Πέμπτη, 4 Ιανουαρίου 2018

Upfront vs. no upfront neck dissection in primary head and neck cancer radio(chemo)therapy: Reply to Elicin et al.

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Publication date: Available online 4 January 2018
Source:Radiotherapy and Oncology
Author(s): Daan Nevens, Fréderic Duprez, Katrien Bonte, Philippe Deron, Wouter Huvenne, Annouschka Laenen, Wilfried De Neve, Sandra Nuyts




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Thoron exposure in Dutch dwellings – An overview

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Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): G. de With, R.C.G.M. Smetsers, H. Slaper, P. de Jong
In the Netherlands considerable attention has been given to the exposure from thoron progeny in dwellings. For this purpose a nationwide survey on the thoron exhalation and thoron progeny concentration has been completed in 2015. Furthermore, extensive laboratory studies have been performed to measure activity concentrations and thoron exhalation rates from regular Dutch building materials. The purpose of this study is to demonstrate if the findings from both field experiments and laboratory results are consistent. For this reason measured properties of building materials and surface barriers, in-situ measurements on air ventilation and thoron(progeny) in dwellings as well as advanced computational modelling on indoor air and aerosol behaviour have been used. The results demonstrate that median and mean thoron progeny concentrations of 0.53 and 0.64 Bq·m−3 found in the survey are comparable with the mean concentration of 0.57 Bq·m−3 obtained from laboratory testing and calculation. Furthermore, upper thoron progeny concentrations from the survey and the calculations are with respectively 13 and 14 Bq·m−3 also in good agreement. Such elevated concentrations lead to an effective doses of around 4 mSv per year. The study also includes worst-case scenarios on the application of surface materials high on 232Th, and the expected reduction in thoron progeny when using mainstream mitigation measures.



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Inventory and vertical distribution of 137Cs, 239+240Pu and 238Pu in soil from Raivavae and Hiva Oa, two French Polynesian islands in the southern hemisphere

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Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): P. Bouisset, M. Nohl, A. Bouville, G. Leclerc
Atmospheric nuclear weapons tests carried out by the United States, the former Soviet Union, the United Kingdom, France and China between 1945 and 1980 resulted in radioactive fallout over the earth's surface of long-lived radionuclides, such as 137Cs, 239+240Pu and 238Pu that could be detected more than 50 years after their production. In addition, the burnup in the upper atmosphere of a thermoelectric generator fueled by 238Pu, SNAP-9A, contributed to the inventory of 238Pu deposited on the ground. In order to estimate the deposition densities of 137Cs, 239+240Pu and 238Pu in French Polynesia, we collected undisturbed soil samples up to 30 cm deep at eight sites in two islands (Hiva Oa, 139°W - 10°S and Raivavae, 148°W - 24°S) in 2015–2016. The top 0–10 cm of the soil cores were sliced into five 2-cm layers and the bottom 10–30 cm into four 5-cm layers for gamma spectrometry and alpha spectrometry measurements. We found that more than 50% of the radioactive inventories are still contained within the first 10 cm and that the average vertical migration velocities of 137Cs and Pu are less than 0.2 cm y−1. The average accumulated depositions, deduced from the profile measurements, are 236 ± 11 Bq.m−2 and 313 ± 39 Bq.m−2 for 137Cs, 12.1 ± 1.5 Bq.m−2 and 22.1 ± 1.7 Bq.m−2 for 239+240Pu, and 1.23 ± 0.46 Bq.m−2 and 1.58 ± 0.60 Bq.m−2 for 238Pu, in Hiva Oa and Raivavae, respectively. The 238Pu/239+240Pu ratios are 0.102 ± 0.050 at Hiva Oa and 0.072 ± 0.033 at Raivavae. Both values are higher than the ratio in nuclear weapons tests fallout estimated to be 0.016 in 2016 (Hardy et al., 1973), because of the contribution of 238Pu fallout from SNAP-9A, which is latitude dependent. The 137Cs/239+240Pu ratios, 19.5 ± 3.2 at Hiva Oa and 14.2 ± 2.8 at Raivavae are in the lower part of the range of values observed in other regions of the world.



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Cone beam CT of the musculoskeletal system: clinical applications

Abstract

Objectives

The aim of this pictorial review is to illustrate the use of CBCT in a broad spectrum of musculoskeletal disorders and to compare its diagnostic merit with other imaging modalities, such as conventional radiography (CR), Multidetector Computed Tomography (MDCT) and Magnetic Resonance Imaging.

Background

Cone Beam Computed Tomography (CBCT) has been widely used for dental imaging for over two decades.

Discussion

Current CBCT equipment allows use for imaging of various musculoskeletal applications. Because of its low cost and relatively low irradiation, CBCT may have an emergent role in making a more precise diagnosis, assessment of local extent and follow-up of fractures and dislocations of small bones and joints. Due to its exquisite high spatial resolution, CBCT in combination with arthrography may be the preferred technique for detection and local staging of cartilage lesions in small joints. Evaluation of degenerative joint disorders may be facilitated by CBCT compared to CR, particularly in those anatomical areas in which there is much superposition of adjacent bony structures. The use of CBCT in evaluation of osteomyelitis is restricted to detection of sequestrum formation in chronic osteomyelitis. Miscellaneous applications include assessment of (symptomatic) variants, detection and characterization of tumour and tumour-like conditions of bone.

Teaching Points

• Review the spectrum of MSK disorders in which CBCT may be complementary to other imaging techniques.

• Compare the advantages and drawbacks of CBCT compared to other imaging techniques.

• Define the present and future role of CBCT in musculoskeletal imaging.



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"Delayed Pial Vessels" in Multiphase CT Angiography Aid in the Detection of Arterial Occlusion in Anterior Circulation [LETTERS]



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Reply: [LETTERS]



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Diffusion-Weighted Imaging of Brain Metastasis from Lung Cancer: Correlation of MRI Parameters with the Histologic Type and Gene Mutation Status [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Development of noninvasive imaging biomarkers indicating the histology and the gene mutation status of brain metastasis from lung cancer is important. We aimed to investigate diffusion-weighted imaging parameters as predictors of the histology and gene mutations of brain metastasis from lung cancer.

MATERIALS AND METHODS:

DWI data for 74 patients with brain metastasis from lung cancer were retrospectively reviewed. The patients were first grouped according to the primary tumor histology (adenocarcinoma, small-cell lung cancer, squamous cell carcinoma), and those with adenocarcinoma were further divided into epidermal growth factor receptor (EFGR) mutation–positive and wild type groups. Sex; age; number, size, and location of brain metastasis; DWI visual scores; the minimum ADC; and the normalized ADC ratio were compared among groups using 2 and ANOVA. Multiple logistic regression analysis was performed to determine independent predictors of the EGFR mutation.

RESULTS:

The minimum ADC was lower in the small-cell lung cancer group than in the other 2 groups, though the difference was not significant. Furthermore, minimum ADC and the normalized ADC ratio were significantly lower in the EGFR mutation–positive group than in the wild type group (P = .021 and .014, respectively). Multivariate analysis revealed that minimum ADC and the normalized ADC ratio were independently associated with the EGFR mutation status (P = .028 and .021, respectively).

CONCLUSIONS:

Our results suggest that DWI parameters (minimum ADC and normalized ADC ratio) for the solid components of brain metastasis from lung cancer are not correlated with their histology, whereas they can predict the EGFR mutation status in brain metastasis from lung adenocarcinoma.



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What Have We Learned from MR Imaging in Multiple Sclerosis? [REVIEW ARTICLE]

SUMMARY:

Using MR imaging, perfusion can be assessed either by dynamic susceptibility contrast MR imaging or arterial spin-labeling. Alterations of cerebral perfusion have repeatedly been described in multiple sclerosis compared with healthy controls. Acute lesions exhibit relative hyperperfusion in comparison with normal-appearing white matter, a finding mostly attributed to inflammation in this stage of lesion development. In contrast, normal-appearing white and gray matter of patients with MS has been mostly found to be hypoperfused compared with controls, and correlations with cognitive impairment as well as fatigue in multiple sclerosis have been described. Mitochondrial failure, axonal degeneration, and vascular dysfunction have been hypothesized to underlie the perfusion MR imaging findings. Clinically, perfusion MR imaging could allow earlier detection of the acute focal inflammatory changes underlying relapses and new lesions, and could constitute a marker for cognitive dysfunction in MS. Nevertheless, the clinical relevance and pathogenesis of the brain perfusion changes in MS remain to be clarified.



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Addition of Amide Proton Transfer Imaging to FDG-PET/CT Improves Diagnostic Accuracy in Glioma Grading: A Preliminary Study Using the Continuous Net Reclassification Analysis [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Amide proton transfer imaging has been successfully applied to brain tumors, however, the relationships between amide proton transfer and other quantitative imaging values have yet to be investigated. The aim was to examine the additive value of amide proton transfer imaging alongside [18F] FDG-PET and DWI for preoperative grading of gliomas.

MATERIALS AND METHODS:

Forty-nine patients with newly diagnosed gliomas were included in this retrospective study. All patients had undergone MR imaging, including DWI and amide proton transfer imaging on 3T scanners, and [18F] FDG-PET. Logistic regression analyses were conducted to examine the relationship between each imaging parameter and the presence of high-grade (grade III and/or IV) glioma. These parameters included the tumor-to-normal ratio of FDG uptake, minimum ADC, mean amide proton transfer value, and their combinations. In each model, the overall discriminative power for the detection of high-grade glioma was assessed with receiver operating characteristic curve analysis. Additive information from minimum ADC and mean amide proton transfer was also evaluated by continuous net reclassification improvement. P < .05 was considered significant.

RESULTS:

Tumor-to-normal ratio, minimum ADC, and mean amide proton transfer demonstrated comparable diagnostic accuracy in differentiating high-grade from low-grade gliomas. When mean amide proton transfer was combined with the tumor-to-normal ratio, the continuous net reclassification improvement was 0.64 (95% CI, 0.036–1.24; P = .04) for diagnosing high-grade glioma and 0.95 (95% CI, 0.39–1.52; P = .001) for diagnosing glioblastoma. When minimum ADC was combined with the tumor-to-normal ratio, the continuous net reclassification improvement was 0.43 (95% CI, –0.17–1.04; P = .16) for diagnosing high-grade glioma, and 1.36 (95% CI, 0.79–1.92; P < .001) for diagnosing glioblastoma.

CONCLUSIONS:

Addition of amide proton transfer imaging to FDG-PET/CT may improve the ability to differentiate high-grade from low-grade gliomas.



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Multiparametric Analysis of Permeability and ADC Histogram Metrics for Classification of Pediatric Brain Tumors by Tumor Grade [PEDIATRICS]

BACKGROUND AND PURPOSE:

Accurate tumor grading is essential for treatment planning of pediatric brain tumors. We hypothesized that multiparametric analyses of a combination of permeability metrics and ADC histogram metrics would differentiate high- and low-grade tumors with high accuracy.

MATERIALS AND METHODS:

DTI and dynamic contrast-enhanced MR imaging using T1-mapping with flip angles of 2°, 5°, 10°, and 15°, followed by a 0.1-mmol/kg body weight gadolinium-based bolus was performed on all patients in addition to standard MR imaging. Permeability data were processed and transfer constant from the blood plasma into the extracellular extravascular space, rate constant from the extracellular extravascular space back into blood plasma, extravascular extracellular volume fraction, and fractional blood plasma volume were calculated from 3D tumor volumes. Apparent diffusion coefficient histogram metrics were calculated for 3 separate tumor volumes derived from T2-FLAIR sequences, T1 contrast-enhanced sequences, and permeability maps, respectively.

RESULTS:

Results from 41 patients (0.3–16.76 years of age; mean, 6.22 years) with newly diagnosed contrast-enhancing brain tumors (16 low-grade; 25 high-grade) were included in the institutional review board–approved retrospective analysis. Wilcoxon tests showed a higher transfer constant from blood plasma into extracellular extravascular space and rate constant from extracellular extravascular space back into blood plasma, and lower extracellular extravascular volume fraction (P < .001) in high-grade tumors. The mean ADCs of FLAIR and enhancing tumor volumes were significantly lower in high-grade tumors (P < .001). ROC analysis showed that a combination of extravascular volume fraction and mean ADC of FLAIR volume differentiated high- and low-grade tumors with high accuracy (area under receiver operating characteristic curve = 0.918).

CONCLUSIONS:

ADC histogram metrics combined with permeability metrics differentiate low- and high-grade pediatric brain tumors with high accuracy.



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Evaluation of an automated breast volume scanner according to the fifth edition of BI-RADS for breast ultrasound compared with hand-held ultrasound

Publication date: Available online 4 January 2018
Source:European Journal of Radiology
Author(s): Eun Jung Choi, HyeMi Choi, Eun Hae Park, Ji Soo Song, Ji Hyun Youk
ObjectivesTo investigate the automated breast volume scanner (ABVS) in comparison with hand-held ultrasound (HHUS) according to the fifth edition of BI-RADS ultrasound.Material and MethodsA total of 831 lesions in 786 patients who underwent both HHUS and ABVS were included. Three radiologists independently evaluated the sonographic features of each lesion according to the fifth BI-RADS edition. The kappa coefficient (κ) was calculated for each BI-RADS descriptor and final assessment category. The accuracy of malignancy prediction and diagnostic performance of the BI-RADS descriptors were assessed using multivariate logistic regression and area under the receiver operator characteristic curve (AUC), respectively.ResultsABVS and HHUS showed moderate to good interobserver agreement (κ=0.53-0.67 and 0.55-0.70, respectively) except in associated features (κ=0.31 and 0.36, respectively) for BI-RADS lexicons. Irregular shape, a non-circumscribed margin, and posterior features (combined or shadowing) were independently associated with malignancy in both ABVS and HHUS. Calcification presence on ABVS (odds ratio [OR], 95% confidence interval [CI]: 2.09, 1.11–3.94) and non-parallel orientation on HHUS (OR, 95% CI: 2.04, 1.10–3.78) were independently associated with malignancy. There were no significant differences between ABVS and HHUS in sensitivity (84.2% vs. 84.2%), specificity (80.5% vs. 83.9%), or AUC (0.88 vs. 0.90).ConclusionsAccording to the fifth BI-RADS edition, ABVS is not statistically significantly different from HHUS with regard to interobserver variability and diagnostic performance.



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Altered functional connectivity in post-ischemic stroke depression: a resting-state functional magnetic resonance imaging study

Publication date: Available online 4 January 2018
Source:European Journal of Radiology
Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zheng Song, Jianping Dai, Jun Wang
ObjectiveIn previous studies, post-stroke depression (PSD) was found to be related to stroke characteristics as well as social and psychological factors. This study identified altered functional connectivity (FC) in patients with PSD at the subacute phase in three brain networks: default mood network (DMN), cognitive control network (CCN), and affective network (AN). The correlation between FC and the severity of PSD was investigated.Materials and MethodsResting-state functional magnetic resonance image (rs-fMRI) was performed on 26 PSD patients (6 females), 24 stroke patients without depression (5 females), and 24 age-matched normal controls (6 females) all aged 40–75 years. The FC values of DMN, CCN, and AN were calculated and compared among the three groups. The Hamilton Depression Rating Scale (HDRS) (17 items) was employed and the score was correlated with FC in the PSD group.ResultsThe FCs of the three networks were altered in PSD patients at the subacute phase compared to stroke patients without depression and normal controls (NC). Moreover, the left inferior parietal gyrus, the left orbital part of inferior frontal gyrus, and left angular gyrus (which indicated altered FC) were significantly correlated with HDRS scores in PSD patients.ConclusionsAlteration of the three neural networks might be correlated with the development of PSD at the subacute phase of stroke.



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Mammography image quality and evidence based practice; analysis of the demonstration of the inframammary angle in the digital setting.

Publication date: Available online 4 January 2018
Source:European Journal of Radiology
Author(s): Kelly Spuur, Jodi Webb, Ann Poulos, Sharon Nielsen, Wayne Robinson
AimThe aim of this study is to determine the clinical rates of the demonstration of the inframammary angle (IMA) on the mediolateral oblique (MLO) view of the breast on digital mammograms and to compare the outcomes with current accreditation standards for compliance. Relationships between the IMA, age, the posterior nipple line (PNL) and compressed breast thickness will be identified and the study outcomes validated using appropriate analyses of inter-reader and inter-rater reliability and variability. Differences in left versus right data were also investigated.MethodA quantitative retrospective study of 2270 randomly selected paired digital mammograms performed by BreastScreen NSW was undertaken. Data was collected by direct measurement and visual analysis. Intra-class correlation analyses were used to evaluate inter- and intra-rater reliability.ResultsThe IMA was demonstrated on 52.4% of individual and 42.6% of paired mammograms. A linear relationship was found between the posterior nipple line (PNL) and age (p-value <0.001). The PNL was predicted to increase by 0.48 mm for every one year increment in age. The odds of demonstrating the IMA reduced by 2% for every one year increase in age (p-value = 0.001); are 0.4% higher for every 1 mm increase in PNL (p-value = 0.001) and 1.6% lower for every 1 mm increase in compressed breast thickness, (p-value<0.001). There was high inter- and intra-rater reliability for the PNL while there was 100% agreement for the demonstration of the IMA.ConclusionAnalysis of the demonstration of the IMA indicates clinically achievable rates (42.6%) well below that required for compliance (50%–75%) to known worldwide accreditation standards for screening mammography. These standards should be aligned to the reported evidence base. Visualisation of the IMA is impacted negatively by increasing age and compressed breast thickness but positively by breast size.



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Pediatric Brain: Gadolinium Deposition in Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images Is Dependent on the Type of Contrast Agent

Purpose The aim of this study was to identify the signal intensity (SI) changes in the dentate nucleus (DN) and the globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR) images after multiple administration of gadolinium-based contrast agents (GBCAs) in children and compare those changes between linear and macrocyclic GBCAs. Materials and Methods This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. We identified 92 children who underwent at least 4 consecutive MR examinations exclusively using either linear GBCA (gadodiamide or gadopentetate dimeglumine, n = 41) or macrocyclic GBCA (gadoterate meglumine, n = 51). Signal intensity ratio changes in the DN to pons and GP to thalamus between the first and last MR examinations were calculated. Results The SI ratios in the linear group increased significantly between the first and last MR examinations (mean difference: DN to pons, 0.0461 ± 0.0480, P

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Pediatric Brain: Gadolinium Deposition in Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images Is Dependent on the Type of Contrast Agent

Purpose The aim of this study was to identify the signal intensity (SI) changes in the dentate nucleus (DN) and the globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR) images after multiple administration of gadolinium-based contrast agents (GBCAs) in children and compare those changes between linear and macrocyclic GBCAs. Materials and Methods This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. We identified 92 children who underwent at least 4 consecutive MR examinations exclusively using either linear GBCA (gadodiamide or gadopentetate dimeglumine, n = 41) or macrocyclic GBCA (gadoterate meglumine, n = 51). Signal intensity ratio changes in the DN to pons and GP to thalamus between the first and last MR examinations were calculated. Results The SI ratios in the linear group increased significantly between the first and last MR examinations (mean difference: DN to pons, 0.0461 ± 0.0480, P

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Upfront vs. no upfront neck dissection in primary head and neck cancer radio(chemo)therapy: Reply to Elicin et al.

We want to thank Elicin et al. for contributing to the discussion regarding upfront neck dissection (ND) in the radiochemotherapy (RCT) setting in head and neck cancer and for their critical appraisal of our paper [1,2].

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Reducing task-based fMRI scanning time using simultaneous multislice echo planar imaging

Abstract

Purpose

To maintain alertness and to remain motionless during scanning represent a substantial challenge for patients/subjects involved in both clinical and research functional magnetic resonance imaging (fMRI) examinations. Therefore, availability and application of new data acquisition protocols allowing the shortening of scan time without compromising the data quality and statistical power are of major importance.

Methods

Higher order category-selective visual cortical areas were identified individually, and rapid event-related fMRI design was used to compare three different sampling rates (TR = 2000, 1000, and 410 ms, using state-of-the-art simultaneous multislice imaging) and four different scanning lengths to match the statistical power of the traditional scanning methods to high sampling-rate design.

Results

The results revealed that ~ 4 min of the scan time with 1 Hz (TR = 1000 ms) sampling rate and ~ 2 min scanning at ~ 2.5 Hz (TR = 410 ms) sampling rate provide similar localization sensitivity and selectivity to that obtained with 11-min session at conventional, 0.5 Hz (TR = 2000 ms) sampling rate.

Conclusion

Our findings suggest that task-based fMRI examination of clinical population prone to distress such as presurgical mapping experiments might substantially benefit from the reduced (20–40%) scanning time that can be achieved by the application of simultaneous multislice sequences.



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The Influence of Neurocognitive Impairment, Depression, and Alcohol Use Disorders on Health-Related Quality of Life among Incarcerated, HIV-Infected, Opioid Dependent Malaysian Men: A Moderated Mediation Analysis.

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The Influence of Neurocognitive Impairment, Depression, and Alcohol Use Disorders on Health-Related Quality of Life among Incarcerated, HIV-Infected, Opioid Dependent Malaysian Men: A Moderated Mediation Analysis.

AIDS Behav. 2017 Apr;21(4):1070-1081

Authors: Shrestha R, Weikum D, Copenhaver M, Altice FL

Abstract
Prior research has widely recognized neurocognitive impairment (NCI), depression, and alcohol use disorders (AUDs) as important negative predictors of health-related quality of life (HRQoL) among people living with HIV (PLWH). No studies to date, however, have explored how these neuropsychological factors operate together and affect HRQoL. Incarcerated male PLWH (N = 301) meeting criteria for opioid dependence were recruited from Malaysia's largest prison. Standardized scales for NCI, depression, alcohol use disorders (AUDs) and HRQoL were used to conduct a moderated mediation model to explore the extent to which depression mediated the relationship between NCI, HRQoL, and AUDs using an ordinary least squares regression-based path analytic framework. Results showed that increasing levels of NCI (B = -0.1773, p < 0.001) and depression (B = -0.6147, p < 0.001) were negatively associated with HRQoL. The effect of NCI on HRQoL was significantly (Sobel z = -3.5600, p < 0.001) mediated via depression (B = -0.1230, p < 0.001). Furthermore, the conditional indirect effect of NCI on HRQoL via depression for individuals with AUDs was significant (B = -0.9099, p = 0.0087), suggesting a moderated mediation effect. The findings disentangle the complex relationship using a moderated mediation model, demonstrating that increasing levels of NCI, which can be reduced with HIV treatment, negatively influenced HRQoL via depression for individuals with AUDs. This highlights the need for future interventions to target these complex interplay between neuropsychological factors in order to improve HRQoL among PLWH, particularly incarcerated PLWH with AUDs.

PMID: 27544515 [PubMed - indexed for MEDLINE]



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The changing purpose of mental health law: From medicalism to legalism to new legalism.

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The changing purpose of mental health law: From medicalism to legalism to new legalism.

Int J Law Psychiatry. 2016 Jul-Aug;47:1-9

Authors: Brown J

Abstract
The role of law in regulating mental health detention has come to engender great contention in the legal and sociological disciplines alike. This conflict is multifaceted but is centred upon the extent to which law should control the psychiatric power of detention. In this manner the evolution of law regulating mental health detention has been seen in terms of a pendulous movement between two extremes of medicalism and legalism. Drawing on socio-legal literature, legislation, international treaties and case law this article examines the changing purpose of mental health law from an English and Council of Europe perspective by utilizing the concepts of medicalism, legalism and new legalism as descriptive devices before arguing that the UN Convention on the Rights of Persons with Disabilities goes further than all of these concepts and has the potential to influence mental health laws internationally.

PMID: 27059132 [PubMed - indexed for MEDLINE]



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Development, preliminary usability and accuracy testing of the EBMT 'eGVHD App' to support GvHD assessment according to NIH criteria-a proof of concept.

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Development, preliminary usability and accuracy testing of the EBMT 'eGVHD App' to support GvHD assessment according to NIH criteria-a proof of concept.

Bone Marrow Transplant. 2016 Aug;51(8):1062-5

Authors: Schoemans H, Goris K, Durm RV, Vanhoof J, Wolff D, Greinix H, Pavletic S, Lee SJ, Maertens J, Geest SD, Dobbels F, Duarte RF

Abstract
The EBMT Complications and Quality of Life Working Party has developed a computer-based algorithm, the 'eGVHD App', using a user-centered design process. Accuracy was tested using a quasi-experimental crossover design with four expert-reviewed case vignettes in a convenience sample of 28 clinical professionals. Perceived usefulness was evaluated by the technology acceptance model (TAM) and User satisfaction by the Post-Study System Usability Questionnaire (PSSUQ). User experience was positive, with a median of 6 TAM points (interquartile range: 1) and beneficial median total, and subscale PSSUQ scores. The initial standard practice assessment of the vignettes yielded 65% correct results for diagnosis and 45% for scoring. The 'eGVHD App' significantly increased diagnostic and scoring accuracy to 93% (+28%) and 88% (+43%), respectively (both P<0.05). The same trend was observed in the repeated analysis of case 2: accuracy improved by using the App (+31% for diagnosis and +39% for scoring), whereas performance tended to decrease once the App was taken away. The 'eGVHD App' could dramatically improve the quality of care and research as it increased the performance of the whole user group by about 30% at the first assessment and showed a trend for improvement of individual performance on repeated case evaluation.

PMID: 27042834 [PubMed - indexed for MEDLINE]



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Experimental investigation of the biomechanics of urethral tissues and structures.

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Experimental investigation of the biomechanics of urethral tissues and structures.

Exp Physiol. 2016 May 01;101(5):641-56

Authors: Natali AN, Carniel EL, Frigo A, Pavan PG, Todros S, Pachera P, Fontanella CG, Rubini A, Cavicchioli L, Avital Y, De Benedictis GM

Abstract
NEW FINDINGS: What is the central question of this study? Prostheses for treatment of urinary incontinence elicit complications associated with an inadequate mechanical action. This investigation aimed to define a procedure addressed to urethral mechanical characterization. Experimental tests are the basis for constitutive formulation, with a view to numerical modelling for investigation of the interaction between the tissues and a prosthesis. What is the main finding and its importance? Horse urethra, selected for its histomorphometric similarity to human urethra, was characterized by integrated histological analysis and mechanical tests on the biological tissue and structure, leading to constitutive formulation. A non-linear, anisotropic and time-dependent response was found, representing a valid basis for development of a numerical model to interpret the functional behaviour of the urethra. Urinary dysfunction can lead to incontinence, with an impact on the quality of life. Severe dysfunction can be overcome surgically by the use of an artificial urinary sphincter. Nonetheless, several complications may result from inappropriate functioning of the prosthesis, in many instances resulting from an unsuitable mechanical action of the device on the urethral tissues. Computational models allow investigation of the mechanical interaction between biological tissues and biomedical devices, representing a potential support for surgical practice and prosthesis design. The development of such computational tools requires experimental data on the mechanics of biological tissues and structures, which are rarely reported in the literature. The aim of this study was to provide a procedure for the mechanical characterization of urethral tissues and structures. The experimental protocol included the morphometric and histological analysis of urethral tissues, the mechanical characterization of the response of tissues to tensile and stress-relaxation tests and evaluation of the behaviour of urethral structures by inflation tests. Results from the preliminary experiments were processed, adopting specific model formulations, and also providing the definition of parameters that characterize the elastic and viscous behaviour of the tissues. Different experimental protocols, leading to a comprehensive set of experimental data, allow for a reciprocal assessment of reliability of the investigation approach.

PMID: 26864993 [PubMed - indexed for MEDLINE]



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The Moderating Role of Dysfunctional Parent-Child Relationships on the Association Between Outward Anger Expression and Physical Health in Youth From Low-Income Families.

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The Moderating Role of Dysfunctional Parent-Child Relationships on the Association Between Outward Anger Expression and Physical Health in Youth From Low-Income Families.

J Pediatr Health Care. 2016 Jul-Aug;30(4):366-73

Authors: Guenther KD, Van Dyk TR, Kidwell KM, Nelson TD

Abstract
OBJECTIVE: The purpose of this study is to examine the role of outward anger expression on physical health outcomes (number of illnesses in the past year, 2-year medical service utilization, and health-related quality of life) while also expanding on previous research by assessing the moderating effect of parent-child dysfunction.
METHOD: An ethnically diverse sample of 125 children, ages 8 to 11 years, was recruited from a family medicine practice serving a low-income population.
RESULTS: High levels of outward anger expression were related to a greater number of illnesses, greater medical service utilization, and lower health-related quality of life. Additionally, worse parent-child dysfunction exacerbated this relationship for a number of illnesses and medical service utilization.
CONCLUSION: Results suggest that health care providers should consider the influence of environmental and familial factors on the physical health of children with anger. Recommendations for identifying at-risk youth and improving anger expression as well as parent-child relationships are provided.

PMID: 26602110 [PubMed - indexed for MEDLINE]



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Predictors of Obstructive Sleep Apnea in Consecutive Patients with Metabolic Syndrome.

Predictors of Obstructive Sleep Apnea in Consecutive Patients with Metabolic Syndrome.

Metab Syndr Relat Disord. 2018 Jan 03;:

Authors: Pedrosa RP, Maki-Nunes C, Midlej-Brito T, Lopes HF, Freitas LS, Trombetta IC, Toschi-Dias E, Alves MJNN, Fraga RF, Rondon MU, Negrão CE, Bortolotto LA, Lorenzi-Filho G, Drager LF

Abstract
BACKGROUND: Recent evidence suggests that obstructive sleep apnea (OSA) is common in patients with metabolic syndrome (MetS) and may contribute to metabolic deregulation, inflammation, and atherosclerosis in these patients. In clinical practice, however, OSA is frequently underdiagnosed. We sought to investigate the clinical predictors of OSA in patients with MetS.
METHODS: We studied consecutive patients newly diagnosed with MetS (Adult Treatment Panel-III). All participants underwent clinical evaluation, standard polysomnography, and laboratory measurements. We performed a logistic regression model, including the following variables: gender, age >50 years, neck and waist circumferences, hypertension, diabetes, body mass index (BMI) >30 kg/m2, high risk for OSA by Berlin questionnaire, presence of excessive daytime somnolence (Epworth Sleepiness Scale), abnormal serum glucose, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.
RESULTS: We studied 197 patients (60% men; age: 49 ± 10 years; BMI: 32.9 ± 5.1 kg/m2). OSA (defined by an apnea-hypopnea index ≥15 events per hour) was diagnosed in 117 patients [59%; 95% confidence interval (CI): 52-66]. In multivariate analysis, male gender [odds ratio (OR): 3.28; 95% CI: 1.68-6.41; P < 0.01], abnormal glucose levels (OR: 3.01; 95% CI: 1.50-6.03; P < 0.01), excessive daytime sleepiness (OR: 2.38; 95% CI: 1.13-5.04; P = 0.02), and high risk for OSA by Berlin questionnaire (OR: 4.33; 95% CI: 2.06-9.11; P < 0.001) were independently associated with OSA.
CONCLUSIONS: Simple clinical and metabolic characteristics may help to improve the underdiagnosis of OSA in patients with MetS.

PMID: 29298404 [PubMed - as supplied by publisher]



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Exploring Opportunities for Primary Outpatient Palliative Care for Adults with Cystic Fibrosis: A Mixed-Methods Study of Patients' Needs.

Exploring Opportunities for Primary Outpatient Palliative Care for Adults with Cystic Fibrosis: A Mixed-Methods Study of Patients' Needs.

J Palliat Med. 2018 Jan 03;:

Authors: Hobler MR, Engelberg RA, Curtis JR, Ramos KJ, Zander MI, Howard SS, Goss CH, Aitken ML

Abstract
BACKGROUND: Persons with cystic fibrosis (CF) experience high morbidity and mortality, yet little is known about their palliative care needs and how clinicians may address these needs.
OBJECTIVES: (1) To identify palliative care and advance care planning needs of patients with CF and their families; and (2) to identify clinicians' potential roles in meeting these needs.
METHODS: A mixed-methods study of adult patients (age ≥18 years) with moderate-to-severe CF [forced expiratory volume in the first second (FEV1) <65% predicted] were recruited from a CF Center. Semi-structured interviews (30-60 minutes) and questionnaires were administered in person or by phone. Grounded theory was used to analyze the interviews. Questionnaires were analyzed descriptively.
RESULTS: Forty-nine patients (FEV1 % range = 19%-63%) participated; the participation rate was 80% for eligible patients. Three main domains of palliative care needs were identified: (1) to be listened to, feel heard, and be "seen"; (2) understanding the context around CF and its trajectory, with the goal of preparing for the future; and (3) information about, and potential solutions to, practical and current circumstances that cause stress. In questionnaires, few patients (4.3%) reported talking with their clinician about their wishes for care if they were to become sicker, but mixed-methods data demonstrated that more than half of participants were willing to receive palliative care services provided those services were adapted to CF.
CONCLUSION: Patients expressed a need for and openness to palliative care services, as well as some reluctance. They appreciated clinician communication that was open, forthcoming, and attuned to individualized concerns.

PMID: 29298400 [PubMed - as supplied by publisher]



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The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires' disease in humans.

The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires' disease in humans.

PLoS Pathog. 2018 Jan 03;14(1):e1006829

Authors: Ruiz-Moreno JS, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, Naujoks J, Sander LE, Witzenrath M, Cambier JC, Suttorp N, Schumann RR, Jin L, Hawn TR, Opitz B, CAPNETZ Study Group

Abstract
TRIAL REGISTRATION: ClinicalTrials.gov DRKS00005274, German Clinical Trials Register.

PMID: 29298342 [PubMed - as supplied by publisher]



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Neonicotinoid residues in UK honey despite European Union moratorium.

Neonicotinoid residues in UK honey despite European Union moratorium.

PLoS One. 2018;13(1):e0189681

Authors: Woodcock BA, Ridding L, Freeman SN, Pereira MG, Sleep D, Redhead J, Aston D, Carreck NL, Shore RF, Bullock JM, Heard MS, Pywell RF

Abstract
Due to concerns over negative impacts on insect pollinators, the European Union has implemented a moratorium on the use of three neonicotinoid pesticide seed dressings for mass-flowering crops. We assessed the effectiveness of this policy in reducing the exposure risk to honeybees by collecting 130 samples of honey from bee keepers across the UK before (2014: N = 21) and after the moratorium was in effect (2015: N = 109). Neonicotinoids were present in about half of the honey samples taken before the moratorium, and they were present in over a fifth of honey samples following the moratorium. Clothianidin was the most frequently detected neonicotinoid. Neonicotinoid concentrations declined from May to September in the year following the ban. However, the majority of post-moratorium neonicotinoid residues were from honey harvested early in the year, coinciding with oilseed rape flowering. Neonicotinoid concentrations were correlated with the area of oilseed rape surrounding the hive location. These results suggest mass flowering crops may contain neonicotinoid residues where they have been grown on soils contaminated by previously seed treated crops. This may include winter seed treatments applied to cereals that are currently exempt from EU restrictions. Although concentrations of neonicotinoids were low (<2.0 ng g-1), and posed no risk to human health, they may represent a continued risk to honeybees through long-term chronic exposure.

PMID: 29298300 [PubMed - in process]



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Seven days in medicine: 27 December 2017 to 2 January 2018

Public healthLocal Government Association attacks further cuts to public health fundingFurther government cuts to public health grants to local councils in England over the next two years have been...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=OgbK_eY_k70:7YtbuA8FjBk:V_sGLiP recent?d=qj6IDK7rITs recent?i=OgbK_eY_k70:7YtbuA8FjBk:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=OgbK_eY_k70:7YtbuA8FjBk:F7zBnMy recent?i=OgbK_eY_k70:7YtbuA8FjBk:-BTjWOF


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In clinical trial, cream reduces squamous cell carcinoma risk

New results from a clinical trial involving more than 900 military veterans at high risk for keratinocyte carcinoma skin cancer provides evidence that using the generic skin cream fluorouacil 5 percent for two to four weeks may reduce the risk of a...

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Tailoring cancer treatments to individual patients

Attempts to eradicate cancer are often compared to a "moonshot" -- the successful effort that sent the first astronauts to the moon. But imagine if, instead of Newton's second law of motion, which describes the relationship between an object's mass and...

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Infantile hemangiopericytoma leading to hypovolemic shock in a neonate



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The development of hypothalamic obesity in craniopharyngioma patients: A risk factor analysis in a well-defined cohort

Abstract

Background

Hypothalamic obesity (HO) is a major concern in patients treated for craniopharyngioma (CP). The influence of degree of resection on development of HO, event-free survival (EFS), and neuroendocrine sequelae is an issue of debate.

Procedure

A retrospective cohort consisting of all CP patients treated between 2002 and 2012 in two university hospitals was identified. Multivariable logistic regression was used to study the associations between preoperative BMI, age at diagnosis, tumor volume, performed surgical resection, and presence of HO at follow-up.

Results

Thirty-five patients (21 children and 14 adults) were included. Median follow-up time was 35.6 months (4.1–114.7). Four patients were obese at diagnosis. HO was present in 19 (54.3%) patients at last follow-up of whom eight were morbidly obese. Thirteen (37.1%) patients underwent partial resection (PR) and 22 (62.9%) gross total resection (GTR). GTR was related to HO (OR 9.19, 95% CI 1.43–59.01), but for morbid HO, obesity at diagnosis was the only risk factor (OR 12.92, 95% CI 1.05–158.73). EFS in patients after GTR was 86%, compared to 42% after PR (log-rank 9.2, P = 0.003). Adjuvant radiotherapy after PR improved EFS (log-rank 8.2, P = 0.004). Panhypopituitarism, present in 15 patients, was mainly seen after GTR.

Conclusions

HO is less frequent after PR than after GTR, but PR cannot always prevent the development of morbid obesity in patients with obesity at diagnosis. PR reduces the occurrence of panhypopituitarism. When developing a treatment algorithm, all these factors should be considered.



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Exercise program for children and adolescents with leukemia and lymphoma during treatment: A comprehensive review

Abstract

An exercise program (EP) during cancer treatment seems to be a valid strategy against physiological and quality-of-life impairments, but scientific evidence of benefits among pediatric patients is still limited. This review summarizes the literature focused on randomized controlled trials of EP offered to patients during leukemia and lymphoma treatment. Studies published up to June 2017 were selected from multiple databases and assessed by three independent reviewers for methodological validity. The review identified eight studies, but several types of bias have to be avoided to provide evidence-based recommendations accessible to patients, families, and professionals.



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A SVDD and -Means Based Early Warning Method for Dual-Rotor Equipment under Time-Varying Operating Conditions

Under frequently time-varying operating conditions, equipment with dual rotors like gas turbines is influenced by two rotors with different rotating speeds. Alarm methods of fixed threshold are unable to consider the influences of time-varying operating conditions. Hence, those methods are not suitable for monitoring dual-rotor equipment. An early warning method for dual-rotor equipment under time-varying operating conditions is proposed in this paper. The influences of time-varying rotating speeds of dual rotors on alarm thresholds have been considered. Firstly, the operating conditions are divided into several limited intervals according to rotating speeds of dual rotors. Secondly, the train data within each interval is processed by SVDD and the allowable ranges (i.e., the alarm threshold) of the vibration are determined. The alarm threshold of each interval of operating conditions is obtained. The alarm threshold can be expressed as a sphere, whose controlling parameters are the coordinate of the center and the radius. Then, the cluster center of the test data, whose alarm state is to be judged, can be extracted through -means. Finally, the alarm state can be obtained by comparing the cluster center with the corresponding sphere. Experiments are conducted to validate the proposed method.

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Cognate effects and cognitive control in patients with parallel and differential bilingual aphasia

Abstract

Background

Until today, there is no satisfying explanation for why one language may recover worse than another in differential bilingual aphasia. One potential explanation that has been largely unexplored is that differential aphasia is the consequence of a loss of language control rather than a loss of linguistic representations. Language control is part of a general control mechanism that also manages non-linguistic cognitive control. If this system is impaired, patients with differential aphasia could still show bilingual language activation, but they may be unable to manage activation in non-target languages, so that performance in another language is hindered.

Aims

To investigate whether a loss of cognitive control, rather than the loss of word representations in a particular language, might underlie differential aphasia symptoms.

Methods & Procedures

We compared the performance of seven bilinguals with differential and eight bilinguals with parallel aphasia with 19 control bilinguals in a lexical decision and a flanker task to assess bilingual language co-activation and non-linguistic control respectively.

Outcomes & Results

We found similar cognate effects in the three groups, indicating similar lexical processing across groups. Additionally, we found a larger non-linguistic control congruency effect only for the patients with differential aphasia.

Conclusions & Implications

The present data indicate preserved language co-activation for patients with parallel as well as differential aphasia. Furthermore, the results suggest a general cognitive control dysfunction, specifically for differential aphasia. Taken together, the results of the current study provide further support for the hypothesis of impaired cognitive control abilities in patients with differential aphasia, which has both theoretical and practical implications.



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Reducing task-based fMRI scanning time using simultaneous multislice echo planar imaging

Abstract

Purpose

To maintain alertness and to remain motionless during scanning represent a substantial challenge for patients/subjects involved in both clinical and research functional magnetic resonance imaging (fMRI) examinations. Therefore, availability and application of new data acquisition protocols allowing the shortening of scan time without compromising the data quality and statistical power are of major importance.

Methods

Higher order category-selective visual cortical areas were identified individually, and rapid event-related fMRI design was used to compare three different sampling rates (TR = 2000, 1000, and 410 ms, using state-of-the-art simultaneous multislice imaging) and four different scanning lengths to match the statistical power of the traditional scanning methods to high sampling-rate design.

Results

The results revealed that ~ 4 min of the scan time with 1 Hz (TR = 1000 ms) sampling rate and ~ 2 min scanning at ~ 2.5 Hz (TR = 410 ms) sampling rate provide similar localization sensitivity and selectivity to that obtained with 11-min session at conventional, 0.5 Hz (TR = 2000 ms) sampling rate.

Conclusion

Our findings suggest that task-based fMRI examination of clinical population prone to distress such as presurgical mapping experiments might substantially benefit from the reduced (20–40%) scanning time that can be achieved by the application of simultaneous multislice sequences.



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Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab

Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited, and prognosis is poor. Nivolumab (Opdivo) has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HNSCC who have disease progression on or after platinum-based therapy. Recently, in patients with metastatic malignant melanoma a significant improvement of outcome and response was achieved with the combination of ipilimumab (CTLA4 antibody) and the programmed death (PD)-1 inhibitor nivolumab compared with monotherapy. Based on these results, the combination of nivolumab and ipilimumab has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma. So far, there have been no data concerning the combination of nivolumab and ipilimumab in squamous cell head and neck cancer. We here present the case of a 46-year-old male with refractory squamous cell head and neck cancer, who was successfully treated with the PD-1 inhibitor nivolumab in combination with the anti-CTLA4 antibody ipilimumab.
Case Rep Oncol 2018;11:17–20

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A Patient with Advanced Gastric Cancer Who Achieved a Long-Term Prognosis by Early Diagnosis of Sister Mary Joseph’s Nodule

The patient was a 66-year-old woman. An induration of approximately 15 mm in size that accompanied redness was palpable in the umbilical fossa. She did not respond to 1-month antibiotic treatment provided by the previous physician. For this reason, a biopsy of the site was performed with the possibility of neoplastic disease in mind, resulting in the detection of adenocarcinoma. Subsequent detailed whole-body examination revealed advanced gastric cancer and peritoneal dissemination, and the induration in the umbilical fossa was diagnosed as a direct infiltration from the peritoneal dissemination. Metastasis or infiltration of malignant tumor to the umbilicus is called Sister Mary Joseph’s nodule (SMJN), and considered as a sign of poor prognosis. However, this case was successfully treated and achieved a long-term prognosis by the early diagnosis of SMJN. In routine clinical practice, it is considered necessary to examine patients carefully, as not to overlook SMJN.
Case Rep Oncol 2018;11:11–16

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Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod

Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.
Case Rep Oncol 2018;11:1–5

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Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment

Introduction: Nivolumab is a promising treatment in patients with advanced malignancies. Among immune-related adverse events, autoimmune thyroid disorders are frequently reported. Patient: A 61-year-old male patient had no history of familial or personal thyroid disease. In 2012, this patient, a heavy smoker, presented with non-small-cell lung cancer that was treated with radiotherapy and chemotherapy. In 2015, the cancer progressed with cervical compressive symptoms, and the patient was treated with nivolumab. Results: After 3 infusions, bilateral eyelid ptosis and bilateral conjunctival redness with chemosis were observed. Ophthalmologic examination revealed severe proptosis with complete ophthalmoplegia but with normal vision, color test, and optic disk. Thyroid function tests were normal (TSH = 0.65 mU/L, free T4 = 15.4 pmol/L) without anti-thyroperoxidase or anti-TSH receptor antibodies. CT scan of the orbits confirmed marked bilateral proptosis with expansion of the orbital adipose tissue without significant thickening of extraocular muscles. T2-weighted MRI showed inflammation of orbital adipose tissue. Nivolumab treatment was withdrawn, and the patient received weekly intravenous high-dose methylprednisolone (1 g for 2 weeks, 500 mg for 4 weeks, and 250 mg for 5 weeks). After the first 3 cycles, significant improvement of left chemosis was observed whereas bilateral ptosis and ophthalmoplegia were unchanged. The patient was euthyroid without thyroid autoimmunity 1 week prior to his death due to massive hemoptysis. Conclusion: We report severe inflammatory ophthalmopathy in a euthyroid patient with non-small-cell lung cancer during nivolumab therapy. The occurrence of such ophthalmic adverse events is likely to increase during nivolumab therapy in patients with advanced malignancies.
Eur Thyroid J

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Genes, Vol. 9, Pages 14: Surveillance of Foodborne Pathogens: Towards Diagnostic Metagenomics of Fecal Samples

Genes, Vol. 9, Pages 14: Surveillance of Foodborne Pathogens: Towards Diagnostic Metagenomics of Fecal Samples

Genes doi: 10.3390/genes9010014

Authors: Sandra Andersen Jeffrey Hoorfar

Diagnostic metagenomics is a rapidly evolving laboratory tool for culture-independent tracing of foodborne pathogens. The method has the potential to become a generic platform for detection of most pathogens and many sample types. Today, however, it is still at an early and experimental stage. Studies show that metagenomic methods, from sample storage and DNA extraction to library preparation and shotgun sequencing, have a great influence on data output. To construct protocols that extract the complete metagenome but with minimal bias is an ongoing challenge. Many different software strategies for data analysis are being developed, and several studies applying diagnostic metagenomics to human clinical samples have been published, detecting, and sometimes, typing bacterial infections. It is possible to obtain a draft genome of the pathogen and to develop methods that can theoretically be applied in real-time. Finally, diagnostic metagenomics can theoretically be better geared than conventional methods to detect co-infections. The present review focuses on the current state of test development, as well as practical implementation of diagnostic metagenomics to trace foodborne bacterial infections in fecal samples from animals and humans.



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Utility of polypropylene templates for delayed delimitation of margins from ill-defined tumors



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Darier disease-like hyperkeratotic papules and invasive squamous cell carcinoma in a patient with melanoma treated with dabrafenib



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Skin and coeliac disease, a lot to think about: a case series

Coeliac disease (CD) is an autoimmune disease, characterised by a permanent sensitivity to gluten. It is being progressively recognised as a multisystemic disease, with multiple extraintestinal manifestations. Skin conditions (eg, dermatitis herpetiformis) are an example of its manifestations; however, its underlying mechanisms are still not well understood. This article presents three cases of uncommon skin conditions in patients with a history of CD. Two of them concern linear IgA bullous dermatosis and erythema nodosum, which have been described in the literature as having potential associations with CD, though only a few cases were reported. The third case corresponds to pityriasis lichenoides–a rare lymphoproliferative disorder of unknown aetiology–, which has no correlation with CD in the literature reviewed. The authors aim to draw attention to the possibility of CD as a potential predisposing factor for the occurrence of these skin diseases.



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Recurrent hospitalisations in a rare case of hemicorporectomy: a challenging case for medical management

Hemicorporectomy, or translumbar amputation, is a radical surgery involving the dissection of the body at the waist and is usually reserved for complex medical conditions including locally invasive malignancy and terminal pelvic osteomyelitis. Only 71 cases have previously been reported. We present a rare case of hemicorporectomy in a 53-year-old patient with terminal pelvic osteomyelitis which occurred after he suffered a gunshot wound at T6 causing paraplegia at the age of 31. Unfortunately, this patient continued to suffer recurrent hospitalisations and sepsis events secondary to chronic, non-healing advanced pressure ulcers and complicated urinary tract infections despite repeated courses of broad-spectrum intravenous antibiotics and surgical debridements. In light of his diminished quality of life and poor prognosis, the patient’s family chose to manage his condition conservatively with home hospice. This case illustrates the significant challenges in the medical and surgical management of hemicorporectomy patients.



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Recurrent cytomegalovirus colitis: a rare case of immune reconstitution inflammatory syndrome

Cytomegalovirus (CMV) colitis usually occurs in patients with advanced immunosuppression when the CD4 count is <50 cells/μL. We reported a case of recurrent CMV colitis in a patient with HIV who presented with profuse lower gastrointestinal bleed. This was a case of immune reconstitution inflammatory syndrome (IRIS) manifesting as CMV colitis and has been reported only once in the literature previously. This patient had a CD4 count of 157 cells/μL and undetectable viral load after being on antiretroviral therapy (ART) for 5 months, which was consistent with IRIS. The diagnosis of CMV was confirmed by a colonoscopy and a biopsy. This case highlights the fact that CMV colitis can manifest despite a moderately preserved CD4 count and the clinicians must have a high index suspicion for IRIS syndrome especially when someone was recently started on ART. Since effective treatment is available, it is important not to miss the diagnosis of CMV colitis.



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Syphilitic jaundice: a rare manifestation of the secondary stage presenting a missed opportunity to prevent ocular syphilis

The classical presentation of secondary syphilis comprises skin rashes, mucosal ulceration and lymphadenopathy. However, this disseminated stage can also present with symptoms and signs of ocular, neurological, pulmonary, renal, musculoskeletal and digestive tract disease. We report the case of a gay man who presented with icteric hepatitis. Although he underwent an exhaustive series of investigations (some of which were invasive), syphilis was not initially considered in the differential diagnosis. His jaundice resolved spontaneously, but he subsequently developed an acute optic neuritis. Early syphilis is relatively common in men who have sex with men (MSM). Prompt diagnosis and treatment in this case would have prevented ocular involvement. Syphilis testing should be considered in all MSM presenting with unexplained symptoms and signs.



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Bilateral Motor Cortex Control for Left Thumb Movement: An Incidental Finding Through Functional MRI (fMRI)

We report a case of a healthy, right-hand dominant young male who was a volunteer for a pilot run of a functional MRI (fMRI) study. The fMRI was performed with a 3.0 Tesla MRI scanner using a finger tapping task-based activity. The subjects were instructed to perform flexion of the right thumb and left thumb consecutively (activation task) and neuronal activation in bilateral primary motor cortex (PMC) were observed during each task. One particular subject demonstrated bilateral PMC activation during the left-thumb movement task, instead of the expected activation of the contralateral PMC alone.



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Inherited haemochromatosis with C282Y mutation in a patient with alpha-thalassaemia: a treatment dilemma

A Caucasian 24-year-old female patient suffers from two hereditary disorders: alpha-thalassaemia, which is prevalent in Asia and rare in Europe, and haemochromatosis, which is prevalent among northern Europe and rare in Asia. The clinical presentation and management of one of these diseases is controversial for the other. She presented 5 years ago with a clinical picture of refractory iron-deficiency anaemia secondary to menorrhagia. On treating her with the standard iron therapy, her anaemia persists although with adquate iron stores. This prompted further investigations that revealed in addition to hereditary haemochromatosis, alpha-thalassaemia because of abnormal blood indices. The treatment of thalassaemia with either iron or blood transfusion is not advisable in haemochromatosis, while standard treatment of haemochromatosis with venesection will worsen the anaemia. As iron chelating agents were not approved in Australia for haemochromatosis, haematinics support was commenced with a satisfactory improvement of anaemia thus allowing for further venesection.



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Management of a 15-year-old scaphoid non-union

Scaphoid non-union affects wrist joint function and is often associated with a predictable pattern of degenerative change. A 30-year-old man presented with a symptomatic 15-year-old right scaphoid fracture with secondary scaphoid non-union advanced collapse of his right wrist. There was no evidence of avascular necrosis. The initial injury was from a fall onto his outstretched hand. We performed a right scaphoid open reduction, internal fixation and iliac crest bone graft. One year after the operation, the patient had good wrist function and grip strength. A CT scan showed union of the fracture. Studies have shown that if the time between initial fracture and treatment of non-union exceeds 5 years, the chances of healing of the non-union are markedly reduced. In our case, despite the long duration between timing of injury and surgery, there was union and good return of function.



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Saphenous vein graft aneurysm and fistula with compression mimicking mitral stenosis

We present the case of a patient who presented with acute coronary syndrome and was found to have a mass compressing the left atrium. An angiogram revealed a large saphenous vein graft aneurysm with a fistula into a cardiac chamber, presumed to be the left ventricle. The patient also developed a functional mitral stenosis secondary to this mass causing left atrial compression. The patient passed away prior to receiving surgery. We describe a rare case of venous graft aneurysm with compression and fistula to a chamber other than the right atrium, that to our knowledge has yet to be reported.



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Enhanced elimination of cyclophosphamide by high cut-off haemodialysis: single-dose pharmacokinetics in a patient with cast nephropathy

High cut-off (HCO) haemodialysis removes free light chains in patients with multiple myeloma. This is possible as HCO dialysers allow clearance of molecules up to a molecular weight of 65 kDa. In contrast, high-flux dialysers, which are used in routine haemodialysis, only remove molecules up to a molecular weight of 20 kDa. Even though patients with advanced myeloma frequently need dialysis and alkylating agents, drug dosing recommendations in this patient population are scarce at best or absent as for cyclophosphamide dosing in patients with myeloma undergoing HCO dialysis. Therefore, we aimed to determine pharmacokinetics of cyclophosphamide in a 52-year-old man (height 172 cm, weight 80 kg) with cast nephropathy. Intermittent 4-hour haemodialysis was started ~6 hours after the end of a 70 min cyclophosphamide infusion containing 1700 mg of this drug. Blood/dialysate flow rates were 300/500 mL/hour, respectively. Peak concentration of cyclophosphamide was 24.7 mg/L. Using HCO dialysis, plasma concentration of cyclophosphamide decreased from 10.8 mg/L to 3.7 mg/L during the treatment. The calculated whole blood dialyser clearance was 166 mL/min. HCO dialysis led to a marked decrease of cyclophosphamide resulting in a a 50% reduction in half-life as compared with the half-life before dialysis. This removal has to be accounted for in dosing cyclophosphamide.



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Extramedullary plasmacytoma: rare neoplasm of parotid gland

A 45-year-old man presented with left-sided facial swelling. Initial excisional biopsy was done somewhere else without prior imaging and it came out to be pleomorphic adenoma; local imaging after biopsy showed mass over the left parotid gland with ipsilateral lymphadenopathy. On examination, there was a well-circumscribed mass with signs of left facial nerve palsy. He underwent left radical parotidectomy with ipsilateral modified radical neck dissection, and per operatively, it came out to be neoplastic lesion. Final histopathology was plasma cell neoplasm of the parotid gland. After surgery, the patient received radiation therapy to the left parotid region on account of uncertain surgical margins. It has been 3 years down the road that there is no evidence of local recurrence or transformation into multiple myeloma. Available evidence reveals that mere surgery for extramedullary plasmacytoma is not enough for local control whenever there is doubt of residual disease consider radiation therapy.



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Posterior reversible encephalopathy syndrome in an HIV-infected patient on antiretroviral treatment: what is the risk factor?

Posterior reversible encephalopathy syndrome (PRES) is a rare but well-described syndrome associated with a high morbidity and a substantial mortality. We present an illustrative case of an HIV-infected but virologically suppressed patient who complained of visual impairment accompanied by severe headache and epileptic seizures. The cerebral CT scan and the follow-up cranial MRI confirmed the diagnosis of PRES. Unlike the cases of HIV-infected patients with PRES published so far, our patient suffered neither from advanced immunodeficiency nor from opportunistic infection or from any other evident predisposing factor. This case highlights that the absence of classical risk factors does not exclude the diagnosis of PRES. We discuss the hypothesis that in accordance with the new pathophysiological theory, persistent HIV-associated cerebrovascular reactivity in combination with endothelial dysfunction may represent an undetected risk factor for the development of PRES in virologically and immunologically stable patients.



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Block vertebra

We report a case of congenital kyphosis in a 5-year-old child. Although she was presented before the age of 1 year to her local orthopaedic unit, a definitive diagnosis of unsegmented vertebra was made when she was referred to our unit. The child was treated with posterior fusion, which improved part of the deformity and completely prevented progression. We discuss the case and the condition, which if ignored can lead to progressive painful deformity and paralysis.



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Catamenial anaphylaxis: a woman under monthly progesterone curse

Catamenial or cyclical anaphylaxis is a complex clinical syndrome with poorly reported incidence and prevalence in the literature review. The underlying mechanism is still a myth although a few proposed hypotheses are stated. Early recognition of these symptoms will bring optimal treatment and prevent unnecessary intubation and complications. Here, we present a 48-year-old woman without significant medical and family history with recurrent angioedema in the setting of catamenial anaphylaxis or cyclical anaphylaxis in the setting of progesterone hypersensitivity.



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Acute alveolar haemorrhage in hepatitis C-related cryoglobulinaemic vasculitis

We describe a patient with untreated hepatitis C virus (HCV) infection presenting with pulmonary renal syndrome. He rapidly developed bilateral lung infiltrates and respiratory failure, and bronchoscopy confirmed acute alveolar haemorrhage secondary to cryoglobulinaemic vasculitis. Early bronchoscopy to confirm the diagnosis and consequent institution of immunosuppressive therapy led to excellent outcomes, which otherwise is reported in the literature to carry significant mortality. Therefore, in patients with HCV presenting with bilateral lung infiltrates, physicians must maintain a high degree of clinical suspicion for alveolar haemorrhage secondary to cryoglobulinaemic vasculitis.



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Clinically amyopathic dermatomyositis associated with anti-MDA5 antibody

Clinically amyopathic dermatomyositis (CADM) is a rare entity that presents with cutaneous manifestations of classic dermatomyositis but without muscle weakness or abnormal muscle enzymes. It is more common in young white and Asian females. A subset of patients with CADM has a specific antibody known as anti-MDA5. These patients have a more aggressive course with distinct cutaneous features, pulmonary involvement and early death. Here, we present the case of a 64-year-old Caucasian male with no significant medical history who was admitted with marked weight loss and a painful rash for 6 months. Patient had no muscle weakness and his rash was characteristic of classic dermatomyositis. Skin biopsy was suggestive of dermatomyositis but muscle enzymes were normal. His serum was positive for anti-MDA5 antibody. Extensive workup failed to detect any malignancy but he did show non-specific interstitial pneumonia. He was treated with prednisone and mycophenolate with good clinical response.



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Invasive papillary breast cancer with Pagets disease: first reported association and literature review

Invasive papillary carcinoma of the breast and Paget’s disease are both rare entities. We report the first known case of invasive papillary carcinoma associated with Paget’s disease in a woman who presented clinically with a nipple mass. While invasive papillary carcinoma has been reported to have an indolent course without need for overtreatment, our patient had unusual unfavourable histological features. Literature review of this rare subtype was performed.



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Unusual trifurcation of a single left coronary artery

Congenital coronary artery anomalies are rare and usually an incidental finding during coronary angiography. Most of the anomalies are benign in nature; however, some are malignant and may result in sudden cardiac death. A 46-year-old woman with diabetes and hypertension underwent coronary angiography for evaluation of exertional angina, which revealed an unusual trifurcation of a single left coronary artery with an anomalous origin of the right coronary artery from the left anterior descending artery but no significant coronary narrowing. The patient was managed conservatively.



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Incidental discovery of a new and clinically important anatomic variant of the internal thoracic artery in a young male trauma patient

The internal thoracic artery (ITA) is the largest thoracic wall artery and is clinically important primarily for use in coronary artery bypass grafting. A number of anatomic variants of the ITA have been reported; however, bilateral, aberrant lateral branches of the ITA never have. The importance of this finding lies in the positioning of the artery at a potential chest tube insertion site. Here, we report the identification, on CT scan, of this rare variation in a young male trauma patient.



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Paratesticular myositis ossificans of the spermatic cord

A 56-year-old man presented with a painless scrotal lump, enlarging over the preceding 1 month. The lump was roughly 1 cm in size, and located in his left hemiscrotum and separate from the testis. An ultrasound revealed an echogenic focus with dystrophic tissue calcification. Subsequent surgical excision and histopathological analysis revealed it to be late-stage myositis ossificans, a benign, extraosseous formation of the bone or cartilage. We report of only the second described case of myositis ossificans of the spermatic cord in the literature to date.



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Unilateral orbital fat change

A man in his 60s suffering from open-angle glaucoma attended a routine glaucoma follow-up complaining that his left eye has changed in appearance. On examination, there was extensive loss of orbital fat giving the appearance of a sunken in globe. A diagnosis of prostaglandin-associated periorbitopathy was made as the man had been taking a prostaglandin analogue for his glaucoma for over 4 years in his left eye only.



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IJERPH, Vol. 15, Pages 68: Self-Medication Practice and Associated Factors among Residents in Wuhan, China

IJERPH, Vol. 15, Pages 68: Self-Medication Practice and Associated Factors among Residents in Wuhan, China

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15010068

Authors: Xiaosheng Lei Heng Jiang Chaojie Liu Adamm Ferrier Janette Mugavin

Background: This study aims to examine the prevalence and predictors associated with self-medication, and related consequences in Wuhan, China. Methods: Two-hundred-sixty residents were interviewed from randomly selected four districts of Wuhan, China. A modified version of Anderson’s health behavioral model was used in the survey to collect information of self-medication behavior. Multivariable logistic regression analyses were used to measure correlates of the prevalence of self-medication. Results: Nearly half of the respondents would select self-medication, and 39.1% would see a doctor if they felt sick. The most common self-medicated illnesses were cold and cough, cardiovascular disease and gastrointestinal disease. The main reasons for self-medication were that the illness was not severe (enough) to see the doctor (45%); the patient did not think that the trouble of seeing a doctor was worth the effort (23%); the patient had no time to see the doctor (12%), and the patient did not want to pay high medical costs (15%). Logistic regression results suggested that respondents tended to select self-medication if the illness was minor or short-term (less than seven days). Conclusions: Our findings suggest that more strict regulation on over-the-counter medicines may be required to reduce health risks related to self-medication. Targeted health education on the risks of self-medication should be considered.



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Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival

Abstract

Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR-related genes) in CM-specific survival (CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of 191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS. Using multivariate Cox proportional hazards regression analysis, we identified three independent SNPs (RORA rs782917 G>A, RORA rs17204952 C>T and DNMT1 rs7253062 G>A) as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) and 95% confidence interval of 1.62 (1.25-2.09), 1.60 (1.20-2.13) and 1.52 (1.20-1.94), respectively. Combined analysis of risk genotypes of these three SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (Ptrend < 0.001); however, no improvement in the prediction model was observed (area under the curve [AUC] = 79.6% to 80.8%, P = 0.656), when these risk genotypes were added to the model containing clinical variables. Our findings suggest that genetic variants of RORA and DNMT1 may be promising biomarkers for CMSS, but these results needed to be validated in future larger studies. This article is protected by copyright. All rights reserved.



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Atopic allergic conditions and pancreatic cancer risk: Results from the Multiethnic Cohort Study

Abstract

Previous case-control studies have suggested that atopic allergic conditions (AACs) are inversely associated with pancreatic cancer, but this relationship has not been supported in many prospective settings. In this study, we investigated the influence of AACs (asthma, hay fever, or allergy) and the treatment of these conditions on pancreatic cancer risk among participants of the Multiethnic Cohort Study (MEC). AACs and antihistamine use were assessed via a baseline questionnaire when participants joined the MEC in 1993-1996. Risk ratios (RRs) and 95% confidence intervals (CIs) for pancreatic cancer incidence by AACs and antihistamines were calculated using Cox regression, adjusting for age, sex, ethnicity, education, smoking status, family history of pancreatic cancer, body mass index, diabetes, and alcohol intake. We further evaluated associations among subgroups defined by age, sex, ethnicity, follow-up time and known pancreatic cancer risk factors. During an average 16-year follow-up, 1,455 incident cases of pancreatic cancer were identified among 187,226 white, African American, Latino, Japanese American and Native Hawaiian men and women. AACs (RR 1.00, 95% CI 0.88-1.12) and antihistamines (RR 0.92, 95% CI 0.78-1.07) were not clearly associated with pancreatic cancer incidence. While these associations were also null for most subgroups, we did observe protective associations of AACs (RR 0.74, 95% CI 0.56-0.98) and antihistamines (RR 0.66, 95% CI 0.45-0.96) among the oldest participants (70+). Our results, in agreement with past prospective studies, suggest that AACs are not associated with pancreatic cancer in general, but the observed protective associations among the oldest age group may warrant future investigation. This article is protected by copyright. All rights reserved.



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In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro

Abstract

Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for seven days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8+ T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8+ T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8+ T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L, and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8+ T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo. This article is protected by copyright. All rights reserved.



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Mouse model of post-surgical primary tumor recurrence and regional lymph node metastasis progression in HPV-related head and neck cancer

Abstract

HPV-positive head and neck squamous cell carcinoma (HNSCC) is increasingly frequent. Management is particularly debated in the case of post-surgical high-risk features, i.e., positive surgical margins and extracapsular spread (ECS). In this increasingly complex emerging framework of HNSCC treatment, representative pre-clinical models are needed to support future clinical trials and advances in personalized medicine. Here, we present an immunocompetent mouse model based on the implantation of mouse tonsil epithelial HPV16-E6/E7-expressing cancer cells into the submental region of the floor-of-the-mouth. Primary tumors were found to replicate the patterns of human HNSCC local invasion and lymphatic dissemination. To study disease progression after surgery, tumors were removed with residual disease. Surgical resection of tumors was followed by a high rate of local recurrences (>90%) within the first 2 to 3 weeks. While only 50% of mice had lymph node metastases (LNM) at time of primary tumor excision, all mice with recurrent tumors showed evidence of LNM. To study the consecutive steps of LNM progression and distant metastasis development, LNs from tumor-bearing mice were transplanted into naïve recipient mice. Using this approach, transplanted LNs were found to recapitulate all stages and relevant histological features of regional metastasis progression, including ECS and metastatic spread to the lungs. Altogether, we have developed an immunocompetent HPV-positive HNSCC mouse model of post-surgical local recurrence and regional and distant metastasis progression suitable for pre-clinical studies. This article is protected by copyright. All rights reserved.



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The Anti-Inflammatory Effect of Fructus Kochiae on Allergic Contact Dermatitis Rats via pERK1/2/TLR4/NF-κB Pathway Activation

Allergic contact dermatitis (ACD) is a common irritability skin disease, which can be cured by using the Chinese patent medicine. To explore the pharmacological effect of total flavonoids of Fructus Kochiae (FK) on ACD, we used dinitrochlorobenzene- (DNCB-) induced ACD rats. Five groups were used in our experiments. The normal group and the DNCB group were treated with 0.5% CMC-Na; the DNCB + hFK group was treated with a high dose of total flavonoids of FK (200 mg/kg); the DNCB + lFK group was treated with a low dose of FK (100 mg/kg); the DNCB + Pre group was treated with prednisolone acetate (2.5 mg/kg). The results showed that FK treatment had significantly attenuated the inflammation induced by DNCB. The increased concentration of cytokines including IL-6, IL-18, and IFN-γ in ACD rats could be reversed by the FK administration, while IL-10 expressed the opposite result; the expression level of TLR4, pERK1/2, and NF-κB could be downregulated by the treatment with FK in the ACD rat. In a word, the total flavonoids of the FK had an anti-inflammatory effect on the DNCB-induced ACD rat; this regulatory mechanism was highly possible based on the pERK1/2/TLR4-NF-κB pathway activation.

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Acute Primary Adrenal Insufficiency after Hip Replacement in a Patient with Acute Intermittent Porphyria

Adrenal insufficiency is a potentially life-threatening condition when it occurs acutely, as in adrenal hemorrhage. Generally it is not reversible and requires chronic replacement therapy. Acute intermittent porphyria (AIP) is a rare genetic disease characterized by alterations in heme biosynthesis that result in accumulation of precursors in tissues. A crisis can be triggered by many conditions such as surgery and infections. Symptoms are similar to those of acute hypoadrenalism. Moreover, both conditions are characterized by hyponatremia. We describe the case of a postmenopausal woman known to be affected by AIP who developed after surgery a primary adrenal insufficiency associated with adrenal enlargement; the latter completely reverted in six months.

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An Annotated List of Auchenorrhyncha and Heteroptera Collected in the Coastal Salt Marshes of the Mississippi Delta in Louisiana

Insects that live in the saltwater and brackish marshes, which fringe the northern coast of the Gulf of Mexico, are largely unstudied. During 2011–2013, a survey of insect fauna of the coastal salt marshes of the Mississippi Delta in Louisiana was conducted. We present the species of terrestrial representatives of Heteroptera and Auchenorrhyncha collected during that study. The Auchenorrhyncha are represented by 33 species in 6 families, with Cicadellidae (16 species) and Delphacidae (13 spp.), and are the most diverse. The terrestrial heteropterans are represented by 11 species in 5 families with the majority of species in Miridae (6 spp.). A list of species, annotated with numbers of specimens collected, ranges of collection dates (seasonality), and published information on their hosts, habitats, and ranges, is presented. Of 44 identified species, ten species (22.7%) are reported from Louisiana for the first time. The paper provides evidence of a diverse terrestrial arthropod community in brackish marshes; a community that is largely understudied.

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Meta-analysis of voxel-based morphometry studies of gray matter abnormalities in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis

Abstract

We aimed to perform a meta-analysis to systematically determine the most consistent regions of gray matter volume (GMV) abnormality in patients of unilateral mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), and to reveal the difference of GMV abnormality between the patients with left-sided and right-sided MTLE-HS. A comprehensive and systematic search was performed in PubMed for voxel-based morphometry (VBM) studies of MTLE-HS. A total of 12 MTLE-HS studies, including 9 left-sided MTLE-HS (LMTLE-HS) and 8 right-sided MTLE-HS (RMTLE-HS) studies were included. The activation likelihood estimation (ALE) method was applied in our meta-analysis. Compared to the healthy controls, MTLE-HS patients showed significant GMV decrease in the parahippocampal gyrus, left pulvinar and right pyramis. For LMTLE-HS, the most consistent GMV decrease was detected in the left parahippocampal gyrus. For RMTLE-HS, the most consistent GMV decrease was found in the right parahippocampal gyrus. No shared regions of significant GMV reduction were found between LMTLE-HS and RMTLE-HS either. This meta-analysis revealed that MTLE-HS patients had significant GMV reduction even beyond the hippocampus, and the subtypes showed distinct reduction patterns. Our findings, if were further verified with larger samples, would have implications for the clinical diagnosis of MTLE-HS.



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Dose and schedule modification are required for long-term continuation of sunitinib in Japanese patients with advanced pancreatic neuroendocrine tumors

Abstract

Purpose

This study aimed to clarify the efficacy and safety of sunitinib in Japanese patients with pancreatic neuroendocrine tumors (PNET), especially by focusing on dose and schedule modification.

Methods

Sixteen patients with advanced PNET treated with sunitinib were reviewed retrospectively. Efficacy was evaluated by progression-free survival (PFS) and objective tumor response. Toxicity profile was assessed regularly. Correlation between relative dose intensity (RDI) and treatment period was also evaluated.

Results

The median PFS was 25.8 months, and the probability of PFS at 1-year was 92%. The objective response rate and clinical benefit rate were 44% and 69%, respectively. The common adverse drug reactions (ADRs) were hand-foot syndrome (88%), neutropenia (75%), leucopenia (75%), and diarrhea (63%). Due to the development of severe ADRs, 81% required dose reduction and 31% discontinued sunitinib treatment, respectively. Prolonged treatment period was significantly correlated with decreased RDI (Spearman r = − 0.57, P = 0.022). The median RDI among 9 patients whom continued sunitinib more than 1 year was 49%.

Conclusions

Sunitinib showed significant clinical benefit in Japanese patients with advanced PNET in the real-world clinical setting. Successful management of ADRs with appropriate dose reduction and interruption can enable long-term continuation of sunitinib.



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Persistent cytarabine and daunorubicin exposure after administration of novel liposomal formulation CPX-351: population pharmacokinetic assessment

Abstract

Purpose

CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML). The current study investigated the pharmacokinetics (PK) of this liposomal formulation.

Methods

CPX-351 PK data (cytarabine, daunorubicin, and metabolites) from a phase I study of relapsed and refractory AML were used for the analysis. Therapy was given days 1, 3, and 5 of induction (3–134 units/m2). We developed a population PK model to characterize CPX-351 disposition.

Results

39 patients (3589 samples) were evaluated. Liposomal cytarabine and daunorubicin were modeled separately with their respective metabolites. A one-compartment model fit the parent compounds well; the metabolites required two-compartment models. Weight was an independent predictor of liposomal volumes; mild renal and liver dysfunction were not predictors of clearance or volume (maximum creatinine 1.6 mg/dL and total bilirubin 1.8 mg/dL). Liposomal clearances of the two drugs were highly correlated and 1000-fold smaller than published non-encapsulated values supporting prolonged encapsulation in the liposome.

Conclusions

The PK model demonstrates prolonged exposure to cytarabine and daunorubicin without increases in non-hematologic toxicity that indicates retention of the drugs within the liposome. The unique pharmacology of this formulation may allow for simplified regimens and improved outcomes.



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Correction to: Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14 C-microtracer and therapeutic dose in cancer patients

Abstract

The article ‘‘Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients’’, written by L. van Andel, H. Rosing, Z. Zhang, L. Hughes, V. Kansra, M. Sanghvi, M. M. Tibben, A. Gebretensae, J. H. M. Schellens and J. H. Beijnen, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 17th October 2017 without open access.



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Pharmacokinetics and safety of panitumumab in a patient with chronic kidney disease

Abstract

Purpose

Data on panitumumab dosing in cancer patients with renal insufficiency are lacking. Here, we report a 63-year-old metastatic colorectal cancer patient with chronic kidney injury with a glomerular filtration rate of approximately 11 mL/min.

Methods

Pharmacokinetic parameters, including dose-normalized area under the curve, clearance and elimination half-life (T 1/2) after the 11th and 12th infusions were estimated using trapezoidal non-compartmental methods. Data were compared to previous reported pharmacokinetic data from studies in patients with normal renal function.

Results

The results show that the pharmacokinetic data in this patient with kidney failure are comparable to those in patients with adequate renal function. Moreover the treatment was well tolerated in this patient.

Conclusion

This study suggests that panitumumab can be safely used in cancer patients with renal impairment without dose adjustment.



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