Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Σάββατο 26 Αυγούστου 2017

Flavoprotein fluorescence imaging-based electrode implantation for subfield-targeted chronic recording in the mouse auditory cortex

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Publication date: Available online 26 August 2017
Source:Journal of Neuroscience Methods
Author(s): Jun Nishikawa, Yuto Ohtaka, Yuishi Tachibana, Yasutaka Yanagawa, Hisayuki Osanai, Takeaki Haga, Takashi Tateno
BackgroundChronic neural recording in freely moving animals is important for understanding neural activities of cortical neurons associated with various behavioral contexts. In small animals such as mice, it has been difficult to implant recording electrodes into exact locations according to stereotactic coordinates, skull geometry, or the shape of blood vessels. The main reason for this difficulty is large individual differences in the exact location of the targeted brain area.New methodsWe propose a new electrode implantation procedure that is combined with transcranial flavoprotein fluorescence imaging. We demonstrate the effectiveness of this method in the auditory cortex (AC) of mice.Results: Prior to electrode implantation, we executed transcranial flavoprotein fluorescence imaging in anesthetized mice and identified the exact location of AC subfields through the skull in each animal. Next, we surgically implanted a microdrive with a tungsten electrode into exactly the identified location. Finally, we recorded neural activity in freely moving conditions and evaluated the success rate of recording auditory responses.Comparison with existing method(s)These procedures dramatically improved the success rate of recording auditory responses from 21.1% without imaging to 100.0% with imaging. We also identified large individual differences in positional relationships between sound-driven response areas and the squamosal suture or blood vessels.ConclusionsCombining chronic electrophysiology with transcranial flavoprotein fluorescence imaging before implantation enables the realization of reliable subfield-targeted neural recording from freely moving small animals.



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State of knowledge of research in the Guinean forests of West Africa region

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Publication date: Available online 26 August 2017
Source:Acta Oecologica
Author(s): Luca Luiselli, Daniele Dendi, Edem A. Eniang, Barineme B. Fakae, Godfrey C. Akani, John E. Fa
The Guinean forests of West Africa (GFWA) region is of highest conservation value in Africa and worldwide. The aims of this review are to systematically identify and collate studies focusing on the environment in the region. We found that, after Google Scholar search, in over 112,000 results for 17 disciplines, three countries (Nigeria, Cameroon and Togo) were subjected to much more investigations than the other countries. Guinea, Liberia, and Sierra Leone were the least studied countries, and overall there was a significant West to East increasing trend for all seven considered disciplines (Ecology, Zoology, Botany, Conservation biology, Pollution, Climate change and Ecological economy) in terms of number of results. Within 'Ecology' 'macroecology and biodiversity' was the most studied subdiscipline. Baseline taxonomic studies in 'Zoology' and 'Botany' received little interest, particularly in 2006–2016. For 'Conservation biology', studies focusing on 'protected areas' were more numerous than for any other subsector, followed by 'biodiversity surveys'. Our analysis revealed that there were significantly more studies focusing on forests than on mangrove areas. Our results pointed out that, there is an urgent need for more rigorous taxonomical and fine-scale distribution studies of organisms across the whole region, not only for the traditionally overlooked groups (e.g. invertebrates). It is also stressed that studies of macropatterns in conservation biology research for the region should be performed by more reliable data at the more local scale, given the misuse that has been done by general studies of these limited/biased data for inferring patterns. Long-term longitudinal studies on biodiversity patterns of important forest sites and population biology of selected populations are urgently needed, as these have been almost entirely neglected to date. Crucial issues are still to be solved: for instance, it remains fully unresolved whether wildlife can best be protected through the promotion of human economic development or through integral conservation of important biodiversity areas.



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Molecular Characterization of a Series of Solitary Fibrous Tumors, including Immunohistochemical expression of STAT6 and NATB2-STAT6 Fusion Transcripts, using Reverse Transcriptase(RT)–Polymerase Chain Reaction(PCR) Technique: An Indian Experience

Publication date: Available online 26 August 2017
Source:Pathology - Research and Practice
Author(s): Bharat Rekhi, Omshree Shetty, Parul Tripathi, Prachi Bapat, Mukta Ramadwar, Jyoti Bajpai, Ajay Puri
A solitary fibrous tumor (SFT) is characterized by a diverse clinicopathologic spectrum. Recent studies have unraveled STAT6 as a useful diagnostic immunohistochemical (IHC) marker for a SFT and NAB2-STAT6 as its specific gene fusion transcript.Thirty-three SFTs were tested for STAT6 immunostaining by polymer detection technique. STAT6 immunoexpression was further graded, based on intensity (mild, moderate and strong) and percentage of immunopositive tumor cells, ranging from 1–25%(1+); 26–50%(2+); 51–75%(3+) and in more than 75%(4+) tumor nuclei.These cases along with 17 other tumors were tested for 8 variants of NAB2-STAT6, using qualitative endpoint reverse-transcriptase (RT)-PCR technique. RNA extraction was performed using Recover All Total nucleic acid extraction kit. The selected cases were screened for all the 8 fusion variants, using 8 primer pairs for NAB2 and STAT6 genes.Thirty-three SFTs occurred in 18 men and 15 women (M: F=1.2:1), with age varying from 13–74 years(average=49.6); across various body sites. Immunohistochemically, most SFTs (30/33) (90.9%) displayed moderate to strong immunostaining for STAT6, including 3+ and 4+ immunostaining patterns in 27/33 (81.8%) tumors. By RT-PCR, 30/33(90.9%) cases of SFT were positive for NAB2-STAT6 fusions, including NAB2ex4/STAT6ex2 (7cases), NAB2ex7/STAT6ex2 (7cases), NAB2ex6/STAT6ex3 (6cases), NAB2ex6/SAT6ex16 (4cases), NAB2ex3/STAT6ex19 (4cases), NAB2ex6/STAT6ex17 (single case), NAB2ex4/STAT6ex4 (single case) and NAB2ex6/STAT6ex18 (none). NAB2-STAT6 fusions were not observed in 9 cases of synovial sarcoma, 4 of Ewing sarcoma, 2 of MPNST and 2 cases of dedifferentiated liposarcomas (100% specificity). On comparing with clinical outcomes, more cases (7/11)(63.6%) of classic SFT were associated with favorable outcomes, while more cases(5/8)(62%) of atypical and malignant SFTs were associated with aggressive outcomes.This study reinforces high sensitivity and specificity of NAB2-STAT6 fusion and its correlation with strong and diffuse IHC expression of STAT6 in a SFT, irrespective of its occurrence in various body sites and its histopathologic types. NAB2ex4-STAT6ex2 and NAB2ex7-STAT6ex2 fusions were relatively more frequently observed in our patients. Atypical and malignant SFTs, together, were more frequently associated with relatively aggressive clinical outcomes.



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Congenital Absence of the Palmaris Longus Muscle: A Meta-Analysis Comparing Cadaveric and Function Studies

The aim of our paper was to provide comprehensive data on the prevalence of absence of palmaris longus muscle (PLM) and its anatomical characteristics, and conduct two separate meta-analyses comparing cadaveric and functional studies while identifying variation among different ethnic groups. An extensive search was conducted through the major electronic databases to identify eligible articles. Data extracted included prevalence of absence of palmaris longus muscle among subjects, ethnicity, laterality, side and gender.

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Intensity-modulated radiotherapy in head and neck cancer — an update for oral and maxillofacial surgeons

Intensity-modulated radiation therapy (IMRT), a relatively new method of delivering radiotherapy, can precisely target a point within a specific tumour and reduce the dose to nearby anatomical structures. This is particularly important in the head and neck where radiotherapy can easily and irreparably damage the salivary glands, spinal cord, and eyes, and where, with increasingly better outcomes and survival, late complications of conventional radiotherapy (including osteoradionecrosis of the cervical spine) can be difficult to manage.

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Diagnostic dilemma between medication-related osteonecrosis and oral squamous cell carcinoma in a mandibular lytic lesion

Osteolytic lesions of the mandible are common, and there are two important differential diagnoses that must be considered: medication-related osteonecrosis of the jaws (MRONJ) and squamous cell carcinoma (SCC). In patients with a history of taking antiresorptive medication as well as risk factors for neoplasia it can be difficult to differentiate between the two. We describe two cases in both of which a mandibular osteolytic lesion was inadequately identified as either MRONJ or SCC because of confusing clinical and histopathological features.

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Angiotensin AT1 receptors modulate the anxiogenic effects of angiotensin (5-8) injected into the rat ventrolateral periaqueductal gray

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Publication date: Available online 26 August 2017
Source:Peptides
Author(s): Karina Genaro, Débora Fabris, Helene A. Fachim, Wiliam A. Prado
Losartan and PD 123,319 are non-peptide angiotensin (Ang) receptor antagonists for the AT1 and AT2 subtypes of Ang II receptors, respectively. The tetrapeptide Ang (5-8) is the smallest Ang-peptide that elicits anxiogenic effects on unconditioned and conditioned experimental models upon injection into the ventrolateral column of the periaqueductal gray (vlPAG), and Ang (5-8) can be synthesized (from Ang II or Ang III) and inactivated in this mesencephalic structure. The vlPAG is also known to play a central role in mechanisms of fear and anxiety. We therefore utilized male Wistar rats to examine the effects of losartan and PD 123,319 injections, selective antagonists of the AT1 and AT2 receptors, respectively, into the vlPAG in the elevated plus-maze, a classic rat model of anxiety, and against the anxiogenic effect of Ang (5-8) (0.4 nmol/0.25μL) upon injection into the same region. The anxiolytic profile was dependent on the dose of intra-vlPAG losartan, whereas no effects on experimental anxiety were observed in the plus-maze following PD 123,319 injection. The anxiogenic effect of Ang (5-8) injection into the vlPAG remained unchanged in the PD 123,319-pretreated rats, but the effect did not occur in losartan-pretreated rats. The results led us to suggest that the anxiogenic effect of Ang (5-8) injection into the vlPAG may depend on the local activation of AT1, but not AT2 receptors. Activation of AT1 receptors in structures nearby vlPAG may be tonically involved in fear and experimental anxiety.



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Association of down-regulation of calcitonin gene-related peptide and substance P with increase of myocardial vulnerability in diabetic neuropathic rats

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Publication date: Available online 26 August 2017
Source:Peptides
Author(s): Tu-Ping Li, Zheng Guo, Chao-Jie Liu, Tao Sun, Lu Chen, Xin Zhao
Diabetic patients present high co-morbidities of neuropathy and severer consequences of coronary heart disease. But the pathological mechanism is still unclear. Here we investigated a potential association of diabetic impairment of sensory nerves with increase of vulnerability of myocardium in acute myocardial ischemia/reperfusion. A rat model of diabetes mellitus was induced by high fat and sugar diet plus a small dose of streptozotocin. Impairment of sensory nerves was evaluated by measurement of changes in tail flick latency to noxious thermal stimulation and calcitonin gene-related peptide (CGRP) and substance P (SP) in the dorsal root ganglia (DRG) and the myocardium of the heart were examined. The myocardial injury was examined by infarct size, apoptosis ratio of cardiomyocytes and cardiac troponin I in the animals underwent acute myocardial ischemia (for 30min) and reperfusion (for 120min). The effects of CGRP and SP on cardiomyocyte injury induced by high glucose and hypoxia/reoxygenation were tested in cultured myocytes. The diabetic animals presented significant elevation of noxious thermal threshold with obvious reduction of the contents of CGRP and SP in the DRG and the myocardium. Importantly, the diabetic animals showed significant increases of infarct size, myocyte apoptosis and serum cardiac troponin I after acute myocardial ischemia/reperfusion, compared to the non-diabetic control. Furthermore, exogenously administered CGRP and SP attenuated the myocyte injury induced by the high concentration of glucose and hypoxia/reoxygenation. These findings suggested that impairment of sensory nerves with significant reduction of CGRP and SP in DRG, ventricular myocardium and serum may be associated with increase of myocardial vulnerability in acute myocardial ischemia/reperfusion in streptozotocin-induced diabetic rats.



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Exploration of variations in proteome and metabolome for predictive diagnostics and personalized treatment algorithms: Innovative approach and examples for potential clinical application

Publication date: Available online 26 August 2017
Source:Journal of Proteomics
Author(s): Xianquan Zhan, Ying Long, Miaolong Lu
Genome mutually interacts with internal and external environmental factors to result in different phenome that contains two important elements of proteins and metabolites, which link genome to predictive, preventive and personalized medicine (PPPM) or precision medicine (PM). Proteomic variations are the final presentation of the genomic and transcriptomic variations, and are involved in a wide range of variations including copy number of protein, splicing, post-translational modifications, translocation/re-distribution, spatial conformation, and pathway-network systems. Metabolomic variations are the comprehensive results originated from all types of in vivo substances, and are involved in a wide range of alterations of metabolites generated from sugars, lipids, proteins, and nucleic acids, and metabolic network systems. Currently the studies on variations in proteome and in metabolome are much insufficient in the width and depth in the fields of proteomics and metabolomics. The development of high-throughput, high-sensitivity, and especially high-reproducibility approaches is necessary to maximize the coverage of variations in proteome and in metabolome. The studies of proteomic and metabolomic variations directly result in the discovery of effective biomarkers to clarify molecular mechanisms of a disease, determine reliable therapeutic targets, and benefit precise prediction, diagnosis, and prognosis assessment. It has more important scientific values in PPPM or PM.Biological significance1. Complexity and importance of proteomic variations for PPPM, and the strategies and methodology to measure proteomic variations.2. Complexity and importance of metabolomic variations for PPPM, and the strategies and methodology to measure metabolomic variations.3. Proteome and metabolome are the important components that contribute to phenome. Clarification of variations in phenome is the key step to realize PPPM practice.

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Changes in protein abundance and activity involved in freezing tolerance acquisition in winter barley (Hordeum vulgare L.)

Publication date: Available online 25 August 2017
Source:Journal of Proteomics
Author(s): Gabriela Gołębiowska-Pikania, Przemysław Kopeć, Ewa Surówka, Monika Krzewska, Ewa Dubas, Anna Nowicka, Marcin Rapacz, Magdalena Wójcik-Jagła, Sabina Malaga, Iwona Żur
The changes in protein abundance induced by cold hardening were analysed by 2 DE in ten doubled haploid (DH) lines of winter barley, highly differentiated with respect to freezing tolerance level. Among 45 differential proteins identified by MALDI-TOF/TOF, the majority was classified as related to photosynthesis, carbohydrate metabolism, oxidation-reduction reactions and stress response. Among the detected proteins, higher abundance of RuBisCO large and small subunits, RuBisCO activase, two Oxygen-evolving enhancer proteins, Ferredoxin-NADP reductase, Cytochrome P450-dependent fatty acid hydroxylase and 14-3-3 protein was associated with higher freezing tolerance level. Lower relative level of hypothetical ATP synthase beta subunit, uncharacterized mitochondrial protein AtMg00810 and ribosomal RNA small subunit methyltransferase G also seems to be important.The results of proteomic studies were complemented by the evaluation of photosynthetic apparatus acclimation, showing distinctive differences between the studied genotypes in the number of active PSII reaction centres (RC/CSm). Additionally, the analysis of antioxidative enzyme activities suggests the importance of H2O2 as a signalling molecule possibly involved in the initiation of cold-induced plant acclimation. However, in DH lines with high freezing tolerance, H2O2 generation during cold hardening treatment was accompanied by more stable activity of catalase, H2O2-decomposing enzyme.SignificanceIn the study, the changes in protein abundance induced by cold hardening treatment were analysed by two-dimensional gel electrophoresis in ten doubled haploid (DH) lines of winter barley. Harnessing DH technology resulted in distinctive widening of genetic variation with respect to freezing tolerance level. Both the cold-hardening effect on the protein pattern in an individual winter barley DH line as well as the variation among the selected DH lines were investigated, which resulted in the identification of 45 differentiated proteins classified as involved in 14 metabolic pathways and cellular processes. Among them, eight proteins: (1) the precursor of RuBisCO large subunit, (2) RuBisCO small subunit (partial), (3) RuBisCO activase small isoform, (4) the precursor of Oxygen-evolving enhancer protein 1-like (predicted protein), (5) Oxygen-evolving enhancer protein 2, (6) the leaf isozyme of Ferredoxin-NADP reductase, (7) hypothetical protein M569_12509 Cytochrome P450-dependent fatty acid hydroxylase-like and (8) hypothetical protein BRADI_1g11290 (14-3-3 protein A-like) were accumulated to a higher level in leaves of cold-hardened seedlings of freezing tolerant winter barley DH lines in comparison with susceptible ones. Three others: (9) hypothetical protein BRADI_5g05668 F1 ATP synthase beta subunit-like, (10) predicted protein uncharacterized mitochondrial protein AtMg00810-like and (11) BnaA02g08010D Ribosomal RNA small subunit methyltransferase G-like were detected at lower level in freezing tolerant seedlings in comparison with susceptible genotypes. The last two were for the first time linked to cold acclimation. The results of complementary analyses indicate that PSII activity and stability of antioxidative enzymes under low temperature are also very important for freezing tolerance acquisition.

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Effects of Fe and Mn deficiencies on the protein profiles of tomato (Solanum lycopersicum) xylem sap as revealed by shotgun analyses

Publication date: Available online 25 August 2017
Source:Journal of Proteomics
Author(s): Laura Ceballos-Laita, Elain Gutierrez-Carbonell, Daisuke Takahashi, Anunciación Abadía, Matsuo Uemura, Javier Abadía, Ana Flor López-Millán
The aim of this work was to study the effects of Fe and Mn deficiencies on the xylem sap proteome of tomato using a shotgun proteomic approach, with the final goal of elucidating plant response mechanisms to these stresses. This approach yielded 643 proteins reliably identified and quantified with 70% of them predicted as secretory. Iron and Mn deficiencies caused statistically significant and biologically relevant abundance changes in 119 and 118 xylem sap proteins, respectively. In both deficiencies, metabolic pathways most affected were protein metabolism, stress/oxidoreductases and cell wall modifications. First, results suggest that Fe-deficiency elicited more stress responses than Mn deficiency, based on the changes in oxidative and proteolytic enzymes. Second, both nutrient deficiencies affect the secondary cell wall metabolism, with changes in Fe deficiency occurring via peroxidase activity, and in Mn deficiency involving peroxidase, Cu-oxidase and fasciclin-like arabinogalactan proteins. Third, the primary cell wall metabolism was affected by both nutrient deficiencies, with changes following opposite directions as judged from the abundances of several glycoside-hydrolases with endo-glycolytic activities and pectin esterases. Fourth, signaling pathways via xylem involving CLE and/or lipids as well as changes in phosphorylation and N-glycosylation also play a role in the responses to these stresses.Biological significanceIn spite of being essential for the delivery of nutrients to the shoots, our knowledge of xylem responses to nutrient deficiencies is very limited. The present work applies a shotgun proteomic approach to unravel the effects of Fe and Mn deficiencies on the xylem sap proteome. Overall, Fe deficiency seems to elicit more stress in the xylem sap proteome than Mn deficiency, based on the changes measured in proteolytic and oxido-reductase proteins, whereas both nutrients exert modifications in the composition of the primary and secondary cell wall. Cell wall modifications could affect the mechanical and permeability properties of the xylem sap vessels, and therefore ultimately affect solute transport and distribution to the leaves. Results also suggest that signaling cascades involving lipid and peptides might play a role in nutrient stress signaling and pinpoint interesting candidates for future studies. Finally, both nutrient deficiencies seem to affect phosphorylation and glycosylation processes, again following an opposite pattern.

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Chronic Traumatic Encephalopathy-Integration of Canonical Traumatic Brain Injury Secondary Injury Mechanisms with Tau Pathology

Publication date: Available online 26 August 2017
Source:Progress in Neurobiology
Author(s): Jacqueline R. Kulbe, Edward D. Hall
In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, football, football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression.

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In reply to: letter to the editor entitled: primary pure lymphoepithelioma-like carcinoma of the ureter



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Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas

Abstract

Chordomas are rare, slowly growing, locally aggressive bone neoplasms that arise from embryonic remnants of the notochord, showing dual epithelial-mesenchymal differentiation. The high plasticity probably is the main reason for the high variety in phenotypes of chordoma, from its high heterogeneity on a cellular level to its subtype variations depending on tissue location, with its potential to develop from an inactive quiescent form to an aggressive cancer with extreme adaptability and resistance to drugs and other treatments. Gene expression profiles of formalin-fixed, paraffin-embedded skull chordoma, spine chordoma, and normal tissue specimens were generated and compared. Using strict criteria, we identified 222 differentially expressed transcripts unique to skull base chordoma, 261 unique to spine chordoma, and 192 common to both chordoma subtypes. Further analysis of these three groups of transcripts allowed the selection of three subsets of highly differentially expressed genes as potential biomarkers, disease drivers, and therapeutic targets in both chordoma subtypes. Immunohistochemistry revealed LMX1A to be dominant in skull base chordoma, SALL3 to be unique to spine chordoma, and T to be common to both chordoma subtypes. In both chordoma subtypes, the genes with the highest expression were predominantly development-related genes, mostly transcription factors. Our findings indicate that these developmental genes play important oncogenic roles in chordoma, mainly causing high plasticity and resistance to therapy in both these cancer subtypes but also determining their differentiation status and proliferation activity, pointing to features expected of heterogeneous stem cell-like tissues with similarities to their notochord origins.



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Curative-intent treatment of recurrent colorectal liver metastases: a comparison between ablation and resection

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Publication date: Available online 26 August 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Aurélien Dupré, Robert P. Jones, Rafael Diaz-Nieto, Stephen W. Fenwick, Graeme J. Poston, Hassan Z. Malik
BackgroundLiver-limited recurrence after resection of colorectal liver metastases is a frequent occurrence, and can in some cases be treated with curative intent. Although surgical re-resection remains standard of care, there is growing interest in the role of ablation in this setting. The aim of this study was to compare the outcomes after curative-intent ablation and resection in patients with recurrent colorectal liver metastases.MethodsWe retrospectively analysed data from 366 consecutive patients who underwent liver resection for colorectal liver metastases between June 2010 and August 2015. Sixty-four developed liver-limited recurrence which was treated with curative intent, thirty-three (51.6%) by ablation and 31 (48.4%) by repeat resection.ResultsPatient groups were well matched, with surgically resected patients showing higher pre-operative carcinoembryonic antigen levels and larger metastases. There were fewer post-operative complications and shorter length of stay in the ablation group (p<0.02). After a median follow-up of 36.2 months, median overall survival was the same for both the resected and ablated groups at 33.3 months. Median progression-free survival was longer for patients treated with surgery (10.2 months) compared to ablation (4.3 months) (p=0.002).ConclusionsAblation or resection for liver-limited recurrence after surgery for colorectal liver metastases is associated with improved overall survival compared with systemic chemotherapy alone, and should always be considered for patients with resectable liver recurrence. Although ablation seemed to be associated with a shorter progression-free survival, post-procedure morbidity was significantly lower. The choice between ablation and resection should therefore be made on a personalised basis.



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Table of Contents

Publication date: September–October 2017
Source:Clinical Imaging, Volume 45





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Clinical Imaging: Past, Present and Future

Publication date: September–October 2017
Source:Clinical Imaging, Volume 45





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IOP-details

Publication date: September 2017
Source:International Journal of Psychophysiology, Volume 119





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Full title with Editorial board members

Publication date: September 2017
Source:International Journal of Psychophysiology, Volume 119





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Instructions to Authors

Publication date: September 2017
Source:International Journal of Psychophysiology, Volume 119





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Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)

Publication date: Available online 26 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Writing Group, A.R. Naylor, J.-B. Ricco, G.J. de Borst, S. Debus, J. de Haro, A. Halliday, G. Hamilton, J. Kakisis, S. Kakkos, S. Lepidi, H.S. Markus, D.J. McCabe, J. Roy, H. Sillesen, J.C. van den Berg, F. Vermassen, ESVS Guidelines Committee, P. Kolh, N. Chakfe, R.J. Hinchliffe, I. Koncar, J.S. Lindholt, M. Vega de Ceniga, F. Verzini, ESVS Guideline Reviewers, J. Archie, S. Bellmunt, A. Chaudhuri, M. Koelemay, A.-K. Lindahl, F. Padberg, M. Venermo




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European Society for Vascular Surgery Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease

Publication date: Available online 26 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): H.-H. Eckstein




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2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)

Publication date: Available online 26 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Authors/Task Force Members, Victor Aboyans, Jean-Baptiste Ricco, Marie-Louise E.L. Bartelink, Martin Björck, Marianne Brodmann, Tina Cohnert, Jean-Philippe Collet, Martin Czerny, Marco De Carlo, Sebastian Debus, Christine Espinola-Klein, Thomas Kahan, Serge Kownator, Lucia Mazzolai, A. Ross Naylor, Marco Roffi, Joachim Röther, Muriel Sprynger, Michal Tendera, Gunnar Tepe, Maarit Venermo, Charalambos Vlachopoulos, Ileana Desormais, Document Reviewers, Petr Widimsky, Philippe Kolh, Stefan Agewall, Héctor Bueno, Antonio Coca, Gert J. De Borst, Victoria Delgado, Florian Dick, Cetin Erol, Marc Ferrini, Stavros Kakkos, Hugo A. Katus, Juhani Knuuti, Jes Lindholt, Heinrich Mattle, Piotr Pieniazek, Massimo Francesco Piepoli, Dierk Scheinert, Horst Sievert, Iain Simpson, Jakub Sulzenko, Juan Tamargo, Lale Tokgozoglu, Adam Torbicki, Nikolaos Tsakountakis, José Tuñón, Melina Vega de Ceniga, Stephan Windecker, Jose Luis Zamorano




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Determination of the content of selected elements in medieval waterlogged oak wood from the Lednica Lake—a case study

Abstract

The content of selected elements: Al, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Sb, Si, Ti, V and Zn was determined in archaeological waterlogged oak wood from the Lednica Lake by using the inductively coupled plasma optical emission spectrometry (ICP-OES) method. The concentration of metals (especially heavy metals) in wood is typically specified to characterise this material and evaluate the possibility to use it for industrial purposes. In case of waterlogged archaeological wood intended for further research on new methods of conservation, such an analysis is important for other reasons. As it has been confirmed by numerous conservators and researchers, the presence of metal compounds is a serious problem not only due to their destructive influence on wood tissue but also from a conservation/re-conservation perspective. Metal-containing chemicals may influence conservation treatments by reacting with substances used for wood conservation and causing irreversible damage to wooden objects. Therefore, while developing new solutions for wood conservation, a broad knowledge not only on the state of wood preservation and deterioration but also on interacting chemical factors is required. The results of the research clearly show that content of minerals in waterlogged wood excavated from the bottom of the Lednica Lake considerably exceeded the average percentage of these elements in contemporary wood, which is associated with the mineralisation process. Moreover, variability in metal content was observed between waterlogged and contemporary wood. In waterlogged wood, the highest concentrations of Ca, Fe, Mg and P were observed, while in contemporary oak wood the predominant concentrations of K, Ca, Mn and Si were determined. Statistical analysis showed the variability in content of elements between different archaeological wood zones and contemporary wood. On the basis of the results obtained, it could be concluded that the studied waterlogged wood acted as an adsorbent of elements from water and sediments. High content of metal ions can be an impediment in developing new formulations for conservation, while using this wood as an experimental material. Therefore, while planning to use new chemicals as conservation agents, the possible interactions between chemicals and metals must be taken into consideration.



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Pediatric soft tissue tumor of the upper arm with LMNA-NTRK1 fusion

Publication date: Available online 26 August 2017
Source:Human Pathology
Author(s): Shinji Kohsaka, Tsuyoshi Saito, Keisuke Akaike, Yoshiyuki Suehara, Takuo Hayashi, Tatsuya Takagi, Kazuo Kaneko, Toshihide Ueno, Shinya Kojima, Ken-ichi Kohashi, Hiroyuki Mano, Yoshinao Oda, Takashi Yao
A 6-year-old girl was admitted to our hospital due to the presence of a slow-growing tumor in her right elbow. Biopsy specimens showed a round- to spindle-cell neoplasm with uncertain malignant potential, leading to the decision of surgical resection. Histologically, the resected tumor was encapsulated by fibrous tissue, but focally invaded the surrounding skeletal muscles. The tumor was composed of ganglion-cell-like short spindle cells with lymphocytic infiltration in the collagenous background. Tumor cells with large bizarre nuclei were occasionally observed, and multinucleated giant cells were scattered at the periphery. Hemangiopericytoma-like patterns and adipose tissue elements were not evident, and mitotic figures were rarely observed (<1 per 10 high-power fields). Immunohistochemically, the tumor cells were positive for S-100 and CD34 and focally positive for EMA and AE1/AE3. RNA sequencing and subsequent RT-PCR revealed alternative splicing forms of LMNA-NTRK1 fusion (Ex2-Ex10 and Ex2-Ex15).



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Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma

Publication date: Available online 26 August 2017
Source:Human Pathology
Author(s): Min-Kyung Yeo, Song-Yi Choi, In-Ock Seong, Kwang-Sun Suh, Jin Man Kim, Kyung-Hee Kim
Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non-small cell lung carcinoma (NSCLC) patients for treatment with anti-PD-1 or anti-PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263 and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive a 22C3 PD-L1 labelling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases.



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Aldehyde dehydrogenase 1 (ALDH1A1) expression by immunohistochemistry is associated with chemo-refractoriness in patients with high-grade ovarian serous carcinoma

Publication date: Available online 26 August 2017
Source:Human Pathology
Author(s): Madhuchhanda Roy, Joseph Connor, Ahmed Al-Niaimi, Stephen L Rose, Aparna Mahajan
Aldehyde dehydrogenase-1A1 (ALDH1A1), CD133, CD44, and CD24 have been reported as cancer stem cell markers in ovarian cancers. The goal of our study was to assess the prognostic significance of these markers in patients with advanced serous ovarian cancer. Formalin-fixed, paraffin-embedded tissues from 347 ovarian cancer were used to construct a microarray. Immunohistochemical studies for ALDH1A1, CD133, CD44, and CD24 were performed and scored semiquantitatively by two pathologists based on intensity and percent of positive immunoreactive cells. Immunohistochemistry was compared to clinical parameters and survival. Of the 347 cases, early stage disease, nonserous tumors, cases with incomplete therapy, and cores with no tumor were excluded. Immunohistochemistry was interpretable in 124 of the 136 stage III and IV ovarian serous carcinoma. ALDH1A1, CD24, and CD44 were variably detected in both tumor and stromal cells, and immunoreactivity in tumor was stronger than in stromal cells. CD133 immunoreactivity was not quantified due to nonspecific staining in tumor and stroma. Statistical analyses using χ2 and Student's t test revealed that ALDH1A1-positive (n=53) carcinoma were 3 times more likely to demonstrate platinum refractoriness than ALDH1A1-negative (n=71) tumors (17% vs 6%, respectively; P=.04); however, neither progression-free or overall survival was influenced by ALDH1A1 status in this cohort. The expression of CD44 and CD24 had no clinicopathological associations in the present study. Our study supports that ALDH1A1 expression is associated with poor response to platinum-based therapy in patients with high-grade ovarian serous carcinoma. Further study of this relationship is needed to understand how this could impact clinical care.



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J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma

Publication date: Available online 26 August 2017
Source:Human Pathology
Author(s): Erika M. Moore, Steven H. Swerdlow, Sarah E. Gibson
Although most classical Hodgkin lymphomas (CHL) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHL are positive for these antigens. We investigated the utility of J chain and MEF2B in the diagnosis of CHL, NLPHL, PMBL, T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL), and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (BCLU, DLBCL/CHL) compared to OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHL and were negative in 43/43 (100%) CHL. 14/15 (93%) PMBL and 4/4 (100%) TCRLBL were MEF2B-positive, while 67% of PMBL and 50% of TCRLBL were J chain-positive. 3/3 BCLU, DLBCL/CHL were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL, are particularly useful in highlighting LP cells, and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas.



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THYMOMA: A clinicopathological correlation of 1470 cases

Publication date: Available online 26 August 2017
Source:Human Pathology
Author(s): Annikka Weissferdt, Neda Kalhor, Justin A. Bishop, Se Jin Jang, Jae Ro, Fredrik Petersson, Bingcheng Wu, Gerald Langman, Hollie Bancroft, Yalan Bi, Yunxiao Meng, Filomena Medeiros, Hans Brunnstrom, Dominic Spagnolo, Siaw Ming Chai, Andrew Laycock, Paul E. Wakely, Goran Elmberger, Fernando A. Soares, Antonio H. Campos, Derya Gumurdulu, Isabel Alvarado-Cabrero, Domenico Coppola, Arlene M. Correa, David Rice, Reza J. Mehran, Boris Sepesi, Garrett Walsh, Larry Kaiser, Cesar A. Moran
We present 1470 surgical resections for thymoma identified in the pathology files of 14 institutions from 11 countries with the purpose to determine and correlate a simplified histological classification of thymoma and pathological staging with clinical outcome. The study population was comprised of 720 men and 750 women between the ages of 12 and 86years (average: 54.8years). Clinically 137 patients (17%) had a history of myasthenia gravis, 31 patients (3.8%) of other autoimmune disease, and 55 (6.8%) patients of another neoplastic process. Surgical resection was performed in all patients. Histologically, 1284 (87.13%) cases were thymomas (World Health Organization [WHO] types A, B1, and B2, and mixed histologies), and 186 (12.7%) were atypical thymomas (WHO type B3). Of the entire group, 630 (42.9%) were encapsulated thymomas and 840 (57.9%) were invasive thymomas in different stages. Follow-up information was obtained in 1339 (91%) patients, who subsequently were analyzed by univariate and multivariate statistical analysis. Follow-up ranging from 1 to 384months was obtained (mean: 69.2months) showing tumor recurrence in 136 patients (10.1%), while 227 died- 64 (28.2%) due to tumor and 163 (71.8%) due to other causes. Statistical analysis shows that separation of these tumors into- thymoma and atypical thymoma- is statistically significant (P=.001), while tumor staging into categories of encapsulated, minimally invasive, and invasion into adjacent organs offers a meaningful clinical assessment with a p=value of 0.038. Our findings suggest that our simplified histological schema and pathological staging system are excellent predictors of clinical outcome.



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The role of enteric neurons in the development and progression of colorectal cancer

Publication date: Available online 25 August 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Glenn Rademakers, Nathalie Vaes, Simone Schonkeren, Alexander Koch, Keith A. Sharkey, Veerle Melotte
The enteric nervous system (ENS) is the neural network belonging to the gastrointestinal tract, which is essential for regulating gut functions. The importance of the ENS is underscored by the existence of severe gastrointestinal diseases, such as Hirschsprung's disease and intestinal pseudo-obstruction, which arise when the ENS fails to develop normally or becomes dysregulated. Moreover, it is known that enteric neurons are involved in intestinal inflammation and gut homeostasis. So far, the role of the ENS in colorectal cancer (CRC) carcinogenesis remains poorly understood, even though processes like perineural invasion and neoneurogenesis are important factors in the CRC field. Here we summarize how enteric neurons are affected during CRC and discuss the influence of enteric neurons, either direct or indirect, on CRC development and/or progression. Finally, we illustrate how the ENS could be targeted as a potential anti-cancer therapy, establishing the ENS as an integral part of the tumor microenvironment.



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Editorial Board & Aims and Scope

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Publication date: August 2017
Source:Nano Today, Volume 15





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Estradiol (E2)- and Tamoxifen (Tmx)-Bound ER-alpha (ERα) Interact Differentially with Histone Deacetylases 1 and 3 (HDACs 1 and 3)

Publication date: Available online 25 August 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Dharmendra Sharma, Yuan Liu, Rosalie M. Uht
Although ERα activation properties have been intensively studied, this is not the case for their repressive properties. In this report, the ERα ligand binding domain (LBD) is shown to interact both with a deacetylase function and with HDAC1 and HDAC3. Ligands do not affect binding to the deacetylase activity or to HDAC1. In distinction, E2 reduced LBD binding to HDAC3, whereas Tmx had no effect. Knock-down of either HDAC1 or 3 led to increased transcriptional activity by both HDACs, presumably by decreased repression. In distinction, only HDAC3 knock-down led to increased activity in the presence of Tmx. In summary, ERα differentially interacts with HDACs 1 and 3 to regulate transcriptional activity.



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Role and mechanism of AMH in the regulation of Sertoli cells in mice

Publication date: Available online 26 August 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Zia ur Rehman, Tesfaye Worku, John S. Davis, Hira Sajjad Talpur, Dinesh Bhattarai, Ishwari Kadariya, HuaGua Hua, Jing Cao, Rahim Dad, Farmanullah, Tarique Hussain, Liguo Yang
Sertoli cells produce anti-Müllerian hormone (AMH), a glycoprotein belonging to the transforming growth factor-beta family. AMH mediates the regression of Müllerian ducts in the developing male fetus. However, the role of AMH in the regulation of primary Sertoli cells remains unclear. The present study was designed to investigate the effect of AMH on the viability and proliferation of Sertoli cells, with an additional focus on stem cell factor (SCF). Treatment of Sertoli cells with increasing concentrations of rh-AMH (0, 10, 50, 100, and 800ng/ml) for two days revealed that AMH, at high concentrations, increased apoptosis. These results were confirmed by a significant increase in Caspase-3 and Bax and a decrease in Bcl-2 protein and mRNA expression (P<0.01). Paradoxically, treatment with a low concentration of rh-AMH (10ng/ml), but not higher concentrations (50–800ng/ml), promoted Sertoli cell proliferation, which was verified by an increase in PCNA mRNA (P <0.05). Furthermore, only low concentrations of rh-AMH activated the non-canonical ERK signaling pathway. Similarly, low concentrations of rh-AMH (10–50ng/ml) significantly increased (P <0.05) SCF mRNA and SCF protein levels. These findings indicate that AMH differentially regulates the fate of Sertoli cells in vitro by promoting proliferation at low concentrations and apoptosis at high concentrations. In addition, AMH increased the expression of SCF, an important regulator of Sertoli cell development. Therefore, AMH may play a role in Sertoli cell development.



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Efficacy of Hybrid Vitamin D Receptor Agonist/Histone Deacetylase Inhibitors in Vitamin D-Resistant Triple-Negative 4T1 Breast Cancer

Publication date: Available online 25 August 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Krikor Bijian, Dainis Kaldre, Tian-Tian Wang, Manuella Bouttier, Annie Boucher, Moulay Alaoui-Jamali, John H. White, James L. Gleason
Hormonal 1,25-dihydroxyvitamin D (1,25D) and its analogues have shown efficacy in some preclinical models of cancer. However, many models are resistant to the antiproliferative effects of 1,25D or its analogues in vitro or in vivo, and such compounds have failed in the clinic as monotherapies because of tumor resistance. Given the observed synergism between 1,25D analogues and histone deacetylase inhibitors (HDACi) in 1,25D-resistant cells, we previously developed a series of hybrid secosteroidal and easily assembled non-secosteroidal analogues that combined agonism for the vitamin D receptor and HDACi in a single backbone. These compounds displayed enhanced efficacy against 1,25D-resistant malignant cells in vitro. Structure/function studies led to synthesis of several non-secosteroidal variants in which HDACi potency was optimized without substantially sacrificing VDR agonism. Here, we present the first studies of efficacy in vivo of two of these compounds, DK-366 and DK-406, in the aggressive mouse 4T1 model of triple-negative breast cancer, a form of the disease for which treatment options are limited. 4T1 cells are resistant in vitro to the cytostatic and cytotoxic effects of 1,25D and the potent HDACi SAHA individually up to concentrations of 1μM and 50μM, respectively, whereas combinations of the two are efficacious. In vitro, DK-366 or −406 induced dose-dependent arrest of cell proliferation and cytotoxicity at 10–20μM. In vivo, the maximum tolerated dose (MTD) of DK-366 and −406 were 2.5 and 5.0mg/kg, respectively. Although the compounds induced hypercalcemia at elevated doses, consistent with VDR agonism in vivo, they both reduced tumor burden at doses below their MTD's. Moreover, in a separate experiment, DK-406 at 5mg/kg reduced 4T1 lung metastases by at least 50%. Under the same conditions, 1,25D (0.25μg/kg) and SAHA (25mg/kg) combined had no effect on tumor burden or on lung metastases. These experiments show that hybrid compounds are bioavailable and efficacious against a particularly aggressive model of metastatic breast cancer, providing strong support for the therapeutic potential of the hybrid concept.



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Non-invasive method of monitoring retinal vasculitis in patients with birdshot chorioretinopathy using optical coherence tomography

Background/aims

To investigate the utility of using montaged optical coherence tomography (OCT) thickness maps to monitor perivascular thickness as a marker of vasculitic activity in patients with large-vessel retinal vasculitis.

Methods

This is a retrospective cohort study of 22 eyes of 11 patients with a history of retinal vasculitis associated with birdshot chorioretinopathy (BCR). Patients had serial spectral domain 6x6 mm cube OCT scans centred on the fovea, optic nerve and proximal branches of the superior and inferior retinal vessels. OCT thickness change maps for each respective region were analysed. Changes in perivascular thickness were confirmed by assessing vasculitic activity on fluorescein angiography (FA), when clinically indicated.

Results

In three patients, montaged OCT scans were acquired at diagnosis and serially through initial treatment. In all three patients, montaged OCT demonstrated reduced perivascular thickening with oral prednisone treatment, which was confirmed by FA showing reduced vascular leakage in both eyes. Eight patients had serial montaged OCT scans after diagnosis and initial treatment of BCR. Four of these patients showed fluctuations in perivascular thickness during flares and treatment that were confirmed by either increased or decreased vascular leakage on FA. The other four patients remained quiet on their immunosuppressive treatment regimens, and no changes in perivascular thickness were detected.

Conclusions

Evaluating large-vessel perivascular thickness on OCT scans may be a useful method for non-invasively monitoring posterior pole large-vessel retinal vasculitis.



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Multicentred international review of orbital exenteration and reconstruction in oculoplastic and orbit practice

Background

Orbital exenteration is a disfiguring procedure reserved for life-threatening malignancies. This study examines the clinical course and outcomes of a large series of patients who underwent orbital exenteration for malignant periocular neoplasms.

Methods

This is a retrospective review of patients who underwent orbital exenteration from 1 July 2005 to 30 June 2015 at four tertiary referral centres in the USA, Australia and Canada. Demographics, indication for surgery, pathology, surgical technique, reconstruction type and outcomes were reviewed.

Results

Orbital exenteration was performed on 102 patients. The mean age at surgery was 67.5 years. The most common malignant tumours encountered were squamous cell carcinoma, melanoma and basal cell carcinoma. Seventy-six patients (75%) underwent reconstruction with a local myocutaneous flap, twelve with partial-thickness skin grafts (PTSG), or split skin graft, two had a free flap, and one had a dermis fat graft. Sixteen patients had combined procedures of two of the above. Complete removal of the tumour was achieved with clear margins in 81 cases. Of all patients, 72% were alive at 48 months or more.

Conclusion

The majority of orbital exenterations performed in this series were secondary to periocular malignancies with unsuccessful/insufficient previous treatments. Regional myocutaneous flaps, PTSG, full-thickness skin grafts and dermis fat grafts were all highly effective and durable reconstructive options, and were able to withstand radiation therapy without complications.



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Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma

Background/aim

To evaluate the efficacy of intravitreal topotecan for refractory or recurrent vitreous seeds in retinoblastoma.

Methods

Intravitreal injection of topotecan hydrochloride (30 µg/0.15 mL) was provided every 3 weeks by the safety enhanced technique.

Results

The study included 17 consecutive patients with retinoblastoma with refractory or recurrent vitreous seeds. Five eyes (29%) belonged to International Classification of Retinoblastoma group C and 12 eyes (71%) belonged to group D. Primary treatment included triple drug intravenous chemotherapy for a mean of 10 cycles (median, 9 cycles; range, 6–18 cycles). Fifteen patients (88%) had undergone 56 periocular carboplatin injections with a mean of 4 injections (median, 3 injections; range, 1–8 injections), concurrent with intravenous chemotherapy. A total of 53 intravitreal topotecan injections were performed in 17 eyes of 17 consecutive patients with refractory or recurrent vitreous seeds with a mean of 3 injections (median, 3 injections; range, 2–6 injections). Complete regression of vitreous seeds was achieved in 17 of 17 eyes (100%). At a mean follow-up of 23.8 months (median, 24 months; range, 15.1–34.1 months), one eye (6%) with a recurrent retinal tumour needed enucleation, and the rest of the 16 eyes (94%) maintained complete regression. Final visual acuity could be reliably assessed in all 16 eyes (100%), of whom 12 eyes (75%) had visual acuity ≥20/200. None of the patients developed ocular or systemic complications.

Conclusion

Three-weekly intravitreal topotecan appears effective and safe in controlling focal or diffuse refractory or recurrent vitreous seeds in retinoblastoma.



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Active surveillance of choroidal neovascularisation in children: incidence, aetiology and management findings from a national study in the UK

Background/Aims

To determine the UK incidence, demographics, aetiology, management and visual outcome for children developing choroidal neovascularisation (CNV).

Methods

A prospective population-based observational study of routine practice via the British Ophthalmological Surveillance Unit between January 2012 and December 2013 with subsequent 1-year follow-up in children under 16 years old with newly diagnosed CNV.

Results

Twenty-seven children with CNV were reported. The UK estimated annual incidence for those aged 16 and under was 0.21 per 100 000 (95% CI 0.133 to 0.299). The mean age was 11.1 years (SD 3.9, range 4–16). Fourteen were female. Seventy-seven per cent (22 patients) were Caucasian British. Twenty-three children (85%) had unilateral disease. The most common aetiology included inflammatory retinochoroidopathy (n=9), optic disc abnormalities (n=9) and idiopathic (n=5). Optical coherence tomography was performed in all cases and fundus fluorescein angiography in 61%. Management included observation only (n=10), anti-vascular endothelial growth factor (anti-VEGF) injection of bevacizumab (n=14) or ranibizumab (n=2), or both (n=1), and additional use of oral (n=1) and local (periocular n=2 and intravitreal n=2) steroids in five children with inflammatory retinochoroidopathy. The mean number of anti-VEGF injections was 2±1, with eight patients receiving only one injection. The mean (SD) best corrected visual acuity in LogMAR was 0.91 (0.53) at presentation and 0.74 (0.53) at 1-year follow-up (p=0.09).

Conclusion

This is the first population-based prospective study of CNV in children. This is a rare disorder with a poor visual prognosis irrespective of CNV location and the use of anti-VEGF therapy.



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Traumatic brain injury, dry eye and comorbid pain diagnoses in US veterans

Aims

The purpose of the study is to evaluate the relationship between dry eye (DE) and pain diagnoses in US veterans with and without traumatic brain injury (TBI).

Methods

Retrospective cohort study of veterans who were seen in the Veterans Administration Hospital (VA) between 1 January 2010 and 31 December 2014. Veterans were separated into two groups by the presence or absence of an International Classification of Diseases, Ninth Revision diagnosis of TBI and assessed for DE and other comorbidities. A dendrogram was used to investigate the linkage between TBI, DE, chronic pain and other comorbid conditions.

Results

Of the 3 265 894 veterans seen during the 5-year period, 3.97% carried a diagnosis of TBI. Veterans with TBI were more likely to have a diagnosis of DE compared with their counterparts without TBI (37.2% vs 29.1%, p<0.0005). The association was stronger between TBI and ocular pain (OR 3.08; 95% CI 3.03 to 3.13) compared with tear film dysfunction (OR 1.09; 95% CI 1.07 to 1.10). Those with TBI were also about twice as likely to have a diagnosis of chronic pain, headache, depression or post-traumatic stress disorder compared with their counterparts without TBI. Cluster analysis of TBI, DE and pain diagnoses of interest revealed that central pain syndrome, cluster headache, sicca syndrome, keratoconjunctivitis sicca and late effect of injury to the nervous system (as can be seen after TBI) were all closely clustered together.

Conclusions

DE and pain disorders occur at higher frequencies in patients with a diagnosis of TBI, suggesting a common underlying pathophysiology.



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Pterygia are indicators of an increased risk of developing cutaneous melanomas

Aim

To investigate whether pterygium is an indicator of an increased risk of cutaneous melanoma (CM).

Methods

A matched-cohort study, using linked health administrative data sets to identify all hospital-treated pterygium in Western Australia (WA) between 1979 and 2014. We identified pterygium cases from hospital diagnosis and/or procedure International Classification of Diseases 9th revision (ICD-9) and 10th revision (ICD-10) codes and matched cases by age, sex and residential postcode to WA Electoral Roll controls with no known history of pterygium. Both cohorts were linked to the WA Cancer Registry and the WA Deaths Registry.

Results

23 625 people had pterygium treatment (64% male) in WA hospitals. The median age for pterygium diagnosis and/or treatment was 49 years (range 14–96). There were significantly more CM cases in the pterygium cohort compared with the control cohort (1083 vs 874; p<0.001). In a logistic regression analysis, there was a 24% increase in the odds of developing a CM in the pterygium cohort, compared with controls, after controlling for other predictors (OR 1.24, 95% CI 1.1 to 1.4). The incident rate ratio (IRR) of a malignant CM diagnosis was 20% greater in people who had treatment for a pterygium compared with controls (IRR 1.2, 95% CI 1.0 to 1.4).

Conclusion

The presence of a pterygium indicates a significantly increased risk of developing a CM. Eye care providers who see patients with developing pterygia should advise these patients of this increased risk and recommend regular skin surveillance.



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Cumulative retention rate of adalimumab in patients with Behcet's disease-related uveitis: a four-year follow-up study

Background/aims

Adalimumab (ADA) has been shown to be an effective treatment for Behcet's disease (BD)-related uveitis. We aimed at evaluating the cumulative retention rate of ADA during a 48-month follow-up period in patients with BD-related uveitis, the impact of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on ADA retention rate, and differences according to the various lines of biologic therapy (ie, first- vs second-line or more). Predictive factors of response to ADA were also investigated.

Methods

We enrolled patients diagnosed with BD-related uveitis and treated with ADA between January 2009 and December 2016. Cumulative survival rates were studied using the Kaplan-Meier plot, while the log-rank (Mantel-Cox) test was used to compare survival curves. Statistical analysis was performed to identify differences according to the response to ADA.

Results

54 consecutive patients (82 eyes) were eligible for analysis. The drug retention rate at 12- and 48-month follow-up was 76.9% and 63.5%, respectively. No statistically significant differences were identified according to the use of concomitant DMARDs (p=0.27) and to the different lines of ADA treatment (p=0.37). No significant differences were found between patients continuing and discontinuing ADA in terms of age (p=0.24), age at BD onset (p=0.81), age at uveitis onset (p=0.56), overall BD duration (p=0.055), uveitis duration (p=0.46), human leucocyte antigen-B51 positivity (p=0.51), and gender (p=0.47).

Conclusions

ADA retention rate in BD-related uveitis is excellent and is not affected by the concomitant use of DMARDs or by the different lines of biological therapy. Negative prognostic factors for BD uveitis do not impact ADA efficacy.



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Paracrine effects of mesenchymal stem cells on the activation of keratocytes

Aims

The purpose of this study is to investigate the impact of mesenchymal stem cell (MSC)-derived soluble factors on the function of keratocytes, with a particular focus on the processes involved in wound healing, including keratocyte activation, migration and proliferation as well as extracellular matrix (ECM) synthesis.

Methods

Primary cultured rabbit keratocytes were treated with MSC-conditioned medium (MSC-CM). The paracrine factors released by bone marrow MSCs were examined by ELISA. Time-lapse microscope was used to examine wound closure in vitro. Mouse model of corneal injury was made by epithelial scraping after ethanol injury.

Results

MSC-CM significantly increased the wound closure rate of corneal stromal cells in vitro. This enhancement of wound closure by MSC-CM was due to the promotion of cell migration. MSC-CM enhanced keratocyte survival following ethanol injury via inhibiting apoptosis. The expression of ECM component genes in keratocytes was upregulated by MSC-CM. In addition, MSC-CM promoted corneal epithelial wound healing following chemical injury. A number of wound healing mediators were detected in MSC-CM, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGFβ1), interleukin 8 (IL8), interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1).

Conclusion

MSC secretes certain factors that accelerate corneal re-epithelialisation. The paracrine effects of MSC on corneal wound healing including improvements in cell viability, migration and ECM formation.



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Laceration Management

Publication date: Available online 25 August 2017
Source:The Journal of Emergency Medicine
Author(s): Scott L. Mankowitz
BackgroundTraumatic lacerations to the skin represent a fairly common reason for seeking emergency department care. Although the incidence of lacerations has decreased over the past decades, traumatic cutaneous lacerations remain a common reason for patients to seek emergency department care.ObjectiveInnovations in laceration management have the potential to improve patient experience with this common presentation.DiscussionStudies have confirmed that delays in wound closure rarely confer increased rates of infection, although comorbidities such as diabetes, chronic renal failure, obesity, human immunodeficiency virus, smoking, and cancer should be considered. Antibiotics should be reserved for high-risk wounds, such as those with comorbidities, gross contamination, involvement of deeper structures, stellate wounds, and selected bite wounds. Topical anesthetics, which are painless to apply, have a role in select populations. In most studies, absorbable sutures perform similarly to nonabsorbable sutures and do not require revisit for removal. Novel atraumatic closure devices and expanded use of tissue adhesives for wounds under tension further erode the primacy of regular sutures in wound closure. Maintaining a moist wound environment with occlusive dressings is more important than previously thought. Most topical wound agents are of limited benefit.ConclusionsRecent innovations in wound closure are allowing emergency physicians to shift toward painless, atraumatic, and rapid closure of lacerations.



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Lymph node ratio relationship to regional failure and distant metastases in oral cavity cancer

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Publication date: August 2017
Source:Radiotherapy and Oncology, Volume 124, Issue 2
Author(s): Ali Hosni, Caitlin McMullen, Shao Hui Huang, Wei Xu, Jie Su, Andrew Bayley, Scott V. Bratman, John Cho, Meredith Giuliani, John Kim, Jolie Ringash, John Waldron, Anna Spreafico, Ilan Weinreb, John R. de Almeida, Dale H. Brown, Jonathan C. Irish, Brian O'Sullivan, David P. Goldstein, Andrew Hope
BackgroundWe aimed to investigate the impact of lymph node ratio (LNR, number of positive nodes/total number of excised nodes) on regional-only-failure, distant-only-failure and overall survival (OS) in oral squamous cell carcinoma (OSCC).MethodsRetrospective review of pN0-2 OSCC-patients (1994–2012) treated with curative-surgery with neck dissection±postoperative radiotherapy (PORT)±concurrent chemotherapy. LNR was subjected to multivariable analysis (MVA) of regional-only-failure, distant-only-failure and OS.ResultsOverall 914 patients were identified; median follow-up: 51months (1–189); pN0: 482 (52.7%), pN1: 128 (14%), pN2a: 6 (0.7%); pN2b: 225 (24.6%); pN2c: 73 (8%); median number of dissected nodes: 36 (6–125); median number of pN+: 2 (1–49); median LNR for pN+ patients: 6%; extranodal extension: 187 (20.5%). Bilateral neck dissection: 368 (40.3%); PORT: 452 (49.5%); and concurrent chemotherapy: 80 (8.8%). High grade, lymphovascular invasion perineural invasion and pT3–4 were associated with high LNR. On MVA, LNR was associated with regional-only-failure (HR=1.06; 95%CI: 1.04–1.08; p<0.001), distant-only-failure (HR=1.03; 95%CI: 1.02–1.05; p=0.004) and lower OS (HR=1.03; 95%CI: 1.02–1.05; p<0.001). Similarly, in pN2-subgroup: LNR was associated with regional-only-failure (HR=1.04; 95%CI: 1.02–1.06; p<0.001), distant-only-failure (HR=1.03; 95%CI: 1.01–1.06; p=0.045) and lower OS (HR=1.03; 95%CI: 1.02–1.04; p<0.001).ConclusionHigh LNR is associated with higher regional-only-failure/distant-only-failure and lower OS. LNR should be assessed in future prospective trials for selection of adjuvant therapy.



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Editorial Board

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Publication date: August 2017
Source:Radiotherapy and Oncology, Volume 124, Issue 2





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Contents

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Publication date: August 2017
Source:Radiotherapy and Oncology, Volume 124, Issue 2





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Two sampling strategies for an overview of pesticide contamination in an agriculture-extensive headwater stream

Abstract

Two headwaters located in southwest France were monitored for 3 and 2 years (Auvézère and Aixette watershed, respectively) with two sampling strategies: grab and passive sampling with polar organic chemical integrative sampler (POCIS). These watersheds are rural and characterized by agricultural areas with similar breeding practices, except that the Auvézère watershed contains apple production for agricultural diversification and the downstream portion of the Aixette watershed is in a peri-urban area. The agricultural activities of both are extensive, i.e., with limited supply of fertilizer and pesticides. The sampling strategies used here give specific information: grab samples for higher pesticide content and POCIS for contamination background noise and number of compounds found. Agricultural catchments in small headwater streams are characterized by a background noise of pesticide contamination in the range of 20–70 ng/L, but there may also be transient and high-peak pesticide contamination (2000–3000 ng/L) caused by rain events, poor use of pesticides, and/or the small size of the water body. This study demonstrates that between two specific runoff events, contamination was low; hence the importance of passive sampler use. While the peak pesticide concentrations seen here are a toxicity risk for aquatic life, the pesticide background noise of single compounds do not pose obvious acute nor chronic risks; however, this study did not consider the risk from synergistic "cocktail" effects. Proper tools and sampling strategies may link watershed activities (agricultural, non-agricultural) to pesticides detected in the water, and data from both grab and passive samples can contribute to discussions on environmental effects in headwaters, an area of great importance for biodiversity.



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The clinicopathologic spectrum of mature aggressive B cell lymphomas

Abstract

Our understanding of mature aggressive B cell lymphomas has evolved significantly in the last years as reflected in the 2016 update of the WHO lymphoma classification. A main topic of the 2016 European Association for Haematopathology/Society of Hematopathology lymphoma workshop in Basel therefore was the clinicopathological spectrum of mature aggressive B cell lymphomas with the exception of conventional diffuse large B cell lymphoma. In this review, we summarize two sessions dedicated to "high-grade B cell lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (so-called double/triple-hit lymphomas)" and "high-grade B cell lymphomas, NOS" as defined in the 2016 update of the WHO lymphoma classification, Burkitt lymphoma and related neoplasms, and terminally differentiated aggressive B cell lymphomas. One focus was on cases of Burkitt lymphoma with unusual clinical features such as spontaneous regression or association with immunosuppression, and the new provisional category of Burkitt-like lymphoma with 11q aberration. The large numbers of cases submitted for the new high-grade categories with or without genetic "double/triple hit" demonstrated the broad clinical and pathological spectrum of this group and gave ample opportunity for discussion. In this review, current definitions and our understanding of the main high-grade categories, potential problem areas, and suggestions for the immunophenotypic and genetic work-up of these neoplasms are discussed and illustrated by many interesting and challenging cases submitted to the workshop.



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Inside Front Cover - Editorial Board Page

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Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177





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Clinicopathologic factors associated with recurrence in parotid carcinoma

Publication date: Available online 25 August 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Dong Hoon Lee, Tae Mi Yoon, Joon Kyoo Lee, Sang Chul Lim
IntroductionParotid carcinomas have varying histological types and diverse biologic behaviors. Establishing an adequate treatment plan and predicting recurrence is important.ObjectiveTo analyze the risk factors associated with recurrence in our 5 year experience with 30 cases of primary parotid carcinoma undergoing surgery at a single institute.MethodsFrom January 2009 to December 2013, 30 patients with surgical treatment of parotid carcinoma were identified based on their medical records.ResultsThe 30 patients were comprised of 17 males and 13 females. Among 11 patients with T4 tumors, seven patients had recurrence. Among seven patients with cervical nodal metastasis, all patient except one had recurrence. Clinically late stages (stage III and IV) showed more common recurrence than early stage (stage I and II) lesions. Lymphovascular invasion was seen in 5 patients, and all patients had recurrence. Among 11 patients with extracapsular spread, 7 patients had recurrence. In 17 patients with high grade carcinomas, ten patients had recurrence. In 13 patients with low grade carcinomas, no patients experienced recurrence.ConclusionT- and N-stage, clinical stage, lymphovascular invasion, extracapsular spread, and histopathologic grade correlate significantly with recurrence in parotid carcinoma.



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The lasso technique for endoscopic suture lateralization in bilateral vocal fold immobility



http://ift.tt/2wdhyyA

3-dimensional (3D) tissue-engineered skeletal muscle for laryngeal reconstruction

Objective

There is an unmet need for tissue-engineered three-dimensional (3D) muscle constructs for laryngeal reconstruction. Functional engineered muscle could be used to repair postoncologic or traumatic defects or to medialize the vocal fold in cases of paresis/paralysis. Autologous, organized, engineered muscle that has adequate bulk integrates into host tissue and restores function currently does not exist.

Methods

Primary skeletal muscle progenitor cells (MPCs) were isolated from F344 rats. Three-dimensional muscle constructs were created by encapsulating MPCs via flow alignment in a customized collagen formulation and cultured under passive tension. Muscle-specific immunohistochemistry and confocal microscopy were used to evaluate muscle tissue differentiation. After 2 weeks of culture, muscle constructs were implanted into surgically created defects in the rat larynx. Postmortem function testing and histology was performed at 1 and 3 months.

Results

Immunohistochemistry with confocal microscopy demonstrated well-differentiated myotubes, which were well aligned and distributed throughout the engineered construct in vitro. There was evidence of restoration of normal laryngeal function at 1 month postoperative, as indicated by safe swallow (no aspiration events), weight gain, and excellent animal survival. Postmortem specimens demonstrated functional muscle contraction on ex vivo testing, and histology confirmed integration into host tissue.

Conclusion

This is the first study to demonstrate that functional, 3D tissue-engineered skeletal muscle can be developed from primary MPCs and standardized oligomeric collagen. Collectively, these findings may have tremendous clinical implications for autologous laryngeal muscle repair and reconstruction.

Level of Evidence

NA. Laryngoscope, 2017



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Rethinking the laryngopharyngeal reflux treatment algorithm: Evaluating an alternate empiric dosing regimen and considering up-front, pH-impedance, and manometry testing to minimize cost in treating suspect laryngopharyngeal reflux disease

Objectives/Hypothesis

Empiric proton pump inhibitor (PPI) trials for laryngopharyngeal reflux (LPR) are common. A majority of the patients respond to acid suppression. This work intends to evaluate once-daily, 40 mg omeprazole and once-nightly, 300 mg ranitidine (QD/QHS) dosing as an alternative regimen, and use this study's cohort to evaluate empiric regimens prescribed for LPR as compared to up-front testing with pH impedance multichannel intraluminal impedance (MII) with dual pH probes and high-resolution manometry (HRM) for potential cost minimization.

Study Design

Retrospective cohort review and cost minimization study.

Methods

A chart review identified patients diagnosed with LPR. All subjects were treated sequentially and outcomes recorded. Initial QD/QHS dosing increased after 3 months to BID if no improvement and ultimately prescribed MII and HRM if they failed BID dosing. Decision tree diagrams were constructed to determine costs of two empiric regimens and up-front MII and HRM.

Results

Ninety-seven subjects met the criteria. Responders and nonresponders to empiric therapy were identified. Seventy-two subjects (74%) responded. Forty-eight (67% of responders and 49% of all) improved with QD/QHS dosing. Forty-nine (51%) subjects escalated to BID dosing. Twenty-four subjects (33% of responders and 25% of all) improved on BID therapy. Twenty-five subjects (26%) did not respond to acid suppression. Average weighted cost was $1,897.00 per patient for up-front testing, $3,033.00 for initial BID, and $3,366.00 for initial QD/QHS.

Conclusions

An alternate QD/QHS regimen improved the majority who presented with presumed LPR. Cost estimates demonstrate that the QD/QHS regimen was more expensive than the initial BID high-dose PPI for 6 months. Overall per-patient cost appears less with up-front MII and HRM.

Level of Evidence

4. Laryngoscope, 2017



http://ift.tt/2wdlcsf

Postoperative IPTH compared with IPTH gradient as predictors of post-thyroidectomy hypocalcemia

Objectives/Hypothesis

Predicting patients' risk for hypocalcemia after thyroidectomy may allow for same-day discharge. This study was designed to compare postoperative intact parathyroid hormone (IPTH) alone with percentage change in IPTH (IPTH gradient) in predicting post-thyroidectomy hypocalcemia.

Study Design

Retrospective cohort study.

Methods

Patients undergoing total thyroidectomy by the senior author from May 2015 to May 2016 were included. Serum IPTH was measured preoperatively and 1 hour postoperatively, and IPTH gradient was calculated. Postoperative hypocalcemia was mild (≥8.0, <8.4) or severe (<8.0 and/or hypocalcemic symptoms). Postoperative IPTH and IPTH gradient were compared with hypocalcemia using logistic regression. Receiver operating characteristic analysis of IPTH measures as predictors of hypocalcemia was performed, and the area under the curve (AUC) was calculated.

Results

Overall, 119 patients were included. Forty-seven percent of the patients developed postoperative hypocalcemia, including 26 (22%) with mild and 30 (25%) with severe hypocalcemia. Thirteen patients had hypocalcemic symptoms. Median IPTH gradient and postoperative IPTH each differed significantly by category of hypocalcemia (P < .001). Higher IPTH gradient was significantly associated with odds of severe and symptomatic hypocalcemia (adjusted odds ratio [aOR]: 1.21, 95% confidence interval [CI]: 1.06-1.39 and aOR: 1.34, 95% CI: 1.05-1.71 per 10% increase), whereas lower postoperative IPTH was not (aOR: 1.27, 95% CI: 0.95-1.68 and aOR: 1.44, 95% CI: 0.90-2.31 per 10 pg/mL decrease). The AUC for predicting severe hypocalcemia was nonsignificantly higher for IPTH gradient than postoperative IPTH (AUC = 0.77 vs. 0.69, P = .10). The AUC for predicting symptomatic hypocalcemia was significantly higher for IPTH gradient (AUC = 0.75 vs. 0.72, P = .03).

Conclusions

Our results suggest that the IPTH gradient may be more useful than postoperative IPTH alone in predicting risk of post-thyroidectomy hypocalcemia.

Level of Evidence

4. Laryngoscope, 2017



http://ift.tt/2wxEUkI

Consulting Dr. Google: Quality of Online Resources About Tympanostomy Tube Placement

Objective

Tympanostomy tube (TT) placement is common in children; however, family-centeredness and utility of online information used for decision making and understanding is unknown. We evaluate the quality of leading Internet resources describing TT placement.

Study Design

Cross-sectional descriptive design.

Methods

We performed a Google (Menlo Park, CA) search for terms related to TTs. We defined quality using scaled readability measures (Flesch Reading Ease and Flesch-Kincaid Grade-Level), understandability and actionability (Patient Education Materials Assessment Tool), shared decision-making centrality (Center for Medicare and Medicaid Services informed consent guidelines), and clinical practice guideline (CPG) compatibility. Three reviewers coded each measure. Fleiss κ interrater reliability analysis was performed.

Results

Ten most frequently encountered websites were analyzed. One of 10 met national health literacy standards (mean 10th-grade level reading, median 9th, range 6–15th). All sites were understandable (mean understandability 81.9%, range 73%–92%). Most had low actionability scores (7 of 10, median 47%, mean 44.6%, range 0–80). Shared decision-making centrality was high (mean 5, range 4–6), but most did not list alternative treatment options. Although CPG compatibility was high (mean 3.4, range 1–4), many websites contained inconsistent recommendations about tube duration, follow-up, and water precautions. There was inter-rater agreement for understandability scoring (κ = 0.20; P = 0.02).

Conclusion

Internet resources about TT placement vary in quality pertaining to health literacy, principles of shared decision making, and consistency with practice guidelines. With growing emphasis on patient-/family-centered engagement in healthcare decision making, standardization of content and improved usability of educational materials for common surgical procedures in children such as tympanostomy tube placement should be a public health priority.

Level of Evidence

NA. Laryngoscope, 2017



http://ift.tt/2wdjfvN

Use of pharyngeal packs in functional endoscopic sinus surgery: A randomized controlled trial

Objective

To determine if pharyngeal packs have an effect on postoperative pain and postoperative nausea and vomiting in functional endoscopic sinus surgery (FESS).

Study Design

Forty-six patients scheduled for routine endoscopic sinus surgery were recruited into this study. The patients were randomly allocated to have or to not have pharyngeal packing prior to surgery.

Methods

The placement of pharyngeal packs during FESS is controversial. Theoretically, pharyngeal packs may prevent postoperative nausea and vomiting by preventing ingestion of blood during sinus surgery. However, prior studies have not conclusively demonstrated this to be the case in FESS. Pharyngeal packs have been associated with complications including throat pain, aspiration, and death. The objective of this randomized control trial was to determine if pharyngeal packs have an effect on postoperative throat pain, nausea, and vomiting in order to determine their importance during FESS.

Patients were blinded to intervention. Postoperatively, throat pain and nausea/vomiting scores were recorded.

Results

There was no significant difference in mean throat pain at 4 hours following surgery (P = 0.860). At 24 hours after surgery, patients without pharyngeal packing experienced more pain than those who had a throat pack placed (P = 0.002). There was no significant difference in the level of nausea at 4 hours after surgery (P = 0.315) or at 24 hours after surgery (P = 0.315).

Conclusion

We recommend against the routine use of placing pharyngeal packs during FESS.

Level of Evidence

1b. Laryngoscope, 2017



http://ift.tt/2wdBLnX

The lasso technique for endoscopic suture lateralization in bilateral vocal fold immobility



http://ift.tt/2wdhyyA

3-dimensional (3D) tissue-engineered skeletal muscle for laryngeal reconstruction

Objective

There is an unmet need for tissue-engineered three-dimensional (3D) muscle constructs for laryngeal reconstruction. Functional engineered muscle could be used to repair postoncologic or traumatic defects or to medialize the vocal fold in cases of paresis/paralysis. Autologous, organized, engineered muscle that has adequate bulk integrates into host tissue and restores function currently does not exist.

Methods

Primary skeletal muscle progenitor cells (MPCs) were isolated from F344 rats. Three-dimensional muscle constructs were created by encapsulating MPCs via flow alignment in a customized collagen formulation and cultured under passive tension. Muscle-specific immunohistochemistry and confocal microscopy were used to evaluate muscle tissue differentiation. After 2 weeks of culture, muscle constructs were implanted into surgically created defects in the rat larynx. Postmortem function testing and histology was performed at 1 and 3 months.

Results

Immunohistochemistry with confocal microscopy demonstrated well-differentiated myotubes, which were well aligned and distributed throughout the engineered construct in vitro. There was evidence of restoration of normal laryngeal function at 1 month postoperative, as indicated by safe swallow (no aspiration events), weight gain, and excellent animal survival. Postmortem specimens demonstrated functional muscle contraction on ex vivo testing, and histology confirmed integration into host tissue.

Conclusion

This is the first study to demonstrate that functional, 3D tissue-engineered skeletal muscle can be developed from primary MPCs and standardized oligomeric collagen. Collectively, these findings may have tremendous clinical implications for autologous laryngeal muscle repair and reconstruction.

Level of Evidence

NA. Laryngoscope, 2017



http://ift.tt/2wxiBMk

Rethinking the laryngopharyngeal reflux treatment algorithm: Evaluating an alternate empiric dosing regimen and considering up-front, pH-impedance, and manometry testing to minimize cost in treating suspect laryngopharyngeal reflux disease

Objectives/Hypothesis

Empiric proton pump inhibitor (PPI) trials for laryngopharyngeal reflux (LPR) are common. A majority of the patients respond to acid suppression. This work intends to evaluate once-daily, 40 mg omeprazole and once-nightly, 300 mg ranitidine (QD/QHS) dosing as an alternative regimen, and use this study's cohort to evaluate empiric regimens prescribed for LPR as compared to up-front testing with pH impedance multichannel intraluminal impedance (MII) with dual pH probes and high-resolution manometry (HRM) for potential cost minimization.

Study Design

Retrospective cohort review and cost minimization study.

Methods

A chart review identified patients diagnosed with LPR. All subjects were treated sequentially and outcomes recorded. Initial QD/QHS dosing increased after 3 months to BID if no improvement and ultimately prescribed MII and HRM if they failed BID dosing. Decision tree diagrams were constructed to determine costs of two empiric regimens and up-front MII and HRM.

Results

Ninety-seven subjects met the criteria. Responders and nonresponders to empiric therapy were identified. Seventy-two subjects (74%) responded. Forty-eight (67% of responders and 49% of all) improved with QD/QHS dosing. Forty-nine (51%) subjects escalated to BID dosing. Twenty-four subjects (33% of responders and 25% of all) improved on BID therapy. Twenty-five subjects (26%) did not respond to acid suppression. Average weighted cost was $1,897.00 per patient for up-front testing, $3,033.00 for initial BID, and $3,366.00 for initial QD/QHS.

Conclusions

An alternate QD/QHS regimen improved the majority who presented with presumed LPR. Cost estimates demonstrate that the QD/QHS regimen was more expensive than the initial BID high-dose PPI for 6 months. Overall per-patient cost appears less with up-front MII and HRM.

Level of Evidence

4. Laryngoscope, 2017



http://ift.tt/2wdlcsf

Postoperative IPTH compared with IPTH gradient as predictors of post-thyroidectomy hypocalcemia

Objectives/Hypothesis

Predicting patients' risk for hypocalcemia after thyroidectomy may allow for same-day discharge. This study was designed to compare postoperative intact parathyroid hormone (IPTH) alone with percentage change in IPTH (IPTH gradient) in predicting post-thyroidectomy hypocalcemia.

Study Design

Retrospective cohort study.

Methods

Patients undergoing total thyroidectomy by the senior author from May 2015 to May 2016 were included. Serum IPTH was measured preoperatively and 1 hour postoperatively, and IPTH gradient was calculated. Postoperative hypocalcemia was mild (≥8.0, <8.4) or severe (<8.0 and/or hypocalcemic symptoms). Postoperative IPTH and IPTH gradient were compared with hypocalcemia using logistic regression. Receiver operating characteristic analysis of IPTH measures as predictors of hypocalcemia was performed, and the area under the curve (AUC) was calculated.

Results

Overall, 119 patients were included. Forty-seven percent of the patients developed postoperative hypocalcemia, including 26 (22%) with mild and 30 (25%) with severe hypocalcemia. Thirteen patients had hypocalcemic symptoms. Median IPTH gradient and postoperative IPTH each differed significantly by category of hypocalcemia (P < .001). Higher IPTH gradient was significantly associated with odds of severe and symptomatic hypocalcemia (adjusted odds ratio [aOR]: 1.21, 95% confidence interval [CI]: 1.06-1.39 and aOR: 1.34, 95% CI: 1.05-1.71 per 10% increase), whereas lower postoperative IPTH was not (aOR: 1.27, 95% CI: 0.95-1.68 and aOR: 1.44, 95% CI: 0.90-2.31 per 10 pg/mL decrease). The AUC for predicting severe hypocalcemia was nonsignificantly higher for IPTH gradient than postoperative IPTH (AUC = 0.77 vs. 0.69, P = .10). The AUC for predicting symptomatic hypocalcemia was significantly higher for IPTH gradient (AUC = 0.75 vs. 0.72, P = .03).

Conclusions

Our results suggest that the IPTH gradient may be more useful than postoperative IPTH alone in predicting risk of post-thyroidectomy hypocalcemia.

Level of Evidence

4. Laryngoscope, 2017



http://ift.tt/2wxEUkI

Consulting Dr. Google: Quality of Online Resources About Tympanostomy Tube Placement

Objective

Tympanostomy tube (TT) placement is common in children; however, family-centeredness and utility of online information used for decision making and understanding is unknown. We evaluate the quality of leading Internet resources describing TT placement.

Study Design

Cross-sectional descriptive design.

Methods

We performed a Google (Menlo Park, CA) search for terms related to TTs. We defined quality using scaled readability measures (Flesch Reading Ease and Flesch-Kincaid Grade-Level), understandability and actionability (Patient Education Materials Assessment Tool), shared decision-making centrality (Center for Medicare and Medicaid Services informed consent guidelines), and clinical practice guideline (CPG) compatibility. Three reviewers coded each measure. Fleiss κ interrater reliability analysis was performed.

Results

Ten most frequently encountered websites were analyzed. One of 10 met national health literacy standards (mean 10th-grade level reading, median 9th, range 6–15th). All sites were understandable (mean understandability 81.9%, range 73%–92%). Most had low actionability scores (7 of 10, median 47%, mean 44.6%, range 0–80). Shared decision-making centrality was high (mean 5, range 4–6), but most did not list alternative treatment options. Although CPG compatibility was high (mean 3.4, range 1–4), many websites contained inconsistent recommendations about tube duration, follow-up, and water precautions. There was inter-rater agreement for understandability scoring (κ = 0.20; P = 0.02).

Conclusion

Internet resources about TT placement vary in quality pertaining to health literacy, principles of shared decision making, and consistency with practice guidelines. With growing emphasis on patient-/family-centered engagement in healthcare decision making, standardization of content and improved usability of educational materials for common surgical procedures in children such as tympanostomy tube placement should be a public health priority.

Level of Evidence

NA. Laryngoscope, 2017



http://ift.tt/2wdjfvN

Use of pharyngeal packs in functional endoscopic sinus surgery: A randomized controlled trial

Objective

To determine if pharyngeal packs have an effect on postoperative pain and postoperative nausea and vomiting in functional endoscopic sinus surgery (FESS).

Study Design

Forty-six patients scheduled for routine endoscopic sinus surgery were recruited into this study. The patients were randomly allocated to have or to not have pharyngeal packing prior to surgery.

Methods

The placement of pharyngeal packs during FESS is controversial. Theoretically, pharyngeal packs may prevent postoperative nausea and vomiting by preventing ingestion of blood during sinus surgery. However, prior studies have not conclusively demonstrated this to be the case in FESS. Pharyngeal packs have been associated with complications including throat pain, aspiration, and death. The objective of this randomized control trial was to determine if pharyngeal packs have an effect on postoperative throat pain, nausea, and vomiting in order to determine their importance during FESS.

Patients were blinded to intervention. Postoperatively, throat pain and nausea/vomiting scores were recorded.

Results

There was no significant difference in mean throat pain at 4 hours following surgery (P = 0.860). At 24 hours after surgery, patients without pharyngeal packing experienced more pain than those who had a throat pack placed (P = 0.002). There was no significant difference in the level of nausea at 4 hours after surgery (P = 0.315) or at 24 hours after surgery (P = 0.315).

Conclusion

We recommend against the routine use of placing pharyngeal packs during FESS.

Level of Evidence

1b. Laryngoscope, 2017



http://ift.tt/2wdBLnX

Extra-ocular movement restriction and diplopia following orbital fracture repair

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Publication date: Available online 25 August 2017
Source:American Journal of Otolaryngology
Author(s): H.A. Shah, Taha Shipchandler, Dominic Vernon, Maraya Baumanis, David Chan, William R. Nunery, Hui Bae Harold Lee
PurposeTo report a series of patients with extra-ocular movement restriction and diplopia after orbital fracture repair, and determine the effect of timing of repair and the type of implant used.MethodsA chart review was conducted identifying all patients >18years of age at our institution between June 2005 and June 2008 who underwent orbital fracture repair, and presented with clinically significant diplopia and extra-ocular movement restriction persisting longer than one month after repair. Data collected included timing of repair, implant used within the orbit, and need for revision.ResultsTen patients were identified with a mean time to primary orbital fracture repair at 9days (range 1–48). Seven patients underwent revision of their orbital fracture repair with removal of the previously placed implant and replacement with non-porous 0.4mm Supramid Foil, whereas one patient underwent lateral and inferior rectus recessions without revision of primary fracture repair. Titanium mesh was the intra-orbital implant found in all patients requiring revision of orbital fracture repair. All revisions resulted in resolution of clinically significant diplopia.ConclusionsClinically significant diplopia and extra-ocular movement restriction is not an uncommon complication after orbital fracture repair. In our series, there was a strong association between these complications and the use of porous titanium mesh implants. Revision of fractures significantly improved diplopia in all but one patient. This suggests that meticulous fracture repair and the use of non-porous implants primarily or secondarily may preclude the need for strabismus surgery after orbital trauma.



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Comment on: “The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach”

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Publication date: Available online 25 August 2017
Source:American Journal of Otolaryngology
Author(s): Zhengcai Lou




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Well-Differentiated Thyroid Cancer Neovasculature Expresses Prostate-Specific Membrane Antigen—a Possible Novel Therapeutic Target

Abstract

Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein receptor, is highly expressed in prostate cancer and in the tumor neovasculature of colon, breast, and adrenocortical tumors. Here, we analyzed PSMA expression in the neovasculature of various thyroid cancer subtypes and assessed whether PSMA expression is correlated with aggressive behavior. From a prospectively maintained database, we evaluated 91 samples from 68 patients, including 37 primary differentiated thyroid cancers (DTCs) [11 classic papillary (cPTC), 9 follicular-variant (FvPTC), 11 follicular (FTC), 6 radioactive iodine-refractory (RAIR)], 5 anaplastic (ATC) carcinomas, 9 distant and 12 lymph node metastases, 21 benign thyroid nodules, and 7 normal thyroid specimens. Formalin-fixed paraffin-embedded tissue blocks were immunostained for vascular endothelial marker CD31 and PSMA with proper controls. PSMA expression was not detected in normal thyroid tissue. DTC tumors demonstrated a significantly higher PSMA expression, in regard to both intensity and percentage of vessels stained, than benign tumors (p < 0.001). Among the histologic subtypes, cPTC, FTC, and RAIR carcinomas demonstrated the highest percent of moderate to strong PSMA staining. PSMA expression was seen more frequently in specimens from distant metastases (100%) compared with specimens from only lymph node metastases (67%). PSMA is significantly overexpressed in the neovasculature of DTCs compared with normal and benign thyroid nodules specifically with increased expression in RAIR carcinomas and distant metastases. PSMA should be further explored as a novel therapeutic target for metastatic and RAIR carcinomas.



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The molecular mechanisms of sexual orientation and gender identity

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Publication date: Available online 25 August 2017
Source:Molecular and Cellular Endocrinology
Author(s): Alessandra Fisher, Jiska Ristori, Girolamo Morelli, Mario Maggi
Differences between males and females are widely represented in nature. There are gender differences in phenotypes, personality traits, behaviors and interests, cognitive performance, and proneness to specific diseases. The most marked difference in humans is represented by sexual orientation and core gender identity, the origins of which are still controversial and far from being understood. Debates continue on whether sexual behavior and gender identity are a result of biological (nature) or cultural (nurture) factors, with biology possibly playing a major role. The main goal of this review is to summarize the studies available to date on the biological factors involved in the development of both sexual orientation and gender identity. A systematic search of published evidence was performed using Medline (from January 1948 to June 2017). Review of the relevant literature was based on authors' expertise. Indeed, different studies have documented the possible role and interaction of neuroanatomic, hormonal and genetic factors. The sexual dimorphic brain is considered the anatomical substrate of psychosexual development, on which genes and gonadal hormones may have a shaping effect. In particular, growing evidence shows that prenatal and pubertal sex hormones permanently affect human behavior. In addition, heritability studies have demonstrated a role of genetic components. However, a convincing candidate gene has not been identified. Future studies (e.i. genome wide studies) are needed to better clarify the complex interaction between genes, anatomy and hormonal influences on psychosexual development.



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