callosum area in the early clinical stages of CADASIL.

MATERIALS AND METHODS:

Twenty-six patients with CADASIL without dementia (Mini-Mental State Examination score > 24 and no cognitive symptoms) and without disability (modified Rankin Scale score ≤ 1) were compared with 29 age- and sex-matched controls. Corpus callosum area was determined on 3D-T1 MR imaging sequences with validated methodology. Between-group comparisons were performed with t tests or ² tests when appropriate. Relationships between reaction time and corpus callosum area were tested using linear regression modeling.

RESULTS:

Reaction time was significantly related to corpus callosum area in patients (estimate = –7.4 x 10³, standard error = 3.3 x 10³, P = .03) even after adjustment for age, sex, level of education, and scores of depression and apathy (estimate = –12.2 x 10³, standard error = 3.8 x 10³, P = .005). No significant relationship was observed in controls.

CONCLUSIONS:

Corpus callosum area, a simple and robust imaging parameter, appears to be an independent correlate of reaction time at the early clinical stages of CADASIL. Further studies will determine whether corpus callosum area can be used as an outcome in future clinical trials in CADASIL or in more prevalent small-vessel diseases.

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Health-related-quality-of-life and toxicity after single fraction 19 Gy high-dose-rate prostate brachytherapy: Phase II trial

To evaluate the safety, tolerance and impact on health-related-quality-of-life (HRQoL) of the high-dose-rate brachytherapy of 19 Gy (BRT-HDR-19 Gy) single fraction in prostate cancer.

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Impact of hybrid PET/MR technology on multiparametric imaging and treatment response assessment of cervix cancer

Multimodal tissue characterization by combined MRI and PET has high clinical potential in the context of sub-target definition for dose painting and response assessment but its clinical exploration is yet limited. The aim of this study was to prove the potential and feasibility of hybrid PET/MRI to non-invasively measure tumor hypoxia, perfusion and microstructure at one stop in tumors of the uterine cervix during chemoradiotherapy.

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Late normal tissue effects in the arm and shoulder following lymphatic radiotherapy: Results from the UK START (Standardisation of Breast Radiotherapy) trials

Adjuvant lymphatic radiotherapy (LNRT) is recommended for selected axillary node positive women with early breast cancer. We investigated whether hypofractionated LNRT is safe combined with similarly-hypofractionated breast/chest wall radiotherapy (RT).

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International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma

Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome.

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Use of integra in oral reconstruction: a case series

Purpose: Small intraoral defects are usually reconstructed using skin autografts. However, the goal of this research was to describe an alternative to the classical techniques using artificial dermis (Integra®) in the reconstruction of these types of injuries. Materials and Methods: Four patients with small intraoral lesions in different locations underwent resection. The created defects were covered with a bilayer of Integra®; then, a chlorhexidine stent cure (Laboratorios Salvat, Barcelona, Spain) was applied.

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Performance of five different displays in the detection of artificial incipient and recurrent caries-like lesions

To assess whether auto-calibrating medical-grade monitors perform better than off-the-shelf monitors and tablet computers in detecting artificial incipient and recurrent caries-like lesions.

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Predictors of obturator functioning and satisfaction in turkish maxillectomy patients using an obturator prosthesis

To determine the socio-demographic, behavioral and clinical factors affecting obturator function and satisfaction using the Obturator Functioning Scale (OFS) in maxillectomy patients rehabilitated with obturator prostheses.

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Considerations in the diagnosis of oral hairy leukoplakia – an institutional experience

We report the 10-year experience with oral hairy leukoplakia (OHL) at the Division of Oral and Maxillofacial Pathology at the University of North Carolina at Chapel Hill.

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Calcified carotid artery atheromas in panoramic radiographs are associated with a first myocardial infarction: a case-control study.

The aim of this case-control study was to investigate whether subjects with a first myocardial infarction (MI) had a higher prevalence of calcified carotid artery atheromas (CCAAs) in panoramic radiographs (PRs) than age, gender, and residential area matched controls without MIs.

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Comparison between peri-implant bone level changes of implants placed during and 3 months after iliac bone grafting

The aim of this study was to compare the peri-implant bone level changes of implants placed during and 3 months after bone grafting from the iliac crest.

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Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study [PEDIATRICS]

BACKGROUND AND PURPOSE:

Childhood arteriopathies are rare but heterogenous, and difficult to diagnose and classify, especially by nonexperts. We quantified clinical and imaging characteristics associated with childhood arteriopathy subtypes to facilitate their diagnosis and classification in research and clinical settings.

MATERIALS AND METHODS:

The Vascular Effects of Infection in Pediatric Stroke (VIPS) study prospectively enrolled 355 children with arterial ischemic stroke (2010–2014). A central team of experts reviewed all data to diagnose childhood arteriopathy and classify subtypes, including arterial dissection and focal cerebral arteriopathy–inflammatory type, which includes transient cerebral arteriopathy, Moyamoya disease, and diffuse/multifocal vasculitis. Only children whose stroke etiology could be conclusively diagnosed were included in these analyses. We constructed logistic regression models to identify characteristics associated with each arteriopathy subtype.

RESULTS:

Among 127 children with definite arteriopathy, the arteriopathy subtype could not be classified in 18 (14%). Moyamoya disease (n = 34) occurred mostly in children younger than 8 years of age; focal cerebral arteriopathy–inflammatory type (n = 25), in children 8–15 years of age; and dissection (n = 26), at all ages. Vertigo at stroke presentation was common in dissection. Dissection affected the cervical arteries, while Moyamoya disease involved the supraclinoid internal carotid arteries. A banded appearance of the M1 segment of the middle cerebral artery was pathognomonic of focal cerebral arteriopathy–inflammatory type but was present in <25% of patients with focal cerebral arteriopathy–inflammatory type; a small lenticulostriate distribution infarct was a more common predictor of focal cerebral arteriopathy–inflammatory type, present in 76%. It remained difficult to distinguish focal cerebral arteriopathy–inflammatory type from intracranial dissection of the anterior circulation. We observed only secondary forms of diffuse/multifocal vasculitis, mostly due to meningitis.

CONCLUSIONS:

Childhood arteriopathy subtypes have some typical features that aid diagnosis. Better imaging methods, including vessel wall imaging, are needed for improved classification of focal cerebral arteriopathy of childhood.

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Reply: [LETTERS]

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Patient Outcomes and Cerebral Infarction after Ruptured Anterior Communicating Artery Aneurysm Treatment [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Anterior communicating artery aneurysm rupture and treatment is associated with high rates of dependency, which are more severe after clipping compared with coiling. To determine whether ischemic injury might account for these differences, we characterized cerebral infarction burden, infarction patterns, and patient outcomes after surgical or endovascular treatment of ruptured anterior communicating artery aneurysms.

MATERIALS AND METHODS:

We performed a retrospective cohort study of consecutive patients with ruptured anterior communicating artery aneurysms. Patient data and neuroimaging studies were reviewed. A propensity score for outcome measures was calculated to account for the nonrandom assignment to treatment. Primary outcome was the frequency of frontal lobe and striatum ischemic injury. Secondary outcomes were patient mortality and clinical outcome at discharge and at 3 months.

RESULTS:

Coiled patients were older (median, 55 versus 50 years; P = .03), presented with a worse clinical status (60% with Hunt and Hess Score >2 versus 34% in clipped patients; P = .02), had a higher modified Fisher grade (P = .01), and were more likely to present with intraventricular hemorrhage (78% versus 56%; P = .03). Ischemic frontal lobe infarction (OR, 2.9; 95% CI, 1.1–8.4; P = .03) and recurrent artery of Heubner infarction (OR, 20.9; 95% CI, 3.5–403.7; P < .001) were more common in clipped patients. Clipped patients were more likely to be functionally dependent at discharge (OR, 3.2; P = .05) compared with coiled patients. Mortality and clinical outcome at 3 months were similar between coiled and clipped patients.

CONCLUSIONS:

Frontal lobe and recurrent artery of Heubner infarctions are more common after surgical clipping of ruptured anterior communicating artery aneurysms, and are associated with poorer clinical outcomes at discharge.

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Cerebral Microbleeds: A Call for Standardized Advanced Neuroimaging [LETTERS]

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Emergency Department MR Imaging Scanner: Supportive Data [LETTERS]

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Radiomics Approach Fails to Outperform Null Classifier on Test Data [LETTERS]

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Real-Time Motor Cortex Mapping for the Safe Resection of Glioma: An Intraoperative Resting-State fMRI Study [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Resting-state functional MR imaging has been used for motor mapping in presurgical planning but never used intraoperatively. This study aimed to investigate the feasibility of applying intraoperative resting-state functional MR imaging for the safe resection of gliomas using real-time motor cortex mapping during an operation.

MATERIALS AND METHODS:

Using interventional MR imaging, we conducted preoperative and intraoperative resting-state intrinsic functional connectivity analyses of the motor cortex in 30 patients with brain tumors. Factors that may influence intraoperative imaging quality, including anesthesia type (general or awake anesthesia) and tumor cavity (filled with normal saline or not), were studied to investigate image quality. Additionally, direct cortical stimulation was used to validate the accuracy of intraoperative resting-state fMRI in mapping the motor cortex.

RESULTS:

Preoperative and intraoperative resting-state fMRI scans were acquired for all patients. Fourteen patients who successfully completed both sufficient intraoperative resting-state fMRI and direct cortical stimulation were used for further analysis of sensitivity and specificity. Compared with those subjected to direct cortical stimulation, the sensitivity and specificity of intraoperative resting-state fMRI in localizing the motor area were 61.7% and 93.7%, respectively. The image quality of intraoperative resting-state fMRI was better when the tumor cavity was filled with normal saline (P = .049). However, no significant difference between the anesthesia types was observed (P = .102).

CONCLUSIONS:

This study demonstrates the feasibility of using intraoperative resting-state fMRI for real-time localization of functional areas during a neurologic operation. The findings suggest that using intraoperative resting-state fMRI can avoid the risk of intraoperative seizures due to direct cortical stimulation and may provide neurosurgeons with valuable information to facilitate the safe resection of gliomas.

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Reply: [LETTERS]

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Transient Focal Neurologic Symptoms Correspond to Regional Cerebral Hypoperfusion by MRI: A Stroke Mimic in Children [PEDIATRICS]

SUMMARY:

Children who present with acute transient focal neurologic symptoms raise concern for stroke or transient ischemic attack. We present a series of 16 children who presented with transient focal neurologic symptoms that raised concern for acute stroke but who had no evidence of infarction and had unilateral, potentially reversible imaging features on vascular and perfusion-sensitive brain MR imaging. Patients were examined with routine brain MR imaging, MRA, perfusion-sensitive sequences, and DWI. Fourteen (88%) children had lateralized MRA evidence of arterial tree pruning without occlusion, all had negative DWI findings, and all showed evidence of hemispheric hypoperfusion by susceptibility-weighted imaging or arterial spin-labeling perfusion imaging at presentation. These findings normalized following resolution of symptoms in all children who had follow-up imaging (6/16, 38%). The use of MR imaging with perfusion-sensitive sequences, DWI, and MRA can help to rapidly distinguish children with conditions mimicking stroke from those with acute stroke.

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Imaging Findings of Benign Enhancing Foramen Magnum Lesions [LETTERS]

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Differences in Morphologic and Hemodynamic Characteristics for "PHASES-Based" Intracranial Aneurysm Locations [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Several recent prospective studies have found that unruptured intracranial aneurysms at various anatomic locations have different propensities for future rupture. This study aims to uncover the lack of understanding regarding rupture-prone characteristics, such as morphology and hemodynamic factors, associated with different intracranial aneurysm location.

MATERIALS AND METHODS:

We investigated the characteristics of 311 unruptured aneurysms at our center. Based on the PHASES study, we separated and compared morphologic and hemodynamic characteristics among 3 aneurysm location groups: 1) internal carotid artery; 2) middle cerebral artery; and 3) anterior communicating, posterior communicating, and posterior circulation arteries.

RESULTS:

A mixed model statistical analysis showed that size ratio, low wall shear stress area, and pressure loss coefficient were different between the intracranial aneurysm location groups. In addition, a pair-wise comparison showed that ICA aneurysms had lower size ratios, lower wall shear stress areas, and lower pressure loss coefficients compared with MCA aneurysms and compared with the group of anterior communicating, posterior communicating, and posterior circulation aneurysms. There were no statistical differences between MCA aneurysms and the group of anterior communicating, posterior communicating, and posterior circulation aneurysms for morphologic or hemodynamic characteristics.

CONCLUSIONS:

ICA aneurysms may be subjected to less rupture-prone morphologic and hemodynamic characteristics compared with other locations, which could explain the decreased rupture propensity of intracranial aneurysms at this location.

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Selective Poststent Balloon Angioplasty for Carotid Stenting [LETTERS]

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Flow Diversion with Low-Profile Braided Stents for the Treatment of Very Small or Uncoilable Intracranial Aneurysms at or Distal to the Circle of Willis [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The endovascular treatment of aneurysms located at or distal to the circle of Willis and not amenable to coiling remains a challenge. We report our experience with flow-diversion treatment using low-profile braided stents as a stent monotherapy procedure for treating distally located very small or uncoilable aneurysms.

MATERIALS AND METHODS:

We retrospectively reviewed our data bases to identify patients with aneurysms located at or distal to the circle of Willis who were treated with stent monotherapy using low-profile braided stents. The immediate and follow-up angiographic findings and clinical status of the patients were assessed.

RESULTS:

Twenty aneurysms in 19 patients were included in the study. The mean size of the aneurysms was 4.7 ± 2.4 mm. Patients were treated via telescopic implantation of 2 stents for 11 aneurysms; single-stent placement was used for the remaining aneurysms. The technical success rate was 95%. We observed a technical complication in 1 case (5.3%) and a late ischemic event in another (5.3%). The final angiographies during a mean follow-up of 14.7 months showed complete aneurysm occlusion in 73.7%. The complete occlusion rate of the aneurysms treated with telescopic stent placement was 81.8%. The modified Rankin scale scores of all patients at the last follow-up were between 0 and 2.

CONCLUSIONS:

Flow diversion with low-profile braided stents as a stent monotherapy procedure for very small or uncoilable intracranial aneurysms located at or beyond the circle of Willis is a promising, relatively safe, and durable endovascular procedure.

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Reply: [LETTERS]

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The Diagnostic Accuracy of Contrast-Enhanced CT of the Neck for the Investigation of Sialolithiasis [HEAD & NECK]

BACKGROUND AND PURPOSE:

Sialolithiasis is a common benign pathology affecting the salivary glands but it is unclear if contrast-enhanced CT, which is commonly used for investigation of head and neck pathology, can identify calculi as accurately as noncontrast CT. The aim of this study was to assess the diagnostic accuracy of contrast-enhanced CT of the neck in the diagnosis of sialolithiasis compared with noncontrast CT of the neck used as the criterion standard.

MATERIALS AND METHODS:

This was a retrospective, case-control study of 92 consecutive cases in 90 patients who underwent both noncontrast CT of the neck and contrast-enhanced CT of the neck in 2 tertiary referral centers from January 2011 to December 2015 for investigation of sialolithiasis. Axial 3-mm-section images were assessed by a fellowship-trained diagnostic neuroradiologist and diagnostic neuroradiology fellow in consensus. Blinded assessment of the contrast-enhanced CT of the neck was performed first, followed by noncontrast CT of the neck after a 2-week interval. The presence or absence of a stone and stone location and size were documented. Statistical analysis was undertaken to assess the agreement between CT protocols and calculate the sensitivity and specificity of contrast-enhanced CT of the neck.

RESULTS:

Fifty calculi were identified on noncontrast CT of the neck in 31 cases; and 48 calculi, in 31 cases on contrast-enhanced CT of the neck. No calculi were identified in the remaining 61 cases. The sensitivity and specificity of contrast-enhanced CT of the neck in the detection of sialolithiasis was 96% (95% CI, 86.3%–99.5%) and 100% (95% CI, 94.1%–100%), respectively. The positive predictive value of contrast-enhanced CT of the neck was 100% (95% CI, 92.6%–100%), and the negative predictive value was 96.8% (95% CI, 89%–99.6%). The accuracy of contrast-enhanced CT of the neck in diagnosing the presence or absence of salivary calculi was 98%.

CONCLUSIONS:

Contrast-enhanced CT of the neck is accurate in the detection of sialolithiasis, with no difference in diagnostic accuracy compared with noncontrast CT of the neck.

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Open Globe Injury: Ultrasound First! [LETTERS]

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Does the Addition of a "Black Bone" Sequence to a Fast Multisequence Trauma MR Protocol Allow MRI to Replace CT after Traumatic Brain Injury in Children? [PEDIATRICS]

BACKGROUND AND PURPOSE:

Head CT is the current neuroimaging tool of choice in acute evaluation of pediatric head trauma. The potential cancer risks of CT-related ionizing radiation should limit its use in children. We evaluated the role of MR imaging, including a "black bone" sequence, compared with CT in detecting skull fractures and intracranial hemorrhages in children with acute head trauma.

MATERIALS AND METHODS:

We performed a retrospective evaluation of 2D head CT and brain MR imaging studies including the black bone sequence of children with head trauma. Two experienced pediatric neuroradiologists in consensus created the standard of reference. Another pediatric neuroradiologist blinded to the diagnosis evaluated brain MR images and head CT images in 2 separate sessions. The presence of skull fractures and intracranial posttraumatic hemorrhages was evaluated. We calculated the sensitivity and specificity of CT and MR imaging with the black bone sequence in the diagnosis of skull fractures and intracranial hemorrhages.

RESULTS:

Twenty-eight children (24 boys; mean age, 4.89 years; range, 0–15.5 years) with head trauma were included. MR imaging with the black bone sequence revealed lower sensitivity (66.7% versus 100%) and specificity (87.5% versus 100%) in identifying skull fractures. Four of 6 incorrectly interpreted black bone MR imaging studies showed cranial sutures being misinterpreted as skull fractures and vice versa.

CONCLUSIONS:

Our preliminary results show that brain MR imaging complemented by a black bone sequence is a promising nonionizing alternative to head CT for the assessment of skull fractures in children. However, accuracy in the detection of linear fractures in young children and fractures of aerated bone remains limited.

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REPLY: [LETTERS]

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T1-Weighted Dynamic Contrast-Enhanced MR Perfusion Imaging Characterizes Tumor Response to Radiation Therapy in Chordoma [SPINE]

BACKGROUND AND PURPOSE:

Chordomas notoriously demonstrate a paucity of changes following radiation therapy on conventional MR imaging. We hypothesized that dynamic contrast-enhanced MR perfusion imaging parameters of chordomas would change significantly following radiation therapy.

MATERIALS AND METHODS:

Eleven patients with pathology-proved chordoma who completed dynamic contrast-enhanced MR perfusion imaging pre- and postradiation therapy were enrolled. Quantitative tumor measurements were obtained by 2 attending neuroradiologists. ROIs were used to calculate vascular permeability and plasma volume and generate dynamic contrast-enhancement curves. Quantitative analysis was performed to determine mean and maximum plasma volume and vascular permeability values, while semiquantitative analysis on averaged concentration curves was used to determine the area under the curve. A Mann-Whitney U test at a significance level of P < .05 was used to assess differences of the above parameters between pre- and postradiation therapy.

RESULTS:

Plasma volume mean (pretreatment mean = 0.82; posttreatment mean = 0.42), plasma volume maximum (pretreatment mean = 3.56; posttreatment mean = 2.27), and vascular permeability mean (pretreatment mean = 0.046; posttreatment mean = 0.028) in the ROIs significantly decreased after radiation therapy (P < .05); this change thereby demonstrated the potential for assessing tumor response. Area under the curve values also demonstrated significant differences (P < .05).

CONCLUSIONS:

Plasma volume and vascular permeability decreased after radiation therapy, suggesting that these dynamic contrast-enhanced MR perfusion parameters may be useful for monitoring chordoma growth and response to radiation therapy. Additionally, the characteristic dynamic MR signal intensity–time curve of chordoma may provide a radiographic means of distinguishing chordoma from other spinal lesions.

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[other]

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Evaluation of sequential SPECT and CT for targeted radionuclide therapy dosimetry

Abstract

Purpose

In targeted radionuclide therapy (TRT), a prior knowledge of the absorbed dose biodistribution is essential for pre-therapy treatment planning. Previously, we showed that non-rigid organ-by-organ registration in sequential quantitative SPECT images improved dose estimation. This study aims to investigate if sequential CT can further improve TRT dosimetric accuracy.

Methods

We simulated SPECT/CT acquisitions at 1, 12, 24, 72 and 144 h In-111 Zevalin post-injection using an analytical MEGP projector, modeling attenuation, scatter and collimator-detector response. We later recruited a patient injected with 222 MBq In-111 DTPAOC imaged at 3 SPECT/CT sessions for clinical evaluations. Four registration schemes were evaluated: whole-body-based registration performed on sequential (1) SPECT (WB-SPECT) or (2) CT (WB-CT) images; organ-based registration applied on organs individually segmented from sequential (3) SPECT (O-SPECT) or (4) CT (O-CT) images. Voxel-by-voxel integration was performed followed by Y-90 voxel-S-kernel convolution. Organ-absorbed doses, iso-dose curves, dose–volume histograms (DVHs) were generated for targeted organs for analysis.

Results:

In simulation study, organ-absorbed dose errors were (− 8.66 ± 2.83)%, (− 2.51 ± 3.69)%, (− 9.23 ± 3.28)%, (− 7.17 ± 2.53)% for liver, (− 14.81 ± 4.91)%, (− 3.60 ± 4.37)%, (− 18.13 ± 4.44)%, (− 11.34 ± 4.22)% for spleen, for O-SPECT, O-CT, WB-SPECT and WB-CT registrations, respectively. For all organs, O-CT showed superior results. Results of iso-dose contour, DVHs were in accordance with the organ-absorbed doses. In clinical studies, the results were also consistent which showed O-CT method deviated the most from the result with no registration.

Conclusions:

We conclude that if both sequential SPECT/CT scans are available, CT organ-based registration method can more effectively improve the 3D dose estimation. Sequential low-dose CT scans might be considered to be included in the standard TRT protocol.

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Intrakranielle zystische Läsionen

Zusammenfassung

Klinisches Problem

Bei der Bildgebung des Neurokraniums sind intrazerebrale Zysten häufig und haben nicht immer einen Krankheitswert. Das Spektrum der intrazerebralen Zysten ist jedoch sehr groß und beinhaltet neben Inzidentalbefunden auch Entwicklungsstörungen, Missbildungstumoren, primäre und sekundäre Neoplasien sowie infektiologische Ursachen, wie z. B. zerebrale Abszedierungen, die Zystizerkose oder Residuen nach konnataler Zytomegalievirusinfektion. Intrazerebrale zystische Defekte lassen sich auch bei entzündlichen Erkrankungen des Zentralnervensystems wie der Multiplen Sklerose, aber auch bei Mitochondropathien, bei Leukodystrophien, nach Elektrolytentgleisungen als Residuen einer Myelinolyse oder nach Hirninfarkten z. B. bei alten lakunären Infarkten beobachten. Daneben können auch andere Defektareale zystisch imponieren, wie z. B. bei zystischen Enzephalomalazien nach einem Schädel-Hirn-Trauma.

Radiologische Standardverfahren

Neben den radiologischen Befunden der Zysten in der Magnetresonanztomographie (MRT) bzw. in der Computertomographie (CT) helfen die Lokalisation, das Patientenalter, die Anamnese und die Labordiagnostik bei der Differenzialdiagnose.

Methodische Innovation

Neben der morphologischen Beurteilung können Advanced-MRT-Techniken wie die Diffusionsbildgebung beim Epidermoid oder der Einsatz der MR-Spektroskopie wertvolle Zusatzinformationen für die Differenzialdiagnose liefern.

Leistungsfähigkeit/Bewertung

Intrakranielle Zysten können unterteilt werden in intra- und periventrikuläre Zysten, intraaxiale Zysten sowie Zysten in den externen Liquorräumen. Assoziierte Tumornodularitäten und das Kontrastmittelverhalten der Zystenwand und/oder assoziierter Weichteilanteile sowie die Reaktion des angrenzenden Parenchyms helfen bei der Diagnosefindung und Bewertung.

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miR-15a-5p suppresses endometrial cancer cell growth via Wnt/β-catenin signaling pathway by inhibiting WNT3A

OBJECTIVE: Endometrial cancer is one of the three most common types of gynecologic cancer. The global incidence has increased in recent years. microRNAs (miRNAs) regulate numerous biological processes by binding to the 3'UTR of target mRNA to down-regulate protein synthesis.

PATIENTS AND METHODS: Endometrial cancer patients received surgeries in our hospital were enrolled. MiR-15a-5p mimic or miR-15a-5p inhibitor was transfected into HEC-1-A cells by lentivirus. Colony formation assay was applied for detecting cell proliferation. Real-time PCR was performed to test miRNA and mRNA expression. Western blot was used to detect protein level. ChIP was adopted to test transcription activation. TOP/FOP was tested to determine Wnt signaling pathway activity. A dual-luciferase reporter assay was used to confirm miRNA target.

RESULTS: miR-15a-5p was decreased in endometrial cancer cells and tissues. miR-15a-5p overexpression restrained HEC-1-A cell proliferation and stemness. miR-15a-5p mimic transfection reduced mRNA and protein levels of the proteins which are related to cell proliferation and Wnt signaling pathway. MiR-15a-5p targeted a putative binding site in the 3'-UTR of Wnt3a gene, thus regulating Wnt signaling pathway. miR-15a-5p overexpression decreased Wnt3a protein expression. Wnt3a presented significant negative correlation with the miR-15a-5p level in endometrial cancer patients.

CONCLUSIONS: miR-15a-5p is a regulator of endometrial cancer cell proliferation by directly targeting Wnt3a to block Wnt signaling pathway.

L'articolo miR-15a-5p suppresses endometrial cancer cell growth via Wnt/β-catenin signaling pathway by inhibiting WNT3A sembra essere il primo su European Review.

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Application of dynamic CT to identify lung cancer, pulmonary tuberculosis, and pulmonary inflammatory pseudotumor

OBJECTIVE: To determine the value of dynamic enhanced computed tomography (CT) scanning in diagnosing lung cancer, pulmonary tuberculosis, and pulmonary inflammatory pseudotumor.

PATIENTS AND METHODS: We recruited 30 patients with pulmonary tuberculoma, 38 with lung cancer, and 16 with pulmonary inflammatory pseudotumor. All patients received CT scanning, dynamic enhanced CT scanning for 20, 30, 45, 60, 75, 90, and 120 s, and scanning for 3, 5, 8, 12, and 15 min. Then, we compared several parameters to determine which ones help with each diagnosis.

RESULTS: The time-density curve for patients with pulmonary tuberculoma was low and flat, and significantly different from lung cancer and inflammatory pseudotumor. The 15 min clearance value and the clearance value for lung cancer and inflammatory pseudotumor were significantly different. The type II time-density curve was common in lung cancer group, whereas the type III time-density curve was common in inflammatory pseudotumor.

CONCLUSIONS: Dynamic enhanced CT scanning demonstrated the ability to differentiate lung cancer, pulmonary tuberculosis, and pulmonary inflammatory pseudotumor, indicating its diagnostic value.

L'articolo Application of dynamic CT to identify lung cancer, pulmonary tuberculosis, and pulmonary inflammatory pseudotumor sembra essere il primo su European Review.

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Cardiac magnetic resonance in systemic sclerosis patients with cardiac symptoms

OBJECTIVE: Systemic sclerosis (SSc) is characterized by widespread vascular lesions and skin and internal organs fibrosis, including the heart; all cardiac layers, endocardium, myocardium, and pericardium, may be involved. We report the relevance of cardiac MRI findings in scleroderma patients with cardiac symptoms.

PATIENTS AND METHODS: 50 patients, all fulfilling the ACR SSc criteria (19 with limited and 31 with diffused skin involvement) were evaluated using a 1.5T MR scanner. Images were acquired before and after contrast medium administration; the exams were considered positive with one or more of these findings: enlarged volumes, reduced EF, regional kinetic anomalies, edema, DE or pericardial effusion.

RESULTS: 40 patients (80%) had one or more cardiac abnormalities: 5 patients had myocardial edema; 2 an increased interventricular septum thickness; 22 dilated ventricles or reduced EF; 12 an abnormal regional ventricular motion (2 of these with akinetic segments); 17 a delayed enhancement with different patterns, all without coronary distribution; 22 a pericardial effusion

CONCLUSIONS: Pathologic findings were documented in 80% of the cases confirming a high occurrence of abnormal MR data. Myocardial involvement in systemic sclerosis can be assumed by the presence of multiple pathologic MRI findings. CMR seems to be a valuable tool to identify and assess the presence of cardiac involvement.

L'articolo Cardiac magnetic resonance in systemic sclerosis patients with cardiac symptoms sembra essere il primo su European Review.

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An updated review on tritium in the environment

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): Frédérique Eyrolle, Loïc Ducros, Séverine Le Dizès, Karine Beaugelin-Seiller, Sabine Charmasson, Patrick Boyer, Catherine Cossonnet
Various studies indicated more or less recently that organically bound tritium (OBT) formed from gaseous or liquid tritium releases into the environment potentially accumulates in organisms contradicting hypotheses associated to methods used to assess the biological impact of tritium on humans (ASN, 2010). Increasing research works were then performed during the last decade in order to gain knowledge on this radionuclide expected to be increasingly released by nuclear installations in the near future within the environment. This review focusses on publications of the last decade. New unpublished observations revealing the presence of technogenic tritium in a sedimentary archive collected in the upper reaches of the Rhône river and findings from the Northwestern Mediterranean revealing in all likelihood the impact of terrigenous tritium inputs on OBT levels recorded in living organisms are also presented. Identifying and understanding the physicochemical forms of tritium and the processes leading to its persistence in environmental compartments would explain most observations regarding OBT concentrations in organisms and definitively excludes that tritium would "bio accumulate" within living organisms.



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Nitrogen species coupled with transpiration enhance Fe plaque assisted aquatic uranium removal via rhizofiltration of Phragmites australis Trin ex Steud

Publication date: Available online 14 November 2017
Source:Journal of Environmental Radioactivity
Author(s): Weiqing Wang, E. Gert Dudel
The influences of N species and transpiration on the Fe plaque (IP) formation and related aquatic U rhizofiltration had not revealed yet, especially when these factors were co-existed. It was evaluated in a mesocosm experiment in the condition of respective ammonium (NH4⁺)/nitrate (NO3⁻) cultivation of Phragmites australis Trin ex Steud. coupled with different transpiration rates (TRs). The results suggested that the enhanced transpiration of P. australis improved the aquatic U rhizofiltration in both NO3⁻ and NH4⁺ rich milieus. However, the NO3⁻ dependent oxidizing milieu restricted aquatic U uptake by the root of P. australis (up to 47.6 ± 1.8 mg kg⁻¹ under high TR) via IP assisted rhizofiltration. The high aquatic U availability and limited IP formation in NO3⁻ rich milieu benefited the U retention within root tissue. On the contrary, the aquatic U rhizofiltration (up to 62.1 ± 1.0 mg kg⁻¹ under high TR) was enhanced under NH4⁺ dependent reductive milieu. It was mainly contributed by U retention within IP. The area related U accumulation in different N species cultured roots was enhanced but did not significantly different under higher TR condition. The result suggested that the supplied NH4⁺ coupled with enhanced transpiration was supposed to be more optimized option for IP assisted aquatic U rhizofiltration via P. australis.



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Evaluation of the solitary pulmonary nodule: size matters, but do not ignore the power of morphology

Abstract

Subsequent to the widespread use of multidetector computed tomography and growing interest in lung cancer screening, small pulmonary nodules are more frequently detected. The differential diagnosis for a solitary pulmonary nodule is extremely broad and includes both benign and malignant causes. Recognition of early lung cancers is vital, since stage at diagnosis is crucial for prognosis. Estimation of the probability of malignancy is a challenging task, but crucial for follow-up and further work-up. In addition to the clinical setting and metabolic assessment, morphological assessment on thin-section computed tomography is essential. Size and growth are key factors in assessment of the malignant potential of a nodule. The likelihood of malignancy positively correlates with nodule diameter: as the diameter increases, so does the likelihood of malignancy. Although there is a considerable overlap in the features of benign and malignant nodules, the importance of morphology however should not be underestimated. Features that are associated with benignity include a perifissural location and triangular morphology, internal fat and benign calcifications. Malignancy is suspected in nodules presenting with spiculation, lobulation, pleural indentation, vascular convergence sign, associated cystic airspace, bubble-like lucencies, irregular air bronchogram, and subsolid morphology. Nodules often show different features and combination of findings is certainly more powerful.

Teaching points

• Size of a pulmonary nodule is important, but morphological assessment should not be underestimated.

• Lung nodules should be evaluated on thin section CT, in both lung and mediastinal window setting.

• Features associated with benignity include a triangular morphology, internal fat and calcifications.

• Spiculation, pleural retraction and notch sign are highly suggestive of a malignant nature.

• Complex features (e.g. bubble-like lucencies) are highly indicative of a malignant nature.

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Role of magnetic resonance imaging in the management of perianal Crohn’s disease

Abstract

Perianal fistulas are a major problem in many patients with Crohn's disease. These are usually complex fistulas that adversely affect patients' quality of life, and their clinical management is difficult. Medical treatment sometimes achieves cessation of discharge and closure of the external opening; however, it is difficult to assess the status of the rest of the fistula tract. Magnetic resonance imaging is the method of choice with which to evaluate the condition of perianal fistulas and allows for assessment of the status of inaccessible areas. Magnetic resonance imaging also allows the clinician to evaluate other perianal manifestations of Crohn's disease that differ from the fistulas. This imaging technique is therefore a fundamental means of patient monitoring. When used in conjunction with assessment of the patient's morphological findings, it provides information that allows for both quantification of disease severity and evaluation of the response to treatment. New types of magnetic resonance sequences are emerging, such as diffusion, perfusion, and magnetisation transfer. These sequences may serve as biomarkers because they provide information reflecting the changes taking place at the molecular level. This will help to shape a new scenario in the early assessment of the response to treatments such as anti-tumour necrosis factor drugs.

Teaching points

• MRI is the method of choice with which to evaluate perianal fistulas.

• In perianal Crohn's disease, MRI is a fundamental means of patient monitoring.

• The usefulness of the Van Assche score for patient monitoring remains unclear.

• New MRI sequences' diffusion, perfusion, and magnetisation transfer may serve as biomarkers.

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Radiofrequency Ablation versus Hepatic Resection for Small Hepatocellular Carcinoma: Systematic Review of Randomized Controlled Trials with Meta-Analysis and Trial Sequential Analysis.

Radiofrequency Ablation versus Hepatic Resection for Small Hepatocellular Carcinoma: Systematic Review of Randomized Controlled Trials with Meta-Analysis and Trial Sequential Analysis.

Radiology. 2017 Nov 13;:162756

Authors: Xu XL, Liu XD, Liang M, Luo BM

Abstract
Purpose To compare the benefits and harms of radiofrequency ablation (RFA) and hepatic resection (HR) and to test the consistency of currently available evidence. Materials and Methods PubMed, Embase, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared the effects of HR and RFA for Barcelona Clinic Liver Cancer very early or early stage hepatocellular carcinoma (HCC). The primary outcome was overall survival, and secondary outcomes were recurrence rate, complication rate, and hospitalization duration. A random- or fixed-effects model according to the level of heterogeneity was applied. The meta-analysis was performed by using software, and trial sequential analysis (TSA) was performed. Results Five trials examining 742 patients were included in this study (sizes of trials: 161, 230, 168, 120, and 63 patients). The meta-analysis showed that RFA and HR had similar overall survival at 1 year (relative risk [RR], 1.39; 95% confidence interval [CI]: 0.36, 5.33; P = .63) and 3 years (RR, 1.40; 95% CI: 0.75, 2.62; P = .29), whereas RFA resulted in decreased overall survival compared with HR at 5 years (RR: 1.91; 95% CI: 1.32, 2.79; P = .001). The TSA showed that more trials were needed to control random errors. The incidence of overall recurrence was markedly higher and the hospitalization duration was significantly shorter in the RFA group than in the HR group, which was confirmed by TSA. Complications may have been less frequent in the RFA group, but TSA showed that additional trials were necessary to confirm this conclusion. Conclusion The indication for RFA as a primary treatment for patients who are eligible for HR with early stage HCC is unclear, and additional well-designed RCTs are needed. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29135366 [PubMed - as supplied by publisher]

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Deep Learning to Classify Radiology Free-Text Reports.

Deep Learning to Classify Radiology Free-Text Reports.

Radiology. 2017 Nov 13;:171115

Authors: Chen MC, Ball RL, Yang L, Moradzadeh N, Chapman BE, Larson DB, Langlotz CP, Amrhein TJ, Lungren MP

Abstract
Purpose To evaluate the performance of a deep learning convolutional neural network (CNN) model compared with a traditional natural language processing (NLP) model in extracting pulmonary embolism (PE) findings from thoracic computed tomography (CT) reports from two institutions. Materials and Methods Contrast material-enhanced CT examinations of the chest performed between January 1, 1998, and January 1, 2016, were selected. Annotations by two human radiologists were made for three categories: the presence, chronicity, and location of PE. Classification of performance of a CNN model with an unsupervised learning algorithm for obtaining vector representations of words was compared with the open-source application PeFinder. Sensitivity, specificity, accuracy, and F1 scores for both the CNN model and PeFinder in the internal and external validation sets were determined. Results The CNN model demonstrated an accuracy of 99% and an area under the curve value of 0.97. For internal validation report data, the CNN model had a statistically significant larger F1 score (0.938) than did PeFinder (0.867) when classifying findings as either PE positive or PE negative, but no significant difference in sensitivity, specificity, or accuracy was found. For external validation report data, no statistical difference between the performance of the CNN model and PeFinder was found. Conclusion A deep learning CNN model can classify radiology free-text reports with accuracy equivalent to or beyond that of an existing traditional NLP model. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29135365 [PubMed - as supplied by publisher]

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Restrictive Cardiomyopathies: The Importance of Noninvasive Cardiac Imaging Modalities in Diagnosis and Treatment—A Systematic Review

Restrictive cardiomyopathy (RCM) is the least common among cardiomyopathies. It can be idiopathic, familial, or secondary to systematic disorders. Marked increase in left and/or right ventricular filling pressures causes symptoms and signs of congestive heart failure. Electrocardiographic findings are nonspecific and include atrioventricular conduction and QRS complex abnormalities and supraventricular and ventricular arrhythmias. Echocardiography and cardiac magnetic resonance (CMR) play a major role in diagnosis. Echocardiography reveals normal or hypertrophied ventricles, preserved systolic function, marked biatrial enlargement, and impaired diastolic function, often with restrictive filling pattern. CMR offering a higher spatial resolution than echocardiography can provide detailed information about anatomic structures, perfusion, ventricular function, and tissue characterization. CMR with late gadolinium enhancement (LGE) and novel approaches (myocardial mapping) can direct the diagnosis to specific subtypes of RCM, depending on the pattern of scar formation. When noninvasive studies have failed, endomyocardial biopsy is required. Differentiation between RCM and constrictive pericarditis (CP), nowadays by echocardiography, is important since both present as heart failure with normal-sized ventricles and preserved ejection fraction but CP can be treated by means of anti-inflammatory and surgical treatment, while the treatment options of RCM are dictated by the underlying condition. Prognosis is generally poor despite optimal medical treatment.

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Clinical outcomes and prognostic factors of radioiodine ablation therapy for lymph node metastases from papillary thyroid carcinoma.

Clinical outcomes and prognostic factors of radioiodine ablation therapy for lymph node metastases from papillary thyroid carcinoma.

Nucl Med Commun. 2017 Nov 10;:

Authors: Wu X, Gu H, Gao Y, Li B, Fan R

Abstract
OBJECTIVE: A total of 118 patients with papillary thyroid carcinoma treated with radioactive iodine for lymph node metastases were analyzed retrospectively between August 2008 and June 2014. We describe the clinical course of these patients and focus on factors associated with lymph node metastases response to iodine-131 (I) treatment.
PATIENTS AND METHODS: A total of 118 postoperative papillary thyroid carcinoma patients who underwent I treatment with lymph nodes as the only site of metastasis on whole-body scan (I Rx-WBS) and single-photon emission computed tomography-computed tomography (SPECT-CT) were enrolled. Clinical and laboratory evaluations including I Rx-WBS, serum thyroglobulin level, and radiographic findings were carried out during follow-up.
RESULTS: At the end of follow-up, the rates of complete remission and partial response were 28.0% (33/118) and 52.5% (62/118), respectively. An overall effective rate of 80.5% (95/118) was obtained after three times radioiodine therapy and administration of 3.7-16.7 GBq I.
CONCLUSION: Our data indicate that I therapy is highly effective in the treatment of lymph node metastases from papillary thyroid carcinoma; patients with a small size of metastatic lymph node, younger patients, those with lower thyroglobulin levels, and patients with lymph node metastases detectable on the first postablative I Rx-WBS and single-photon emission computed tomography-computed tomography showed a good response to radioiodine ablation therapy.

PMID: 29135721 [PubMed - as supplied by publisher]

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RT @ecancer_espanol : Solo 4 días para nuestro https://t.co/b9UK7cuSb6 los esperamos! https://t.co/PvpvjTHgTq

RT @ecancer_espanol : Solo 4 días para nuestro https://t.co/b9UK7cuSb6 los esperamos! https://t.co/PvpvjTHgTq

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RT @ecancer_espanol : Programa especial para la comunidad: Movilizando a la sociedad para la prevención y control del cáncer de mama https:/…

RT @ecancer_espanol : Programa especial para la comunidad: Movilizando a la sociedad para la prevención y control del cáncer de mama https:/…

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Differentielle therapeutische und pädagogische Entscheidungen in der Behandlung von Kindern und Jugendlichen

Aus dem zunehmenden Wissen um die Verschiedenheit ihrer Wirkungen resultiert die Forderung nach empirisch begründeten Auswahlentscheidungen zwischen verschiedenen Psychotherapiemethoden im klinischen Einzelfall. Die den jeweiligen Psychotherapieschulen innewohnenden Verstehensregeln erschweren aber die am Kriterium der Wirkung orientierte praktische Handhabung des differentiellen Auswählens. Eine Untersuchung wird beschrieben, die klären helfen will, ob und in welcher Weise differentielle Entscheidungen in der klinischen Praxis getroffen werden. Dazu wurden insgesamt 3130 Therapieentscheidungen klinisch tätiger Ärzte und Psychologen einer kinderpsychiatrischen Universitätsklinik retrospektiv untersucht. Die häufigsten Behandlungsentscheidungen waren (1) pädagogische Einzelfallhilfemaßnahmen, (2) Verhaltenstherapie, (3) klientenzentrierte Spieltherapie und (4) analytische Psychotherapie. Im Ergebnis ließen sich für diese vier Behandlungskonzepte durchaus unterschiedliche Indikationsprofile aufzeigen. Die Gründe für diese differentielle Entscheidungspraxis liegen vermutlich weniger in einem gelungenen Transfer zwischen Forschung und Praxis als vielmehr in erfahrungsbedingten Selektionsprozessen. Es werden Schlussfolgerungen für die Ausbildungspraxis gezogen.

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[Treatment of phenylketonuria: psychological results of a 5-year follow-up study (author's transl)]

In addition to earlier reports findings of a psychological five-year-follow-up of PKU-children are presented. Intelligence and motor development of these children depend significantly on age at onset of therapy and quality of dietary control. After dietary treatment over several years older PKU-children with late onset of therapy display no structural change as far as cognitive and motor development are concerned. Furthermore, a psychodiagnostic approach is presented to predict quality of dietary control. Although this approach did not yet yeald positive results because of insufficient sample-size it should be applied to further studies in the future.

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Hyperphenylalaninemia: Effect of late treatment in to siblings

The effect of late treatment with a low phenylalanine diet on cognitive, motor and social development in two siblings with persistent hyperphenylalaninemia is described. The disease state is characterized by the results of laboratory investigations including serum phenylalanine and serum tyrosine levels and aromatic acid excretion following L-phenylalanine load in the patients and their parents. A suggestion is made to treat patients with persistent hyperphenylalaninemia if repeated serum phenylalanine levels on unrestricted diet exceed 12 mg/100 ml. Es wird der Effekt einer spät einsetzenden phenylalaninarmen Diät bei zwei Brüdern mit persistierender Hyperphenylalaninämie beschrieben. Der Krankheitszustand wird charakterisiert durch die Ergebnisse einer oralen LPhenylalaninbelastung auf Serumspiegel von Phenylalanin und Tyrosin und auf die Ausscheidung aromatischer Säuren im Urin bei den Patienten sowie deren Eltern. Es wird vorgeschlagen, Patienten mit persistierender Hyperphenylalaninämie dann zu behandeln, wenn wiederholte Messungen von Phenylalanin im Serum unter normaler Kost die Grenze von 12 mg/100 ml überschreiten.

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Combining stable carbon isotope analysis and petroleum-fingerprinting to evaluate petroleum contamination in the Yanchang oilfield located on loess plateau in China

Abstract

This study evaluated petroleum contamination in the Yanchang (Shaanxi Yanchang Petroleum (Group) Co., Ltd.) oilfield, located in the loess plateau region of northern Shaanxi, China. Surface soil and sediment samples were collected from the wasteland, farmland, and riverbed in this area to assess the following parameters: total petroleum hydrocarbon (TPH), n-alkanes, polycyclic aromatic hydrocarbons (PAHs), and carbon isotope ratios (δ¹³C). The results showed that TPH and PAH levels in the study area were 907–3447 mg/kg and 103.59–563.50 μg/kg, respectively, significantly higher than the control samples (TPH 224 mg/kg, PAHs below method quantification limit, MQL). Tests using δ¹³C to detect modified TPH (2238.66 to 6639.42 mg/kg) in the wastelands adjacent to the oil wells revealed more significant contamination than tests using extraction gravimetric analysis. In addition, “chemical fingerprint” indicators, such as low to high molecular weight (LMW/HMW) hydrocarbons, carbon preference index (CPI), and pristine/phytane (Pr/Ph), further confirmed the presence of heavy petroleum contamination and weathering. This has resulted in a nutrient imbalance and unsuitable pH and moisture conditions for microbial metabolic activities. This study evaluates petroleum contamination, which can inform contamination remediation on a case by case basis.

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Cornell study reveals why testicular cancer is so responsive to chemo

Cornell researchers have taken a major step toward answering a key question in cancer research: Why is testicular cancer so responsive to chemotherapy, even after it metastasises? The key to such success appears to lie in the cancer's stem cells, which...

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Development of new protein may lead to novel treatment options for cancer

Researchers have engineered an artificial protein that may block malignant properties of cancer cells as well as correct certain birth defects. The findings, which appear in Proceedings of the National Academy of Sciences, may lead to identifying new...

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IJMS, Vol. 18, Pages 2420: Molecular-Targeted Therapies for Epidermal Growth Factor Receptor and Its Resistance Mechanisms

IJMS, Vol. 18, Pages 2420: Molecular-Targeted Therapies for Epidermal Growth Factor Receptor and Its Resistance Mechanisms

International Journal of Molecular Sciences doi: 10.3390/ijms18112420

Authors: Toshimitsu Yamaoka Motoi Ohba Tohru Ohmori

Cancer therapies targeting epidermal growth factor receptor (EGFR), such as small-molecule kinase inhibitors and monoclonal antibodies, have been developed as standard therapies for several cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, and squamous cell carcinoma of the head and neck. Although these therapies can significantly prolong progression-free survival, curative effects are not often achieved because of intrinsic and/or acquired resistance. The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations, activation of alternative pathways, phenotypic transformation, and resistance to apoptotic cell death. Analysis of the processes that modulate EGFR signal transduction by EGFR-targeted inhibitors, such as tyrosine kinase inhibitors and monoclonal antibodies, has revealed new therapeutic opportunities and has elucidated novel mechanisms contributing to the discovery of more effective anticancer treatments. In this review, we discuss the roles of EGFR in cancer development, therapeutic strategies for targeting EGFR, and resistance mechanisms to EGFR-targeted therapies, with a focus on cancer therapies for individual patients.

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Current Therapeutic Options for Heart Failure in Elderly Patients

Heart failure (HF) is a major and growing public health problem with high morbidity and mortality (Ponikowski et al., 2016). It affects 1-2% of the general population in developed countries, and the average age at diagnosis is 76 years. Because of a better management of acute phase and comorbidities, HF incidence is increasing in elderly patients, with a prevalence rising to 10% among people aged 65 years or older (Mozaffarian et al., 2014). Therefore, a substantial number of elderly patients need to be treated. However, because of clinical trial exclusion criteria or coexisting comorbidities, currently recommended therapies are widely based on younger population with a much lower mean age. In this review, we will focus on available pharmacological, electrical, and mechanical therapies, underlining pros, cons, and practical considerations of their use in this specific patient population.

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Simulation of the Impacts of Urbanization on Winter Meteorological Fields over the Pearl River Delta Region

The influences of urbanization on weather in Guangdong Province, China, were studied using the Weather Research and Forecasting model from 31 December 2009 through 3 January 2010. Model outputs were compared with extensive monitoring of meteorological data to examine the simulation ability. Model results between tests (with and without land-use change) show that the urbanization had major effects on meteorological fields across nearly the entire Pearl River Delta region and particularly in urban areas. Studied fields (wind speed, temperature, precipitation, and sensible and latent heat fluxes) were affected by the urbanization of the PRD region. The major influences occurred in urban areas, where wind speeds decreased greatly, while the daytime surface upward sensible heat flux clearly increased. Unlike the sensible heat flux, the latent heat flux had a nonmonotonic increase or decrease. As a consequence of the two heat fluxes, 2-m temperature varied with location and time. Change of precipitation was complex. The main rain band became more concentrated, while precipitation decreased upwind of the urban area and increased downwind.

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Sciatic Nerve Palsy following Total Hip Replacement: Are Patients Personal Characteristics More Important than Limb Lengthening? A Systematic Review

Sciatic nerve palsies are rare but potentially devastating complications, accounting for more than 90% of neurologic injuries following total hip replacement. A systematic literature screening was carried out searching papers evaluating an exclusive population of postarthroplasty sciatic nerve palsies to ascertain (1) the influence of limb lengthening itself on sciatic nerve palsy, (2) the most important risk factors, (3) the long-term prognosis, and (4) the outcomes of different treatments. Fourteen manuscripts were finally included. The wide prevalence of retrospective case series decreased the global methodological quality of the retrieved papers. A hazardous lengthening threshold cannot be surely identified. Developmental dysplasia of the hip and previous hip surgeries are the most frequently recognized risk factors. Rate of full nerve function restoration approximates two-thirds of the cases, independently of the extent of initial neural damage. Poor evidences are available about the best treatment strategy. Well-structured multicentric prospective comparative studies are needed to substantiate or contrast the finding of this review. Anyway, since the onset of palsies is probably due to a combination of individual factors, risk of nerve damage and potential for nerve recovery should be evaluated on an individual basis.

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Translational Hemorrhagic Stroke: Physiology, Pharmaceutical Drugs, and Management

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Q Fever Presented as a Large Retroperitoneal Pseudotumoral Mass

Background. Q fever is an infection caused by Coxiella burnetii, an intracellular organism. Acute infection is most often a benign and asymptomatic process; however, some individuals may go on to develop subacute and persistent localized symptomatic Q fever. As such, the clinical and histopathologic findings of Q fever are widely variable and may be missed if clinical suspicion is not high. Case Presentation. Herein we report the first case of C. burnetii infection presenting as an isolated retroperitoneal mass. A 61-year-old male underwent axillary-bifemoral bypass surgery. His postoperative course was complicated by the discovery of a large retroperitoneal mass. Conclusion. Clinical and histopathologic findings of Coxiella burnetii infection are variable and can be deceiving. These are often nonspecific, especially in its persistent localized infectious stages.

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Ensembling Variable Selectors by Stability Selection for the Cox Model

As a pivotal tool to build interpretive models, variable selection plays an increasingly important role in high-dimensional data analysis. In recent years, variable selection ensembles (VSEs) have gained much interest due to their many advantages. Stability selection (Meinshausen and Bühlmann, 2010), a VSE technique based on subsampling in combination with a base algorithm like lasso, is an effective method to control false discovery rate (FDR) and to improve selection accuracy in linear regression models. By adopting lasso as a base learner, we attempt to extend stability selection to handle variable selection problems in a Cox model. According to our experience, it is crucial to set the regularization region in lasso and the parameter properly so that stability selection can work well. To the best of our knowledge, however, there is no literature addressing this problem in an explicit way. Therefore, we first provide a detailed procedure to specify and . Then, some simulated and real-world data with various censoring rates are used to examine how well stability selection performs. It is also compared with several other variable selection approaches. Experimental results demonstrate that it achieves better or competitive performance in comparison with several other popular techniques.

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HIV among Female Sex Workers in Five Cities in Burkina Faso: A Cross-Sectional Baseline Survey to Inform HIV/AIDS Programs

Background. Female sex workers (FSWs) are considered a vulnerable population for HIV infection and a priority for HIV/AIDS response programs. This study aimed to determine HIV prevalence among FSWs in five cities in Burkina Faso. Methods. FSWs aged 18 and older were recruited using respondent driven sampling (RDS) in five cities (Ouagadougou, Bobo-Dioulasso, Koudougou, Ouahigouya, and Tenkodogo) in Burkina Faso from 2013 to 2014. HIV testing was performed using the HIV testing national algorithm. We conducted bivariate and multivariate logistic regression analysis to assess correlates of HIV in all cities combined (not RDS-adjusted). Results. Among Ouagadougou, Koudougou, and Ouahigouya FSWs, RDS-adjusted HIV prevalence was 13.5% (95% Confidence Interval [CI]: 9.6–18.7), 13.3% (95% CI: 7.6–22.4), and 13.0% (95% CI: 7.6–21.3), respectively, compared to 30.1% (95% CI: 25.5–35.1) among Bobo-Dioulasso FSWs. Factors associated with HIV infection were age (adjusted odds ratio [aOR] = 7.84 95% CI: 3.78–16.20), being married or cohabitating (aOR = 2.43, 95% CI: 1.31–4.49), and history of pregnancy (aOR = 5.24, 95% CI: 1.44–18.97). Conclusion. These results highlight the need to strengthen HIV prevention among FSWs, through behavior change strategies, and improve access to sexual and reproductive health services.

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Exposure to Workplace Bullying: The Role of Coping Strategies in Dealing with Work Stressors

Studies investigating both work- and individual-related antecedents of workplace bullying are scarce. In reply, this study investigated the interaction between workload, job insecurity, role conflict, and role ambiguity (i.e., work-related antecedents), and problem- and emotion-focused coping strategies (i.e., individual-related antecedents) in association with exposure to workplace bullying. Problem-focused coping strategies were hypothesised to decrease (i.e., buffer) the associations between workload, job insecurity, role conflict, and role ambiguity and exposure to bullying, while emotion-focused coping strategies were hypothesised to increase (i.e., amplify) these associations. Results for a heterogeneous sample ( = 3,105) did not provide evidence for problem-focused coping strategies as moderators. As expected, some emotion-focused coping strategies amplified the associations between work-related antecedents and bullying: employees using “focus on and venting of emotions” or “behavioural disengagement” in dealing with job insecurity, role conflict, or role ambiguity were more likely to be exposed to bullying. Similarly, “seeking social support for emotional reasons” and “mental disengagement” amplified the associations of role ambiguity and the associations of both role conflict and role ambiguity, respectively. To prevent bullying, organisations may train employees in tempering emotion-focused coping strategies, especially when experiencing job insecurity, role conflict, or role ambiguity.

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Effects of Equipment-Structure-Soil Interaction on Seismic Response of Equipment and Structure via Real-Time Dynamic Substructuring Shaking Table Testing

Equation of motion for an equipment-structure-soil (ESS) interaction system was derived using the branch substructure method. After rearrangement, this equation was applied to real-time dynamic substructuring shaking table (RTDSST) testing of the ESS system. This method adopts the equipment-structure (ES) subsystem as the experimental substructure and a modal reduced soil model as the numerical substructure: the former is tested via the shaking table, and the latter is numerically simulated, while real-time data communication occurs between the two substructures during testing. A scale model of the ESS system was designed and underwent an RTDSST test. The experimental data were found to be consistent with the numerical calculation results, which corroborates the reliability and validity of the proposed testing method. A comparison of the experimental results from different earthquake stages implies that seismic responses of the equipment and structure decreased in general due to the intervention of soil, but the soil effect weakened with earthquake intensity.

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Households’ Preference for Local Rice in the Upper East Region, Ghana

Considering the increasing demand in the rice industry, the study was undertaken to determine the factors influencing household preference for locally produced rice in the Upper East Region, Ghana. Primary data was obtained from a sample of 180 households with the aid of a structured questionnaire. Probit model and Kendall’s coefficient of concordance were used to analyze the data. Significant socioeconomic factors include income, age, sex, and marital status, whereas the quality factors such as the absence of foreign materials, packaging, and aroma were also significant determinants of preference for local rice. The top three traits consumers consider in their choice for local rice were good-looking grains, excellent packaging, and absence of foreign materials in the rice. There was an evidence of an increased preference for quality local rice. Hence, increased investment in the rice value chain, particularly the processing stage where quality standards remain the topmost priority, will help boost consumers’ confidence in the local rice market.

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Prediction of Natural Gas Consumption in Different Regions of China Using a Hybrid MVO-NNGBM Model

The accurate and reasonable prediction of natural gas consumption is significant for the government to formulate energy planning. To this end, we use the multiverse optimizer (MVO) algorithm to optimize the parameters of the Nash nonlinear grey Bernoulli model (NNGBM (1,1)) and propose a hybrid MVO-NNGBM model to predict the natural gas consumption in 30 regions of China. The results indicate that the prediction precision of the hybrid MVO-NNGBM model is better than that of other grey-based models. According to the forecast results, China’s natural gas consumption will grow rapidly over the next five years and reach 354.1 billion cubic meters (bcm) by 2020. Moreover, the spatial distribution of natural gas consumption will shift from being supply oriented towards being demand driven and will be mainly concentrated in coastal and developed provinces.

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ZnCl2 Incorporated into Experimental Adhesives: Selected Physicochemical Properties and Resin-Dentin Bonding Stability

The aim of this study was to evaluate the degree of conversion (DC%), water sorption (WS), solubility (SO), and resin-dentin bonding stability of experimental adhesive systems containing ZnCl2. Different concentrations (wt.%) of ZnCl2 were added to a model etch-and-rinse adhesive system consisting of BISGMA, HEMA, UDMA, GDMA, water, and ethanol: Zn0 (0%-control group); Zn2 (2%); Zn3.5 (3.5%); and Zn5 (5%). Adper Single Bond 2 (SB) was used as commercial reference. The samples were light cured for 20s using a quartz-tungsten-halogen unit (650 mW/cm2). DC% () was measured using FT-IR spectroscopy, and WS and SO () were calculated based on ISO4049. Microtensile bond strength (μTBS) and nanoleakage (NL) were measured after 24 h and 12 months of water storage (). Data were analyzed using ANOVA and Tukey’s HSD test (5%). Zn5 presented the lowest DC% and the highest WS and SO (). Zn0 and Zn2 presented statistically similar DC%, WS, SO, and immediate μTBS. All adhesives containing ZnCl2 maintained a μTBS stability after 12 months, but only Zn2 and Zn3.5 did not suffer an increase in NL. SB presented the highest immediate μTBS but the greatest reduction after 12 months (). The addition of 2 wt.% of ZnCl2 in adhesive formulations seems to be a promising way to improve the resin-dentin bonding stability. Higher concentrations than 2 wt.% could impair some physicochemical properties.

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Protective Effect of Yang Mi Ryung® Extract on Noise-Induced Hearing Loss in Mice

Noise-induced hearing loss (NIHL) results from the damage of the delicate hair cells inside the ear after excessive stimulation of noise. Unlike certain lower animals such as amphibians, fishes, and birds, in humans, hair cells cannot be regenerated once they are killed or damaged; thus, there are no therapeutic options to cure NIHL. Therefore, it is more important to protect hair cells from the noise before the damage occurs. In this study, we report the protective effect of Yang Mi Ryung extract (YMRE) against NIHL; this novel therapeutic property of YMRE has not been reported previously. Our data demonstrates that the hearing ability damaged by noise is markedly restored in mice preadministrated with YMRE before noise exposure, to the level of normal control group. Our study also provides the molecular mechanism underlying the protective effect of YMRE against NIHL by showing that YMRE significantly blocks noise-induced apoptotic cell death and reduces reactive oxygen species (ROS) production in cochleae. Moreover, quantitative polymerase chain reaction (qPCR) analysis demonstrates that YMRE has anti-inflammatory properties, suppressing the mRNA levels of TNFα and IL-1β induced by noise exposure. In conclusion, YMRE could be a useful preventive intervention to prevent hearing impairment induced by the exposure to excessive noise.

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The constant threat from a non-native predator increases tail muscle and fast-start swimming performance in Xenopus tadpoles [RESEARCH ARTICLE]

Tsukasa Mori, Yukio Yanagisawa, Yoichiro Kitani, Goshi Yamamoto, Naoko Goto-Inoue, Tadashi Kimura, Keiko Kashiwagi, and Akihiko Kashiwagi

Predator-induced phenotypic plasticity is the ability of prey to adapt to their native predator. However, owing to environmental changes, encounters with unknown predators are inevitable. Therefore, study of prey and non-native predator interaction will reveal the primary stages of adaptive strategies in prey-predator interactions in the context of evolutionary processes. Here, Xenopus tadpoles exposed to a non-native predator, a larval salamander, showed a significant increase in body weight and tail length to body length ratio. The T_max² test indicated a significant enhancement of the tail muscle and decrease in the relative ventral fin height in tadpoles exposed to predation risk, leading to significantly higher average swimming speeds. The analysis of muscle-related metabolites revealed that sarcosine increased significantly in tadpoles exposed to non-native predators. Multiple linear regression analysis of the fast-start swimming pattern showed that the fast-start swimming speed was determined by the time required for a tadpole to bend its body away from the threat (C-start) and the angle at which it was bent. In conclusion, morphological changes in tadpoles were functionally adaptive and induced by survival behaviors of Xenopus tadpoles against non-native predators.

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Light regimes differentially affect baseline transcript abundance of stress-axis and (neuro)development-related genes in zebrafish (Danio rerio, Hamilton 1822) AB and TL larvae [RESEARCH ARTICLE]

Ruud van den Bos, Jan Zethof, Gert Flik, and Marnix Gorissen

Many strains of zebrafish (Danio rerio) are readily available. Earlier we observed differences between AB and Tupfel long-fin (TL) larvae regarding baseline hypothalamus-pituitary-interrenal (HPI) axis activity and (neuro)development. Light regimes, i.e. 14 h light:10 h dark and 24 h continuous dark or light, affect hatching rate and larval growth. Here, we assessed baseline transcript abundance of HPI-axis-related genes and (neuro)development-related genes of AB and TL larvae (5 days post fertilisation) using these light regimes. A principal component analysis revealed that in AB larvae the baseline expression of HPI-axis-related genes was higher the more hours of light, while the expression of (neuro)development-related genes was higher under 14 h light:10 h dark than under both continuous light or dark. In TL larvae, a complex pattern emerged regarding baseline expression of HPI-axis-related and (neuro)development-related genes. These data extend data of earlier studies by showing that light regimes affect gene-expression in larvae, and more importantly so, strengthen the notion of differences between larvae of the AB and TL strain. The latter finding adds to the growing database of phenotypical differences between zebrafish of the AB and TL strain.

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MCAM contributes to the establishment of cell autonomous polarity in myogenic and chondrogenic differentiation [RESEARCH ARTICLE]

Artal Moreno-Fortuny, Laricia Bragg, Giulio Cossu, and Urmas Roostalu

Cell polarity has a fundamental role in shaping the morphology of cells and growing tissues. Polarity is commonly thought to be established in response to extracellular signals. Here we used a minimal in vitro assay that enabled us to monitor the determination of cell polarity in myogenic and chondrogenic differentiation in the absence of external signalling gradients. We demonstrate that the initiation of cell polarity is regulated by melanoma cell adhesion molecule (MCAM). We found highly polarized localization of MCAM, Moesin (MSN), Scribble (SCRIB) and Van-Gogh-like 2 (VANGL2) at the distal end of elongating myotubes. Knockout of MCAM or elimination of its endocytosis motif does not impair the initiation of myogenesis or myoblast fusion, but prevents myotube elongation. MSN, SCRIB and VANGL2 remain uniformly distributed in MCAM knockout cells. We show that MCAM is also required at early stages of chondrogenic differentiation. In both myogenic and chondrogenic differentiation MCAM knockout leads to transcriptional downregulation of Scrib and enhanced MAP kinase activity. Our data demonstrates the importance of cell autonomous polarity in differentiation.

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Selector genes display tumor cooperation and inhibition in Drosophila epithelium in a developmental context-dependent manner [RESEARCH ARTICLE]

Ram Prakash Gupta, Anjali Bajpai, and Pradip Sinha

During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey), and the segment selector, Ultrabithorax (Ubx), readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth), and/or the Zinc-finger protein, Teashirt (Tsh). In non-Hth/Tsh-expressing domains of these imaginal discs, however, gain of Ey in lgl^– somatic clones induces neoplastic transformation in the distal wing disc and haltere, but not in the eye imaginal disc. Likewise, gain of Ubx in lgl^– somatic clones induces transformation in the eye imaginal disc but not in its endogenous domain, namely, the haltere imaginal disc. Our results reveal that selector genes could behave as tumor drivers or inhibitors depending on the tissue contexts of their gains.

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Characterization and analysis of CCR and CAD gene families at the whole-genome level for lignin synthesis of stone cells in pear (Pyrus bretschneideri) fruit [RESEARCH ARTICLE]

Xi Cheng, Manli Li, Dahui Li, Jinyun Zhang, Qing Jin, Lingling Sheng, Yongping Cai, and Yi Lin

The content of stone cells has significant effects on the flavour and quality of pear fruit. Previous research suggested that lignin deposition is closely related to stone cell formation. In the lignin biosynthetic pathway, cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD), dehydrogenase/reductase family members, catalyse the last two steps in monolignol synthesis. However, there is little knowledge of the characteristics of the CCR and CAD families in pear and their involvement in lignin synthesis of stone cells. In this study, 31 CCRs and 26 CADs were identified in the pear genome. Phylogenetic trees for CCRs and CADs were constructed; key amino acid residues were analysed, and three-dimensional structures were predicted. Using quantitative real-time polymerase chain reaction (qRT-PCR), PbCAD2, PbCCR1, -2 and -3 were identified as participating in lignin synthesis of stone cells in pear fruit. Subcellular localization analysis showed that the expressed proteins (PbCAD2, PbCCR1, -2 and -3) are found in the cytoplasm or at the cell membrane. These results reveal the evolutionary features of the CCR and CAD families in pear as well as the genes responsible for regulation of lignin synthesis and stone cell development in pear fruit.

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Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin {beta}1 in endothelial cells [RESEARCH ARTICLE]

Masashi Maekawa, Kazufumi Tanigawa, Tomohisa Sakaue, Hiromi Hiyoshi, Eiji Kubota, Takashi Joh, Yuji Watanabe, Tomohiko Taguchi, and Shigeki Higashiyama

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is related to numerous pathophysiological events. We previously reported that a RING ubiquitin ligase complex scaffold protein, cullin-3 (CUL3), and one of its adaptor proteins, BAZF, regulated angiogenesis in the mouse retina by suppressing Notch signaling. However, the degree of inhibition of angiogenesis was made greater by CUL3 depletion than by BAZF depletion, suggesting other roles of CUL3 in angiogenesis besides the regulation of Notch signaling. In the present study, we found that CUL3 was critical for the cell surface level of integrin β1, an essential cell adhesion molecule for angiogenesis in HUVECs. By siRNA screening of 175 BTBPs, a family of adaptor proteins for CUL3, we found that ANKFY1/Rabankyrin-5, an early endosomal BTBP, was also critical for localization of surface integrin β1 and angiogenesis. CUL3 interacted with ANKFY1 and was required for the early endosomal localization of ANKFY1. These data suggest that CUL3/ANKFY1 regulates endosomal membrane traffic of integrin β1. Our results highlight the multiple roles of CUL3 in angiogenesis, which are mediated through distinct CUL3-adaptor proteins.

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Release of condensin from mitotic chromosomes requires the Ran-GTP gradient in the reorganized nucleus [RESEARCH ARTICLE]

Keita Aoki and Hironori Niki

After mitosis, nuclear reorganization occurs together with decondensation of mitotic chromosomes and reformation of the nuclear envelope, thereby restoring the Ran-GTP gradient between the nucleus and cytoplasm. The Ran-GTP gradient is dependent on Pim1/RCC1. Interestingly, a defect in Pim1/RCC1 in Schizosaccharomyces pombe causes postmitotic condensation of chromatin, namely hypercondensation, suggesting a relationship between the Ran-GTP gradient and chromosome decondensation. However, how Ran-GTP interacts with chromosome decondensation is unresolved. To examine this interaction, we used Schizosaccharomyces japonicus, which is known to undergo partial breakdown of the nuclear membrane during mitosis. We found that Pim1/RCC1 was localized on nuclear pores, but this localization failed in a temperature-sensitive mutant of Pim1/RCC1. The mutant cells exhibited hypercondensed chromatin after mitosis due to prolonged association of condensin on the chromosomes. Conceivably, a condensin-dephosphorylation defect might cause hypercondensed chromatin, since chromosomal localization of condensin is dependent on phosphorylation by cyclin-dependent kinase (CDK). Indeed, CDK-phospho-mimic mutation of condensin alone caused untimely condensin localization, resulting in hypercondensed chromatin. Together, these results suggest that dephosphorylation of CDK sites of condensin might require the Ran-GTP gradient produced by nuclear pore-localized Pim1/RCC1.

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Differential expression of STAT-3 in subtypes of oral lichen planus: a preliminary study

Publication date: Available online 14 November 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Guanhuan Du, Junjun Chen, Yanni Wang, Tianyi Cao, Leilei Zhou, Yufeng Wang, Xiaozhe Han, Guoyao Tang
Objective.This study aimed to examine the expression of signaling transduction proteins and their possible correlation with different clinical subtypes of oral lichen planus (OLP).Study design.We examined the immunoexpression and phosphorylation status of 21 signaling transduction proteins of OLP (n=10) and normal groups (n=8) using PathScan® analysis. We detected expression of STAT-3 and p38MAPK in tissues of OLP (n=40) and normal groups (n=10) by immunohistochemistry.Results.PathScan® analysis showed that STAT-3(Ser727) expression in normal control (N), reticular OLP (R-OLP) and erosive OLP (E-OLP) group was gradually elevated (R-OLP vs N, P=0.001; E-OLP vs N, P<0.001; E-OLP vs R-OLP, P=0.002). Immunohistochemistry showed that STAT-3 expression in the epithelium of normal control, reticular OLP and erosive OLP was consistent with PathScan® analysis (R-OLP vs N, P<0.001; E-OLP vs N, P<0.001; E-OLP vs R-OLP, P=0.036). Both PathScan® (P=0.012) and immunohistochemistry (P<0.001) showed that, p38MAPK expression was significantly higher than normal controls. However, a significant difference was not seen between reticular OLP and erosive OLP groups.Conclusions.Our results provide information indicating that STAT-3 may be involved in OLP development and progression and account for different clinical manifestations.



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Patients' osteometabolic control improves the management of medication-related osteonecrosis of the jaw.

Publication date: Available online 14 November 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Gianluca Colapinto, Raffaele Volpi, Giovanni Forino, Vito Tricarico, Michele De Benedittis, Roberto Cortelazzi, Tiziano Testori, Massimo Del Fabbro
Objectives.Osteonecrosis of the jaws (ONJ) represents a concern for patients taking antiresorptive drugs. The aim of this study was to test the hypothesis that preoperative individualized pharmacological control of the patient's osteometabolic profile could lead to predictable healing of the surgically treated region and minimize the incidence of complications.Study Design.This prospective study included 95 test patients (53 with osteoporosis and 42 with cancer), and 94 control patients (49 with osteoporosis and 45 with cancer) who were on antiresorptive therapy and were candidates for ONJ treatment. Test patients underwent osteometabolic profile assessment and personalized pharmacological supplementation before intervention. In all cases, a drug holiday was scheduled for three months before and at least three months after the intervention. Healing was assessed clinically and radiographically.Results.In the test group, after a mean follow-up of 28.2±7.8 months only one ONJ recurrence occurred, and was successfully resolved after resuming the pharmacological protocol. Five patients reported minor complications. Overall, 100% treatment success was observed. In the control group, after 28.1±4.9 months follow-up, 6 fistulae, 19 abscesses and 34 dehiscences occurred. In total, 62.8% of patients in the control group had complications or adverse events. The difference between the two groups was highly significant.Conclusions.A strict osteometabolic control should be routinely done in the management of patients taking antiresorptive drugs.



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Relationships between temporomandibular joint disc displacements and condylar volume

Publication date: Available online 14 November 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Min-Seok Chang, Jeong-Ho Choi, Il-Hyung Yang, Jung-Sub An, Min-Suk Heo, Sug-Joon Ahn
Objectives.We aimed to assess the relationship between mandibular condylar volume and disc displacement status, in male and female adults.Study Design.We evaluated 122 temporomandibular joints in 61 subjects, using magnetic resonance imaging (MRI) and computed tomography (CT). MRI data were used to assign disk status as either normal disk position (NR), disk displacement with reduction (DDR), or disk displacement without reduction (DDNR). CT data were used to calculate total condylar volume and its components, cortical volume and trabecular volume. The relationships between condylar volume, and disk status, and gender were tested with two-way analysis of variance.Results.Condylar volumes significantly correlated with disc displacement, tending to decrease as displacement increased. There were significant differences in both total condylar volume and trabecular volume among the DD status (NR > DDR > DDNR), while cortical volume were significantly different only between NR or DDR and DDNR (NR, DDR > DDNR). The volume decreases associated with TMJ DD were found in both males and females, with greater decreases in men than in women as DD progressed.Conclusion.Condylar volumes are significantly associated with disc displacement status. Joints with non-reducing discs showed the smallest condylar volumes in both males and females.



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Juvenile Type of Generalized Ceroid-Lipofuscinosis (Spielmeyer-Sjögren Syndrome), I. Clinical Findings

Thirteen patients with the clinical course of the juvenile type of generalized ceroid-lipofuscinosis were examined clinically, ophthalmologically, neurologically and psychiatrically. This included registration of EEG, x-ray, brain scintigraphy, motor nerve conduction velocity, ERG, fundus photography and bioptical investigations including electron microscopy. The children suffered from progressing decrease of visual acuity, decline of mental capacities, and later on speech and gait disturbances. The most characteristic findings are presented in case reports, two tables and fourteen pictures.

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A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Eric Angevin, Gianluca Spitaleri, Jordi Rodon, Katia Dotti, Nicolas Isambert, Stefania Salvagni, Victor Moreno, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Antoine Hollebecque, Analia Azaro, Alice Hervieu, Karim Rihawi, Filippo De Marinis
PurposeDysregulated MET signalling is implicated in oncogenesis. The safety and preliminary efficacy of a highly selective MET kinase inhibitor (SAR125844) was investigated in patients with advanced solid tumours and MET dysregulation.MethodsThis was a phase I dose-escalation (3 + 3 design [50–740 mg/m²]) and dose-expansion study. In the dose escalation, patients had high total MET (t-MET) expression by immunohistochemistry (IHC) or MET amplification by fluorescence in situ hybridisation. In the dose expansion, patients had MET amplification (including a subset of patients with non-small cell lung cancer [NSCLC]) or phosphorylated-MET (p-MET) expression (IHC). Objectives were determination of maximum tolerated dose (MTD) of once-weekly intravenous SAR125844 based on dose-limiting toxicities; safety and pharmacokinetic profile; preliminary efficacy of SAR125844 MTD in the expansion cohort.ResultsIn total, 72 patients were enrolled: dose escalation, N = 33; dose expansion, N = 39; 570 mg/m² was established as the MTD. Most frequent treatment-emergent adverse events (AEs) were asthenia/fatigue (58.3%), nausea (31.9%), and abdominal pain, constipation, and dyspnea (27.8% for each); 58.3% of patients reported grade 3 AEs (19.4% were treatment related). Of the 29 evaluable patients with MET amplification treated at 570 mg/m², five achieved a partial response, including four of 22 with NSCLC; 17 patients had stable disease. No response was observed in patients with high p-MET solid tumours. There was no correlation between tumour response and t-MET status or MET gene copy number.ConclusionThe MTD of once-weekly SAR125844 was 570 mg/m²; SAR125844 was well tolerated, with significant antitumour activity in patients with MET-amplified NSCLC.Clinical trial registration number: NCT01391533



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Precision medicine for patients with advanced biliary tract cancers: An effective strategy within the prospective MOSCATO-01 trial

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Loic Verlingue, David Malka, Adrien Allorant, Christophe Massard, Charles Ferté, Ludovic Lacroix, Etienne Rouleau, Nathalie Auger, Maud Ngo, Claudio Nicotra, Thierry De Baere, Lambros Tselikas, Bakar Ba, Stefan Michiels, Jean-Yves Scoazec, Valérie Boige, Michel Ducreux, Jean-Charles Soria, Antoine Hollebecque
BackgroundRecommended treatments of patients with advanced biliary tract cancer (aBTC) are limited to one chemotherapy doublet. Nevertheless, efficacy of treatment personalisation for aBTCs is supported by accumulating evidences but remains to be evaluated.Patients and methodsPatients with aBTCs included in the prospective clinical trial MOSCATO-01 were treated by at least one previous systemic treatment, had an ECOG performance status of 0–1, and at least one tumour site accessible to biopsy. Multiple high-throughput molecular analysis was performed on biopsies to drive the administration of molecular targeted agents (MTAs).ResultsFrom November 2011 to March 2016, 43 patients (4%) of the 1035 adult patients included in MOSCATO-01 had aBTCs with a majority of intrahepatic localisation (67%). Successful biopsy procedures and DNA extractions led to molecular portraits for 34 patients (79%). Orientation to an appropriate early clinical trial or accessible MTA(s) was possible for 23 of these patients (68%), and 18 (53%) have received matched MTA(s). Among them, the overall response rate was 33% and the disease control rate was 88%. A PFS ≥6 months was observed in 37% and the PFS ratio was >1.3 for 50% of the patients. These patients had a lower risk for death as compared to the 20 patients not orientated to a matched MTA (HR, 0.29; 95% CI, 0.11–0.76; p = 0.008).ConclusionsWithin the MOSCATO-01 trial, patients with aBTCs had the highest rate of orientation to matched MTAs and derived a clear clinical benefit. A broader evaluation of these findings may improve future treatments strategies for aBTCs.Trial Registration: NCT01566019.



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Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Y. Loriot, L. Pagliaro, A. Fléchon, J. Mardiak, L. Geoffrois, P. Kerbrat, C. Chevreau, R. Delva, F. Rolland, C. Theodore, G. Roubaud, G. Gravis, J.C. Eymard, J.P. Malhaire, C. Linassier, M. Habibian, A.L. Martin, F. Journeau, M. Reckova, C. Logothetis, A. Laplanche, G. Le Teuff, S. Culine, K. Fizazi
BackgroundThe GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13.MethodsWe conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain.ResultsWith a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy.ConclusionsBrain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2–3 months of chemotherapy.



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