Κυριακή 6 Αυγούστου 2017
Angiogenesis, Invasion, and Metastasis Characteristics of Hepatocellular Carcinoma
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Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans
Abstract
Background
The gut hormone motilin stimulates gastrointestinal motility by inducing gastric phase III of the migrating motor complex (MMC) and enhancing the rate of gastric emptying. Camicinal (GSK962040), a small molecule motilin receptor agonist, has been shown to increase gastrointestinal motility.
Methods
In this proof of concept study the effects of camicinal on MMC activity, esophageal and gastric pH was evaluated in eight healthy volunteers as a secondary endpoint. Doses of 50 and 150 mg were compared to placebo for a period of 24 hours in a double-blinded randomized crossover trial.
Key Results
The 50 mg dose (n=4) of camicinal had no significant impact on gastroduodenal manometry or pH parameters. A single dose of 150 mg (n=4) induced a gastric phase III after 0:34 h (0:25-0:58), which was significantly faster compared to placebo (18:15 h (4:32-22:16); P=.03). Moreover, the high dose significantly increased the occurrence of gastric phase III contractions compared to placebo (12% vs 39%; P=.0003). This increase in gastric phase III contractions during a period of 24 hour was due to an increased occurrence of gastric phases III during the daytime (5% vs 50%; P=.0001). The same dose however did not affect small bowel manometry parameters or esophageal and gastric pH.
Conclusions and Inferences
Considering its stimulating effect on the MMC and gastric emptying, camicinal is an attractive candidate for the treatment of gastroparesis and gastroesophageal reflux disease. This trial was registered at clinicaltrials.gov as NCT00562848.
A high dose (150 mg) of the motilin receptor agonist, camicinal, induces premature gastric phase III contractions in healthy volunteers.
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Sleep in Patients with Chronic Migraine
Abstract
Purpose of Review
The biological and pathophysiological interaction between sleep and chronic migraine (CM) remains to be fully elucidated. In this article, we provide a narrative review of the literature on sleep disturbance and CM, highlighting recent advances in sleep research and insights into mechanisms that could mediate a role of sleep disturbances in migraine chronification. We discuss the potential for cognitive-behavioral insomnia therapy (CBTi) as an intervention for CM with comorbid insomnia. Finally, we propose a model of the mechanisms underlying the interactions among sleep physiology, maladaptive migraine-coping behaviors, and coexisting factors which contribute to sleep disturbances in CM based on conceptual models used in sleep research.
Recent Findings
Insomnia is the most common sleep complaint among patients with CM. CM patients experience more frequent and severe insomnia symptoms than patients with episodic migraine (EM). It has been suggested that sleep disturbances may predispose individuals to migraine attacks, which may affect the pain-processing trigeminovascular system and thus play a role in migraine progression. Encouraging but limited evidence suggests that management of insomnia via behavioral sleep therapy may reverse CM to EM and possibly prevent migraine chronification.
Summary
Migraine has a complex relationship with sleep. The use of objective sleep study such as polysomnographic microstructural sleep analysis and actigraphy could help connect sleep disturbances and processes related to CM. Future longitudinal studies should examine whether effective behavioral treatments such as CBTi can reverse migraine chronification.
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Sleep in Patients with Chronic Migraine
Abstract
Purpose of Review
The biological and pathophysiological interaction between sleep and chronic migraine (CM) remains to be fully elucidated. In this article, we provide a narrative review of the literature on sleep disturbance and CM, highlighting recent advances in sleep research and insights into mechanisms that could mediate a role of sleep disturbances in migraine chronification. We discuss the potential for cognitive-behavioral insomnia therapy (CBTi) as an intervention for CM with comorbid insomnia. Finally, we propose a model of the mechanisms underlying the interactions among sleep physiology, maladaptive migraine-coping behaviors, and coexisting factors which contribute to sleep disturbances in CM based on conceptual models used in sleep research.
Recent Findings
Insomnia is the most common sleep complaint among patients with CM. CM patients experience more frequent and severe insomnia symptoms than patients with episodic migraine (EM). It has been suggested that sleep disturbances may predispose individuals to migraine attacks, which may affect the pain-processing trigeminovascular system and thus play a role in migraine progression. Encouraging but limited evidence suggests that management of insomnia via behavioral sleep therapy may reverse CM to EM and possibly prevent migraine chronification.
Summary
Migraine has a complex relationship with sleep. The use of objective sleep study such as polysomnographic microstructural sleep analysis and actigraphy could help connect sleep disturbances and processes related to CM. Future longitudinal studies should examine whether effective behavioral treatments such as CBTi can reverse migraine chronification.
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Doing Mastoidectomy Along with Tympanic Membrane Repair Reduces the Need for Revision Procedures: A Prospective Study
Abstract
To determine the role of cortical mastoidectomy on the results of tympanoplsty in tubotympanic type of chronic suppurative otitis media. A prospective, observational, interventional study was conducted from a period of October 2006–October 2008. This included 40 patients of either sex in the age group of 15–45 years having tubotympanic type of CSOM. Tympanoplasty with mastoidectomy was done in all the patients and they were followed up for graft acceptance and hearing impairment for 5 years to see the long term results. Per-operatively, the antrum was involved in 17, aditus in 11 and middle ear in 8 patients. Incus was necrosed in 10 cases and malleus and incus were absent in a single case. Mucoid discharge was found in the middle ear in 12 out of 40 patients. Mucoid discharge ears had antral mucosal hypertrophy in 100%, blocked aditus in 75% and middle ear mucosal hypertrophy in 58% cases; ossicular necrosis in 75% cases. 90% of the cases had graft accepted. In dry ears, graft take up rate was 89% and in ears with mucoid discharge it was 92%. Average air–bone–gap reduced to 13.90 dB as compared to average air–bone–gap (Av. AB Gap1) preoperatively of 38.62 dB. After 5 years, 83.5% patients had >10 dB improvement in hearing. We recommend opening of the mastoid if on inspection of middle ear one finds mucoid type of discharge.
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Emerging Diagnostic and Therapeutic Strategies for Tauopathies
Abstract
Purpose of Review
Tauopathies represent a spectrum of incurable and progressive age-associated neurodegenerative diseases that currently are diagnosed definitively only at autopsy. Few clinical diagnoses, such as classic Richardson's syndrome of progressive supranuclear palsy, are specific for underlying tauopathy and no clinical syndrome is fully sensitive to reliably identify all forms of clinically manifest tauopathy. Thus, a major unmet need for the development and implementation of tau-targeted therapies is precise antemortem diagnosis. This article reviews new and emerging diagnostic therapies for tauopathies including novel imaging techniques and biomarkers and also reviews recent tau therapeutics.
Recent Findings
Building evidence from animal and cell models suggests that prion-like misfolding and propagation of pathogenic tau proteins between brain cells are central to the neurodegenerative process. These rapidly growing developments build rationale and motivation for the development of therapeutics targeting this mechanism through altering phosphorylation and other post-translational modifications of the tau protein, blocking aggregation and spread using small molecular compounds or immunotherapy and reducing or silencing expression of the MAPT tau gene.
Summary
New clinical criteria, CSF, MRI, and PET biomarkers will aid in identifying tauopathies earlier and more accurately which will aid in selection for new clinical trials which focus on a variety of agents including immunotherapy and gene silencing.
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The history and epidemiology of Middle East respiratory syndrome corona virus
Corona viruses cause common cold, and infections caused by corona viruses are generally self-resolving. During the last 4 years, corona viruses have become the most important viruses worldwide because of the o...
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Cancer survivorship and opioid prescribing rates: A population-based matched cohort study among individuals with and without a history of cancer
BACKGROUND
Little is known about opioid prescribing among individuals who have survived cancer. Our aim is to examine a predominantly socio-economically disadvantaged population for differences in opioid prescribing rates among cancer survivors compared with matched controls without a prior diagnosis of cancer.
METHODS
This was a retrospective population-wide matched cohort study. Starting in 2010, individuals residing in Ontario, Canada, who were 18 to 64 years of age and at least 5 years past their cancer diagnosis were matched to controls without a prior cancer diagnosis based on sex and calendar year of birth. Follow-up was terminated at any indication of cancer recurrence, second malignancy, or new cancer diagnosis. To examine the association between survivorship and the rate of opioid prescriptions, an Andersen-Gill recurrent event regression model was implemented, adjusting for numerous individual-level characteristics and also accounting for the matched design.
RESULTS
The rate of opioid prescribing was 1.22 times higher among survivors than among their corresponding matched controls (adjusted relative rate, 1.22; 95% CI, 1.11-1.34). Individuals from lower income quintiles who were younger, were from rural neighborhoods, and had more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates. This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis (compared with their controls).
CONCLUSION
This study demonstrates substantially higher opioid prescribing rates among cancer survivors, even long after attaining survivorship. This raises concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment. Cancer 2017. © 2017 American Cancer Society.
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Hepatic Dysfunction in Renal Cell Carcinoma: Not What You Think?
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Traditional or regenerative periodontal surgery?—a comparison of the publications between two periodontal journals over time
Abstract
Objectives
The objective is to compare the amount and content of publications regarding traditional or regenerative periodontal surgery in the years 1982/1983 and 2012/2013 in two leading periodontal journals of North America and Europe.
Material and methods
The search was carried out in the Journal of Periodontology and Journal of Clinical Periodontology. Four reviewers screened the articles and allocated the topics with respect to periodontal surgery. The distribution of articles with respect to traditional or regenerative periodontal surgery was then compared between the journals and the respective time periods.
Results
Out of 1084 screened articles, 145 articles were included. Articles with periodontal surgery content amounted to 18% for the first time period and to 11% for the second time period. In the years 1982/1983, 7% of articles in the Journal of Periodontology and 8% in the Journal of Clinical Periodontology referred to traditional periodontal surgery, while 8% (Journal of Periodontology) and 5% (Journal of Clinical Periodontology) examined regenerative periodontal surgery. The distribution changed 30 years later, with 1% (Journal of Periodontology) and 3% (Journal of Clinical Periodontology) traditional periodontal surgery and 7% and 6% regenerative periodontal surgery content.
Conclusion
While the clinical need for traditional periodontal surgery remained, research in this important field decreased. Publications rather tended to focus on adjunctive regenerative measures.
Clinical relevance
Periodontal surgery with adjunctive regenerative measures is an established and well-documented clinical procedure. However, with respect to the dominance of horizontal bone loss in periodontally diseased patients, there is a need for ongoing research with focus on traditional periodontal surgery.
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Interactions between cannabidiol and commonly used antiepileptic drugs
Summary
Objective
To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs.
Methods
In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose. AEDs with interactions seen in initial analysis were plotted for mean change in serum level over time. Subanalyses were performed to determine if the frequency of sedation in participants was related to the mean serum N-desmethylclobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate.
Results
Increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p < 0.01) serum levels were seen with increasing CBD dose. Increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) with increasing CBD dose were seen in adults. Except for clobazam and desmethylclobazam, all noted mean level changes were within the accepted therapeutic range. Sedation was more frequent with higher N-desmethylclobazam levels in adults (p = 0.02), and AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01).
Significance
Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD.
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Traditional or regenerative periodontal surgery?—a comparison of the publications between two periodontal journals over time
Abstract
Objectives
The objective is to compare the amount and content of publications regarding traditional or regenerative periodontal surgery in the years 1982/1983 and 2012/2013 in two leading periodontal journals of North America and Europe.
Material and methods
The search was carried out in the Journal of Periodontology and Journal of Clinical Periodontology. Four reviewers screened the articles and allocated the topics with respect to periodontal surgery. The distribution of articles with respect to traditional or regenerative periodontal surgery was then compared between the journals and the respective time periods.
Results
Out of 1084 screened articles, 145 articles were included. Articles with periodontal surgery content amounted to 18% for the first time period and to 11% for the second time period. In the years 1982/1983, 7% of articles in the Journal of Periodontology and 8% in the Journal of Clinical Periodontology referred to traditional periodontal surgery, while 8% (Journal of Periodontology) and 5% (Journal of Clinical Periodontology) examined regenerative periodontal surgery. The distribution changed 30 years later, with 1% (Journal of Periodontology) and 3% (Journal of Clinical Periodontology) traditional periodontal surgery and 7% and 6% regenerative periodontal surgery content.
Conclusion
While the clinical need for traditional periodontal surgery remained, research in this important field decreased. Publications rather tended to focus on adjunctive regenerative measures.
Clinical relevance
Periodontal surgery with adjunctive regenerative measures is an established and well-documented clinical procedure. However, with respect to the dominance of horizontal bone loss in periodontally diseased patients, there is a need for ongoing research with focus on traditional periodontal surgery.
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Hard tissue debris removal from the mesial root canal system of mandibular molars with ultrasonically and laser-activated irrigation: a micro-computed tomography study
Abstract
This study is to investigate the efficacy of different irrigant activation techniques on removal of accumulated hard tissue debris (AHTD) in mesial roots of human mandibular molars. Extracted human mandibular molars with an isthmus between the mesial root canals were selected based on micro-CT (μCT) scans. The mesial canals were instrumented to an apical diameter ISO30 using ProTaper rotary files. Teeth were randomly assigned to three irrigant activation groups (n = 10): ultrasonically activated irrigation (UAI) using a size 20 Irrisafe for 3 × 20 s, laser-activated irrigation (LAI) with an Er:YAG laser (2940 nm) and plain 300 μm fiber tip inside the canal (20 mJ, 20 Hz, 3 × 20 s), and laser-activated irrigation with identical parameters with a 400 μm photon-induced photoacoustic streaming (PIPS) tip held at the canal entrance. All teeth were scanned with μCT before and after instrumentation and after irrigant activation. After reconstruction and image processing, the canal system volume filled with hard tissue debris before and after irrigant activation was calculated. Changes in hard tissue debris volumes were compared between groups using one-way ANOVA. The percentage volume of hard tissue debris (vol%) was significantly lower after irrigant activation in all groups. Although the lowest debris values were observed in the laser groups, no significant differences in the vol% of accumulated hard tissue debris after activation were observed between groups. Accumulated hard tissue debris was reduced significantly in all activation groups. Ultrasonically and laser-activated irrigation regimens performed similarly in this respect. None of the tested methods was able to render the root canal systems free of debris.
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A preliminary investigation of short-term cytokine expression in gingival crevicular fluid secondary to high-level orthodontic forces and the associated root resorption: case series analytical study
Orthodontically induced iatrogenic root resorption (OIIRR) is an unavoidable inflammatory process. Several factors claimed to be related to the severity of OIIRR. Orthodontic forces cause micro-trauma to the p...
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A survey of epilepsy knowledge, attitudes and practice in school-aged children in Bangkok, Thailand
Objectives
To estimate the level of knowledge about epilepsy, attitude towards PWE and practice in school-aged children in Bangkok, Thailand. Significant findings from this study will be employed to develop a relevant and effective tool to educate children.
Materials and Methods
This cross-sectional survey study was conducted in Bangkok, Thailand, from August 2014 to December 2015. Study population included school-aged children between 9 and 14 years (4th to 8th grade). A structured age-appropriate, Thai culture-adjusted and simple 20-item questionnaire was used for this survey. The questionnaire comprised three domains which were eight items for knowledge (K), seven items for attitudes (A), and five items for practice (P). Descriptive and analytic statistics including Pearson's correlation were used to find correlation among KAP domains and age with KAP scores.
Results
A total of 1040 students from 13 schools participated in our survey study. Mean age was 11.27 (SD 0.94). Some basic knowledge about epilepsy and practice of inserting objects into mouth of seizing persons account for a high magnitude of misunderstanding. Girls and older-aged children are associated with better positive attitudes towards epilepsy. It seems that educating children with knowledge of both epilepsy and first aid is necessary to improve positive attitudes among this age group.
Conclusions
Given the findings, our study suggests that a lack of knowledge in some aspects of KAP in children exists. Educational materials should contain basic knowledge about the simple pathogenesis of seizure, seizure types and seizure characteristics, and provide explanation as to why inserting objects into mouths of seizing persons is not recommended.
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Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing
Summary
Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.
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A Rare Case of Cutaneous Plasmacytosis in a Korean Male
Cutaneous and systemic plasmacytosis are reactive disease processes that occur in middle-aged Japanese and Chinese men. Systemic plasmacytosis, defined by plasmacytic infiltration of two organ systems, might rarely progress to lymphoma. Cutaneous plasmacytosis, however, is chronic and benign and is characterized by the development of multiple plasma cell-rich infiltrates in the skin. We present a case of cutaneous plasmacytosis in a 46-year-old Korean male. The patient demonstrated classic features of the disease entity, including disseminated red-brown plaques, differentiated plasmacytoid infiltrates on biopsy, hypergammaglobulinemia, and the absence of systemic disease.
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Endoscopic Treatment of Sphenoid Sinus Mucocele: Case Report and Surgical Considerations
Introduction. The paranasal sinuses mucoceles are benign expansive cystic lesions that occur rarely in the sphenoid sinus and contain mucous material enclosed by cylindrical pseudostratified epithelium. Objective. To report one case of sphenoid sinus mucocele that occurred with headache and was submitted to surgical treatment through endonasal endoscopy approach. Case Report. 59-year-old male patient with history of increasing frontoorbital, bilateral, fluctuating headache and exophthalmos. There was no other associated clinical abnormality. Computed Tomography (CT) and Magnetic Resonance Image (MRI) scans confirmed an expansive mass of sphenoid sinus, suggesting mucocele. The patient was submitted to endonasal endoscopic surgery with posterior ethmoidotomy, large sphenoidotomy, and marsupialization of the lesion. Conclusion. Mucoceles of the sphenoid sinus are a very rare condition with variable clinical and radiological presentation. Surgical treatment is absolutely indicated and early treatment avoids visual damage that can be permanent. Endonasal endoscopic approach with drainage and marsupialization of sphenoid sinus, using a transnasal corridor, is a safe and effective treatment modality.
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Comparison of intravoxel incoherent motion diffusion-weighted imaging between turbo spin-echo and echo-planar imaging of the head and neck.
| Related Articles |
Comparison of intravoxel incoherent motion diffusion-weighted imaging between turbo spin-echo and echo-planar imaging of the head and neck.
Eur Radiol. 2017 Aug 04;:
Authors: Mikayama R, Yabuuchi H, Sonoda S, Kobayashi K, Nagatomo K, Kimura M, Kawanami S, Kamitani T, Kumazawa S, Honda H
Abstract
OBJECTIVES: To compare image quality, apparent diffusion coefficient (ADC), and intravoxel incoherent motion (IVIM)-derived parameters between turbo spin-echo (TSE)-diffusion-weighted imaging (DWI) and echo-planar imaging (EPI)-DWI of the head and neck.
METHODS: Fourteen volunteers underwent head and neck imaging using TSE-DWI and EPI-DWI. Distortion ratio (DR), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), ADC and IVIM-derived parameters were compared between the two techniques. Bland-Altman analysis was performed to analyse reproducibility between the quantitative parameters of TSE-DWI and EPI-DWI.
RESULTS: DR of TSE-DWI was significantly smaller than that of EPI-DWI. SNR and CNR of TSE-DWI were significantly higher than those of EPI-DWI. ADC and IVIM-derived parameters of TSE-DWI showed higher values than those of EPI-DWI, although the difference was not significant. Bland-Altman analysis showed wide limits of agreement between the two sequences.
CONCLUSION: TSE-DWI can produce better image quality than EPI-DWI, while TSE-DWI possibly exhibits different values of quantitative parameters. Therefore, TSE-DWI could be a good alternative to EPI-DWI for patients sensitive to distortion. However, it is not recommended to use both TSE-DWI and EPI-DWI on follow-up.
KEY POINTS: • Head and neck DWI is especially sensitive to magnetic inhomogeneity. • The distortion of images was less with TSE-DWI than with EPI-DWI. • TSE-DWI can possibly exhibit higher ADC and IVIM-derived parameters than EPI-DWI. • Bland-Altman analysis showed unacceptable LoA in quantitative analysis between TSE-DWI and EPI-DWI. • It is not recommended to use both TSE-DWI and EPI-DWI for follow-up.
PMID: 28779394 [PubMed - as supplied by publisher]
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Endoscopic Treatment of Sphenoid Sinus Mucocele: Case Report and Surgical Considerations
Introduction. The paranasal sinuses mucoceles are benign expansive cystic lesions that occur rarely in the sphenoid sinus and contain mucous material enclosed by cylindrical pseudostratified epithelium. Objective. To report one case of sphenoid sinus mucocele that occurred with headache and was submitted to surgical treatment through endonasal endoscopy approach. Case Report. 59-year-old male patient with history of increasing frontoorbital, bilateral, fluctuating headache and exophthalmos. There was no other associated clinical abnormality. Computed Tomography (CT) and Magnetic Resonance Image (MRI) scans confirmed an expansive mass of sphenoid sinus, suggesting mucocele. The patient was submitted to endonasal endoscopic surgery with posterior ethmoidotomy, large sphenoidotomy, and marsupialization of the lesion. Conclusion. Mucoceles of the sphenoid sinus are a very rare condition with variable clinical and radiological presentation. Surgical treatment is absolutely indicated and early treatment avoids visual damage that can be permanent. Endonasal endoscopic approach with drainage and marsupialization of sphenoid sinus, using a transnasal corridor, is a safe and effective treatment modality.
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National Breast Reconstruction Utilization in the Setting of Postmastectomy Radiotherapy: Two-Stage Implant-Based Breast Reconstruction
J reconstr Microsurg
DOI: 10.1055/s-0037-1604389
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Full text
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Improved middle-ear soft-tissue visualization using synchrotron radiation phase-contrast imaging
Source:Hearing Research
Author(s): Mai Elfarnawany, Seyed Alireza Rohani, Soroush Ghomashchi, Daniel G. Allen, Ning Zhu, Sumit K. Agrawal, Hanif M. Ladak
High resolution images are used as a basis for finite-element modeling of the middle-ear structures to study their biomechanical function. Commonly used imaging techniques such as micro-computed tomography (CT) and optical microscopy require extensive sample preparation, processing or staining using contrast agents to achieve sufficient soft-tissue contrast. We compare imaging of middle-ear structures in unstained, non-decalcified human temporal bones using conventional absorption-contrast micro-CT and using synchrotron radiation phase-contrast imaging (SR-PCI). Four cadaveric temporal bones were imaged using SR-PCI and conventional micro-CT. Images were qualitatively compared in terms of visualization of structural details and soft-tissue contrast using intensity profiles and histograms. In order to quantitatively compare SR-PCI to micro-CT, three-dimensional (3D) models of the ossicles were constructed from both modalities using a semi-automatic segmentation method as these structures are clearly visible in both types of images. Volumes of the segmented ossicles were computed and compared between the two imaging modalities and to estimates from the literature. SR-PCI images provided superior visualization of soft-tissue microstructures over conventional micro-CT images. Intensity profiles emphasized the improved contrast and detectability of soft-tissue in SR-PCI in comparison to absorption-contrast micro-CT. In addition, the semi-automatic segmentations of SR-PCI images yielded accurate 3D reconstructions of the ossicles with mean volumes in accord with volume estimates from micro-CT images and literature. Sample segmentations of the ossicles and soft tissue structures were provided on an online data repository for benefit of the research community. The improved visualization, modeling accuracy and simple sample preparation make SR-PCI a promising tool for generating reliable FE models of the middle-ear structures, including both soft tissues and bone.
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Proteome profiling of s-nitrosylated synaptosomal proteins by isobaric mass tags
Publication date: Available online 5 August 2017
Source:Journal of Neuroscience Methods
Author(s): Teodora Stella Wijasa, Marc Sylvester, Nahal Brocke-Ahmadinejad, Markus P. Kummer, Frederic Brosseron, Volkmar Gieselmann, Michael T. Heneka
Graphical abstract
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High content analysis of phagocytic activity and cell morphology with PuntoMorph
Source:Journal of Neuroscience Methods
Author(s): Hassan Al-Ali, Han Gao, Camilla Dalby-Hansen, Vanessa Ann Peters, Yan Shi, Roberta Brambilla
BackgroundPhagocytosis is essential for maintenance of normal homeostasis and healthy tissue. As such, it is a therapeutic target for a wide range of clinical applications. The development of phenotypic screens targeting phagocytosis has lagged behind, however, due to the difficulties associated with image-based quantification of phagocytic activity.New methodWe present a robust algorithm and cell-based assay system for high content analysis of phagocytic activity. The method utilizes fluorescently labeled beads as a phagocytic substrate with defined physical properties. The algorithm employs statistical modeling to determine the mean fluorescence of individual beads within each image, and uses the information to conduct an accurate count of phagocytosed beads. In addition, the algorithm conducts detailed and sophisticated analysis of cellular morphology, making it a standalone tool for high content screening.ResultsWe tested our assay system using microglial cultures. Our results recapitulated previous findings on the effects of microglial stimulation on cell morphology and phagocytic activity. Moreover, our cell-level analysis revealed that the two phenotypes associated with microglial activation, specifically cell body hypertrophy and increased phagocytic activity, are not highly correlated. This novel finding suggests the two phenotypes may be under the control of distinct signaling pathways.Comparison with existing methodsWe demonstrate that our assay system outperforms preexisting methods for quantifying phagocytic activity in multiple dimensions including speed, accuracy, and resolution.ConclusionsWe provide a framework to facilitate the development of high content assays suitable for drug screening. For convenience, we implemented our algorithm in a standalone software package, PuntoMorph.
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Functional overestimation due to spatial smoothing of fMRI data
Publication date: Available online 5 August 2017
Source:Journal of Neuroscience Methods
Author(s): Peng Liu, Vince Calhoun, Zikuan Chen
BackgroundPearson correlation (simply correlation) is a basic technique for neuroimage function analysis. It has been observed that the spatial smoothing may cause functional overestimation, which however remains a lack of complete understanding. Herein, we present a theoretical explanation from the perspective of correlation scale invariance.New MethodsFor a task-evoked spatiotemporal functional dataset, we can extract the functional spatial map by calculating the temporal correlations (tcorr) of voxel timecourses against the task timecourse. From the relationship between image noise level (changed through spatial smoothing) and the tcorr map calculation, we show that the spatial smoothing causes a noise reduction, which in turn smooths the tcorr map and leads to a spatial expansion on neuroactivity blob estimation.ResultsThrough numerical simulations and subject experiments, we show that the spatial smoothing of fMRI data may overestimate activation spots in the correlation functional map. Our results suggest a small spatial smoothing (with a smoothing kernel with a full width at half maximum (FWHM) of no more than two voxels) on fMRI data processing for correlation-based functional mappingComparison with existing methodsIn extreme noiselessness, the correlation of scale-invariance property defines a meaningless binary tcorr map. In reality, a functional activity blob in a tcorr map is shaped due to the spoilage of image noise on correlative responses. We may reduce data noise level by smoothing processing, which poses a smoothing effect on correlation. This logic allows us to understand the noise dependence and the smoothing effect of correlation-based fMRI data analysis.
Graphical abstract
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A comparison of weekly paclitaxel and cetuximab with the EXTREME regimen in the treatment of recurrent/metastatic squamous cell head and neck carcinoma
Source:Oral Oncology, Volume 73
Author(s): Kenji Nakano, Shoko Marshall, Shinichiro Taira, Yukiko Sato, Junichi Tomomatsu, Toru Sasaki, Wataru Shimbashi, Hirofumi Fukushima, Hiroyuki Yonekawa, Hiroki Mitani, Kazuyoshi Kawabata, Shunji Takahashi
BackgroundThe effectiveness of the combination chemotherapy of weekly paclitaxel and cetuximab has not yet been compared to that of the current standard regimen, EXTREME (combination of 5-fluorouracil, cisplatin and cetuximab).MethodsWe retrospectively reviewed the clinical records of R/M SCCHN patients who received cetuximab-containing chemotherapy as a first-line therapy; from these, patients receiving a weekly paclitaxel and cetuximab regimen (cohort A) and the EXTREME regimen (cohort B) were extracted. The responses, prognoses and adverse events of these two cohorts were evaluated.ResultsA total of 86 patients were included (cohort A, 49; cohort B, 36). Patients with histories of platinum-based chemotherapy were more frequently given the cohort A treatment. Though the response rates were similar in the two cohorts (45% in cohort A and 51% in cohort B; p=0.83), the progression-free survival (PFS) was significantly more favorable in cohort A by the log-rank test (6.0monthsvs 5.0months; p=0.027). In the Cox-regression hazard analyses, male gender (hazard ratio [HR]=2.1, p=0.010), older age (≥ 70 yo) (HR=5.0, p=0.018), PS 0 (HR=2.2, p=0.027), no history of platinum chemotherapy (HR=3.2, p=0.003) and the presence of a tracheostomy (HR=2.3, p=0.039) were favorable factors within cohort A.ConclusionIn selected R/M SCCHN patients, the combination of weekly paclitaxel and cetuximab could be the better treatment option than the EXTREME regimen.
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The difficult management of radio-incuced head and neck sarcomas
Source:Oral Oncology
Author(s): Valentina Terenzi, Andrea Cassoni, Marco Della Monaca, Giulia Di Benedetto, Paolo Priore, Andrea Battisti, Valentino Valentini
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Improved middle-ear soft-tissue visualization using synchrotron radiation phase-contrast imaging
Publication date: Available online 5 August 2017
Source:Hearing Research
Author(s): Mai Elfarnawany, Seyed Alireza Rohani, Soroush Ghomashchi, Daniel G. Allen, Ning Zhu, Sumit K. Agrawal, Hanif M. Ladak
High resolution images are used as a basis for finite-element modeling of the middle-ear structures to study their biomechanical function. Commonly used imaging techniques such as micro-computed tomography (CT) and optical microscopy require extensive sample preparation, processing or staining using contrast agents to achieve sufficient soft-tissue contrast. We compare imaging of middle-ear structures in unstained, non-decalcified human temporal bones using conventional absorption-contrast micro-CT and using synchrotron radiation phase-contrast imaging (SR-PCI). Four cadaveric temporal bones were imaged using SR-PCI and conventional micro-CT. Images were qualitatively compared in terms of visualization of structural details and soft-tissue contrast using intensity profiles and histograms. In order to quantitatively compare SR-PCI to micro-CT, three-dimensional (3D) models of the ossicles were constructed from both modalities using a semi-automatic segmentation method as these structures are clearly visible in both types of images. Volumes of the segmented ossicles were computed and compared between the two imaging modalities and to estimates from the literature. SR-PCI images provided superior visualization of soft-tissue microstructures over conventional micro-CT images. Intensity profiles emphasized the improved contrast and detectability of soft-tissue in SR-PCI in comparison to absorption-contrast micro-CT. In addition, the semi-automatic segmentations of SR-PCI images yielded accurate 3D reconstructions of the ossicles with mean volumes in accord with volume estimates from micro-CT images and literature. Sample segmentations of the ossicles and soft tissue structures were provided on an online data repository for benefit of the research community. The improved visualization, modeling accuracy and simple sample preparation make SR-PCI a promising tool for generating reliable FE models of the middle-ear structures, including both soft tissues and bone.
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New Recommendations of the IFCN: from scalp EEG to electrical brain imaging
Source:Clinical Neurophysiology
Author(s): Louis Maillard, Georgia Ramantani
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Idiopathic intracranial hypertension: ocular vestibular evoked myogenic potentials as a new evaluation tool
Source:Clinical Neurophysiology
Author(s): Robert Gürkov, Luis Wittwer, Guillaume Speierer, René Müri, Georgios Mantokoudis, Roger Kalla
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A smoking-related background helps moderate smokers to focus: An Event-Related Potential study using a Go-NoGo Task
Source:Clinical Neurophysiology
Author(s): Sandrine Detandt, Ariane Bazan, Elisa Schröder, Giulia Olyff, Hendrik Kajosch, Paul Verbanck, Salvatore Campanella
ObjectiveCognitive impairment is a major component in addiction. However, research has been inconclusive as to whether this is also the case for smokers. The present study aims at providing electrophysiological clue for altered inhibitory control in smokers and at investigating whether reduced inhibition was more pronounced during exposure to a smoking cue.MethodsERPs were recorded during a visual Go-NoGo task performed by 18 smokers and 23 controls, in which either a frequent Go signal (letter "M") or a rare No-Go signal ("letter W") were superimposed on three different long-lasting background contexts: black-neutral, smoking-related and non smoking-related.Results1) Smokers performed worse and had an earlier NoGo-N2 latency as compared to controls and independently of context, suggesting a general inhibition impairment; 2) With smoking-related backgrounds specifically, smokers made fewer mistakes than they did in other contexts and displayed a larger NoGo P3 amplitude.ConclusionThese data might suggest that background cues related to addiction may help smokers to be more accurate in an inhibition task.SignificanceOur results show the classical inhibitory impairment in smokers as compared to non-smokers. However, our data also suggest that a smoking-related background may bolster the inhibitory ability of smokers specifically.
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Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes
Source:European Journal of Cancer, Volume 84
Author(s): Sebastian Stintzing, Sabine Tejpar, Peter Gibbs, Lars Thiebach, Heinz-Josef Lenz
Metastatic colorectal carcinoma (mCRC) is a heterogeneous disease with differing outcomes and clinical responses and poor prognosis. CRCs can be characterised by their primary tumour location within the colon. The left-sided colon, derived from the hindgut, includes the distal third of the transverse colon, splenic flexure, descending colon, sigmoid colon and rectum. The right-sided colon, derived from the midgut, includes the proximal two-thirds of the transverse colon, ascending colon and caecum. Sometimes, the rectum is described separately, despite originating from the hindgut, and in many clinical series, the left-sided colon includes only tumours within and distal to the splenic flexure. Differences in the microbiome, clinical characteristics and chromosomal and molecular characteristics have been reported between the right and left side of the colon, regardless of how this is defined. There is now strong evidence from clinical studies in patients with mCRC for the prognostic effect of primary tumour location. The impact of primary colonic tumour location on response to treatment is now under investigation in a large number of clinical studies in patients with mCRC.In this review, we summarise the microbiome, clinical, chromosomal and molecular differences associated with the primary location of CRC. We present an overview of the proven prognostic impact of primary tumour location for patients with mCRC and discuss emerging data for the predictive impact of primary tumour location on clinical outcome.
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Editorial Board
Source:Dental Materials, Volume 33, Issue 9
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Aging of 3Y-TZP dental zirconia and yttrium depletion
Source:Dental Materials
Author(s): P. Pandoleon, E. Kontonasaki, N. Kantiranis, N. Pliatsikas, P. Patsalas, L. Papadopoulou, T. Zorba, K.M. Paraskevopoulos, P. Koidis
ObjectiveYttrium-stabilized zirconia is susceptible to low temperature degradation after interaction with water. Various mechanisms by which water molecules destabilize the tetragonal phase have been proposed, while the concept of yttrium depletion by the incorporation of hydroxyl ions in the crystalline structure either through the formation of YOH/ZrOH bonds or small α-Y(OH)3 crystallites, is prevailing. The present study was performed to investigate the surface alterations on a 3Y-TZP dental ceramic during the process of in-vitro aging and to further explore the yttrium depletion mechanism that occurs upon interaction with water.MethodsSurface structural changes of zirconia specimens where investigated before and after in-vitro aging with X-ray diffraction analysis, Fourier-transformed infrared spectroscopy, X-ray photoelectron spectroscopy, fluorescence microscopy and scanning electron microscopy.ResultsHigh luminescence generated from the non-aged specimen was explained by the high amount of oxygen vacancies. The phase transformation from the t-ZrO2 to the m-ZrO2 phase after aging was accompanied by a significant loss of yttrium, a clear decrease of oxygen vacancies and a profound decrease of luminescence. Surface oxygen vacancies either migrated into the inner of the specimens or/and/engaged oxygen from the ZrO2 and formed the metallic phase of Y2O3 on the surface after aging.SignificanceAn "ideal" amount of oxygen vacancies that could stabilize the tetragonal phase in Y-TZP zirconia ceramics, without compromising esthetics and LTD resistance, is still a matter of further research and different susceptibilities to LTD among various dental zirconia ceramics are based on the amount of oxygen vacancies that can be annihilated by water molecules.
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European Society for Swallowing Disorders FEES Accreditation Program for Neurogenic and Geriatric Oropharyngeal Dysphagia.
| Related Articles |
European Society for Swallowing Disorders FEES Accreditation Program for Neurogenic and Geriatric Oropharyngeal Dysphagia.
Dysphagia. 2017 Aug 04;:
Authors: Dziewas R, Baijens L, Schindler A, Verin E, Michou E, Clave P, European Society for Swallowing Disorders
PMID: 28779300 [PubMed - as supplied by publisher]
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European Society for Swallowing Disorders FEES Accreditation Program for Neurogenic and Geriatric Oropharyngeal Dysphagia.
| Related Articles |
European Society for Swallowing Disorders FEES Accreditation Program for Neurogenic and Geriatric Oropharyngeal Dysphagia.
Dysphagia. 2017 Aug 04;:
Authors: Dziewas R, Baijens L, Schindler A, Verin E, Michou E, Clave P, European Society for Swallowing Disorders
PMID: 28779300 [PubMed - as supplied by publisher]
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Botulinum Toxin Injections Into the Lateral Cricoarytenoid Muscles for Vocal Process Granuloma.
| Related Articles |
Botulinum Toxin Injections Into the Lateral Cricoarytenoid Muscles for Vocal Process Granuloma.
J Voice. 2017 Aug 01;:
Authors: Pham Q, Campbell R, Mattioni J, Sataloff R
Abstract
OBJECTIVE: Contact granulomas are benign, exophytic inflammatory lesions of the larynx that typically arise on or near the vocal process of the arytenoid cartilage. The most common management options include voice therapy and antireflux pharmacotherapy, intralesional steroid injections, botulinum toxin injections, and surgical excision. In-office Botox injection into the lateral cricoarytenoid (LCA) muscle can be effective even for recurrent granulomas.
STUDY DESIGN: This is a retrospective chart review and literature review.
METHOD: We reviewed more than 400 charts and included two patients, who underwent in-office injection with botulinum toxin A into LCA muscles bilaterally, after previously failing both conservative and surgical management.
RESULTS: Both cases showed significant improvement of the laryngeal granulomas after 6 months and a single botulinum toxin injection. Both cases were initially grade III granuloma that improved to grade I.
CONCLUSIONS: In-office injection of botulinum toxin A targeting the LCA muscle appears to be a safe and effective treatment modality in refractory laryngeal granuloma.
PMID: 28778373 [PubMed - as supplied by publisher]
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In reference to "The transotic approach for vestibular schwannoma: indications and results".
| Related Articles |
In reference to "The transotic approach for vestibular schwannoma: indications and results".
Eur Arch Otorhinolaryngol. 2017 Aug 04;:
Authors: Manoharan KS, Thakar A, Sharma SC
PMID: 28779420 [PubMed - as supplied by publisher]
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[External multicentric validation of two scores predicting the risk of relapse in patients with borderline ovarian tumors: The nomogram of Bendifallah and the score of Ouldamer].
| Related Articles |
[External multicentric validation of two scores predicting the risk of relapse in patients with borderline ovarian tumors: The nomogram of Bendifallah and the score of Ouldamer].
Bull Cancer. 2017 Aug 01;:
Authors: Pais P, Huchon C, Chevrot A, Cohen J, Fauconnier A, Rouzier R, Mimouni M
Abstract
BACKGROUND: Borderline ovarian tumors are rare and can occur in young women. For these patients, a fertility sparing surgery should be discussed. Two predicting borderline ovarian tumor relapse risk models were developed in 2014 (Nomogram of Bendifallah) and 2017 (Score of Ouldamer). This study aimed to valid in an external population, these two scores using a multi-institutional BOT database.
METHODS: In this bicentric and retrospective study, all consecutive patients comprising the variable nomogram documented treated between January 2006 and December 2012 for BOT in centre hospitalier de Poissy-Saint-Germain and hôpital René-Huguenin were included. A ROC model was established for each predicting scores.
RESULTS: Sixty-five patients were included in the study. Twelve patients showed a recurrence (19%), three of them experienced an infiltrative cancer (5%). The median time of recurrence was 25 months (range: 8-115). The concordance index for the Nomogram of Bendifallah and the Score of Ouldamer were 0.88 (IC 95% [0.78-0.98]) and 0.87 (IC 95% [0.77-0.96]) respectively.
CONCLUSION: This study from an independent population valids the Bendifallah nomogram and Ouldamer score for clinical use in predicting borderline ovarian recurrence.
PMID: 28778341 [PubMed - as supplied by publisher]
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[Lenalidomide desensitization in a patient with 5q- syndrome].
| Related Articles |
[Lenalidomide desensitization in a patient with 5q- syndrome].
Bull Cancer. 2017 Aug 01;:
Authors: Boudin L, Patient M, Roméo E, Bladé JS, de Jauréguiberry JP
PMID: 28778340 [PubMed - as supplied by publisher]
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[Pharmacist involvement in supporting care in patients receiving oral anticancer therapies: A situation report in French cancer centers].
| Related Articles |
[Pharmacist involvement in supporting care in patients receiving oral anticancer therapies: A situation report in French cancer centers].
Bull Cancer. 2017 Aug 01;:
Authors: Occhipinti S, Petit-Jean E, Pinguet F, Beaupin C, Daouphars M, Parent D, Donamaria C, Bertrand C, Divanon F, Benard-Thiery I, Chevrier R
Abstract
INTRODUCTION: The increasing prescription of oral anticancer therapies has significantly changed inpatient care to outpatient care. This transformation requires an excellent coordination between different professionals to ensure healthcare channel security.
METHOD: We performed a prospective study in 18 French cancer centers from March to April 2016. The aim of this study was to identify resources deployed to support patients receiving oral anticancer therapies and to assess pharmacist's involvement.
RESULTS: More than half of the centers have developed patient education program and/or practice pharmaceutical consultations. In total, 54.5% have deployed an oral anticancer drugs program and the pharmacist is involved in multidisciplinary teams. In total, 44.4% of the centers have developed hospital-to-community coordination actions but all of them highlight the time-consuming character of those programs.
DISCUSSION: Administrative burdens are seriously hindering patient education program's development. Multidisciplinary consultations can offer an attractive alternative because of easy implementation modalities. Finally, hospital-to-community coordination actions seem hard to implement and require harmonization of communication practices, and need more technical and financial means.
PMID: 28778339 [PubMed - as supplied by publisher]
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[Critical remarks on the new diagnostic criteria for Menière's disease].
| Related Articles |
[Critical remarks on the new diagnostic criteria for Menière's disease].
HNO. 2017 Aug 04;:
Authors: Westhofen M
PMID: 28779287 [PubMed - as supplied by publisher]
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Large and giant pituitary adenoma resection by microscopic trans-sphenoidal surgery: Surgical outcomes and complications in 123 consecutive patients.
| Related Articles |
Large and giant pituitary adenoma resection by microscopic trans-sphenoidal surgery: Surgical outcomes and complications in 123 consecutive patients.
J Clin Neurosci. 2017 Aug 01;:
Authors: Karki M, Sun J, Yadav CP, Zhao B
Abstract
To evaluate surgical outcomes and complications of patients who underwent microscopic trans-sphenoidal surgery (MTS) for large and giant pituitary adenomas (PAs). A retrospective study of electively operated cases of PA over a six year period was performed. Surgical outcomes and complications of 64 patients with large PAs (≥3cm) and 59 patients with giant PAs (>4cm), who underwent MTS at same period, were reviewed. Medical reports of all selected patients were assessed to collect demographic information such as age, sex, clinical symptoms, PA size, the extent of PA extension and resection, outcomes and complications. Patients with large PAs had improvement in visual improvement (78.1%; 50/64), gross total resection (84.4%; 54/64) compared to patients with giant PAs who had improvement in visual (71.2%; 42/59) and gross total resection (74.6%; 44/59). The rate of CSF leakage was 7.8% and 23.7% for large and giant PAs (p=0.0399). After a mean follow-up period of 40.8 (6-75) months, 10 (15.6%) patients with large PAs experienced tumor recurrence, while 2 giant PA patients (3.4%) experienced tumor recurrence after a mean follow-up period of 40.6 (3-70) months (p=0.0314). Resection of both large and giant pituitary adenomas by microscopic trans-sphenoidal surgery may be safe and effective surgical technique with low morbidity and mortality.
PMID: 28778803 [PubMed - as supplied by publisher]
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Re: ASTRO consensus guideline for oropharyngeal cancer
Source:Practical Radiation Oncology
Author(s): Gary V. Walker, Pierre Blanchard, Adam S. Garden
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Response to ASTRO consensus guideline for oropharyngeal cancer
Source:Practical Radiation Oncology
Author(s): David J. Sher, David J. Adelstein, Gopal K. Bajaj, David M. Brizel, Ezra E. Cohen, Aditya Halthore, Louis B. Harrison, Charles Lu, Benjamin J. Moeller, Harry Quon, James W. Rocco, Erich M. Sturgis, Roy B. Tishler, Andy Trotti, John Waldron, Avraham Eisbruch
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The Technology of Processed Electroencephalogram Monitoring Devices for Assessment of Depth of Anesthesia.
Commercial brain function monitors for depth of anesthesia have been available for more than 2 decades; there are currently more than 10 devices on the market. Advances in this field are evidenced by updated versions of existing monitors, development of new monitors, and increasing research unveiling the mechanisms of anesthesia on the brain. Electroencephalography signal processing forms an integral part of the technology supporting the brain function monitors for derivation of a depth-of-anesthesia index. This article aims to provide a better understanding of the technology and functionality behind these monitors. This review will highlight the general design principles of these devices and the crucial stages in electroencephalography signal processing and classification, with a focus on the key mathematical techniques used in algorithm development for final derivation of the index representing anesthetic state. We will briefly discuss the advantages and limitations of this technology in the clinical setting as a tool in our repertoire used for optimizing individualized patient care. Also included is a table describing 10 available commercial depth-of-anesthesia monitors. (C) 2017 International Anesthesia Research Society
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Atlas of Peripheral Regional Anesthesia Anatomy and Techniques, 3rd edition.
Perioperative Drill-Based Crisis Management.
Reduction in Operating Room Plasma Waste After Evidence-Based Quality Improvement Initiative.
Anesthesiologists request units of plasma in anticipation of transfusion. The amount of plasma transfused intraoperatively is less than that issued (requested, thawed, and sent). We presented institutional-specific data on plasma usage including anesthesiologist-specific ratios of plasma issued-to-transfused. In month-to-month comparisons from the year before the presentation (June-December 2015) to 7 months after (June-December 2016), plasma issued to the operating room was reduced from 434.9 +/- 81 to 327.3 +/- 65 units, a change of 107.6 units per month (95% confidence interval [CI], 22-193); plasma discarded by the blood bank was reduced from 109.7 +/- 48 units to 69.1 +/- 9 units, a change of 40.6 units per month (95% CI, 0.2-81); and plasma transfused went from 188.4 +/- 42 units to 160.7 +/- 52 units, a nonsignificant change of 27.7 units per month (95% CI, -27 to 83). (C) 2017 International Anesthesia Research Society
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An Appraisal of the Carlisle-Stouffer-Fisher Method for Assessing Study Data Integrity and Fraud.
Data fabrication and scientific misconduct have been recently uncovered in the anesthesia literature, partly via the work of John Carlisle. In a recent article in Anaesthesia, Carlisle analyzed 5087 randomized clinical trials from anesthesia and general medicine journals from 2000 to 2015. He concluded that in about 6% of studies, data comparing randomized groups on baseline variables, before the given intervention, were either too similar or dissimilar compared to that expected by usual sampling variability under the null hypothesis. Carlisle used the Stouffer-Fisher method of combining P values in Table 1 (the conventional table reporting baseline patient characteristics) for each study, then calculated trial P values and assessed whether they followed a uniform distribution across studies. Extreme P values targeted studies as likely to contain data fabrication or errors. In this Statistical Grand Rounds article, we explain Carlisle's methods, highlight perceived limitations of the proposed approach, and offer recommendations. Our main findings are (1) independence was assumed between variables in a study, which is often false and would lead to "false positive" findings; (2) an "unusual" result from a trial cannot easily be concluded to represent fraud; (3) utilized cutoff values for determining extreme P values were arbitrary; (4) trials were analyzed as if simple randomization was used, introducing bias; (5) not all P values can be accurately generated from summary statistics in a Table 1, sometimes giving incorrect conclusions; (6) small numbers of P values to assess outlier status within studies is not reliable; (7) utilized method to assess deviations from expected distributions may stack the deck; (8) P values across trials assumed to be independent; (9) P value variability not accounted for; and (10) more detailed methods needed to understand exactly what was done. It is not yet known to what extent these concerns affect the accuracy of Carlisle's results. We recommend that Carlisle's methods be improved before widespread use (applying them to every manuscript submitted for publication). Furthermore, lack of data integrity and fraud should ideally be assessed using multiple simultaneous statistical methods to yield more confident results. More sophisticated methods are needed for nonrandomized trials, randomized trial data reported beyond Table 1, and combating growing fraudster sophistication. We encourage all authors to more carefully scrutinize their own reporting. Finally, we believe that reporting of suspected data fraud and integrity issues should be done more discretely and directly by the involved journal to protect honest authors from the stigma of being associated with potential fraud. (C) 2017 International Anesthesia Research Society
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Mortality, Geriatric, and Nongeriatric Surgical Risk Factors Among the Eldest Old: A Prospective Observational Study.
BACKGROUND: Preoperative risk and postoperative outcomes among the elderly are the subject of extensive debate. However, the eldest old, that is, the fastest-growing and most vulnerable group, are insufficiently studied; even their mortality rate is unclear. This prospective observational study was performed with the aim of determining the mortality rate of this population and establishing which preoperative conditions were predictors of which postoperative outcomes. The study was undertaken between 2011 and 2015 in a major tertiary care university hospital. METHODS: All patients aged >=85 years undergoing any elective procedure during the study period were included. Patients were followed up for 30 days postoperatively. The preoperative conditions studied were demographic data, grade of surgical complexity (1-3), preoperative comorbidities, and some characteristically geriatric conditions (functional reserve, nutrition, cognitive status, polypharmacy, dependency, and frailty). The outcome measures were 30-day all-cause mortality (primary end point), morbidity, prolonged length of stay, and escalation of care in living conditions. RESULTS: Of 139 eligible patients, 127 completed follow-up. The 30-day mortality was 7.9%; 95% confidence interval (CI), 3.2-12.6. It had 3 predictors: malnutrition (odds ratio [OR], 15; 95% CI, 3-89), complexity 3 (OR, 9.1; CI, 2-52), and osteoporosis/osteoporotic fractures (OR, 14.7; CI, 2-126). Significant predictors for morbidity (40%) were ischemic heart disease (OR, 3.9; CI, 1-11) and complexity 3 (OR, 3.6; CI, 2-9), while a nonfrail phenotype (OR, 0.3; CI, 0.1-0.8) was found to be protective. Only 2 factors were found to be predictive of longer admissions, namely complexity 3 (OR, 4.4; CI, 2-10) and frailty (OR, 2.7; CI, 2-7). Finally, risk factors for escalation of care in living conditions were slow gait (a surrogate for frailty, OR, 2.5; CI, 1-6), complexity 3 (OR, 3.2; CI, 1-7), and hypertension (OR, 2.9; CI, 1-9). CONCLUSIONS: The eldest old is a distinct group with a considerable mortality rate and their own particular risk factors. Surgical complexity and certain geriatric variables (malnutrition and frailty), which are overlooked in American Society of Anesthesiologists and most other usual scores, are particularly relevant in this population. Inclusion of these factors along with appropriate comorbidities for risk stratification should guide better decision making for families and doctors alike and encourage preoperative optimization of patients. (C) 2017 International Anesthesia Research Society
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Perioperative Considerations for the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes.
Do advanced glycation end-products cause food allergy?.
Purpose of review: The aim of this study was to appraise the evidence relating to dietary advanced glycation end-products (AGEs), their influence on innate and adaptive immune responses and their possible role in the increasing rate of food allergy that is being observed globally. Recent findings: The western pattern of diet is high in both AGEs and their substrates and this has been increasing in the last 30 years. AGEs mimic alarmins such as S100 proteins and the high molecular group box 1 (HMBG1), binding to the Receptor for Advanced Glycation End Products (RAGE), which in turn influences innate and adaptive immune responses. AGEs can directly cause mast cell activation and degranulation. Population data from USA and Australia have correlates with the rise in food allergy and sources of AGEs in the diet and this is also reinforced by urban and regional data within countries. The function of the RAGE receptor is inter-twined with Toll-like receptor (TLR) signalling and vitamin D levels. Activation of the RAGE receptor results in loss of epithelial integrity. Animal models studies have shown that dietary compounds that reduce the formation of AGEs can protect from the development of food allergies; however, this has not been shown in humans. Summary: Dietary sources of AGEs and their substrates are a plausible contributor to the increasing prevalence of food allergy, which requires prospective evaluation in human populations. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Component resolved diagnostics for hymenoptera venom allergy.
Purpose of review: Component-resolved diagnostics makes use of defined allergen molecules to analyse IgE-mediated sensitizations at a molecular level. Here, we review recent studies on the use of component-resolved diagnostics in the field of Hymenoptera venom allergy (HVA) and discuss its benefits and limitations. Recent findings: Component resolution in HVA has moved from single molecules to panels of allergens. Detection of specific immunoglobulin E (sigE) to marker and cross-reactive venom allergens has been reported to facilitate the discrimination between primary sensitization and cross-reactivity and thus, to provide a better rationale for prescribing venom immunotherapy (VIT), particularly in patients sensitized to both honeybee and vespid venom. Characterization of IgE reactivity to a broad panel of venom allergens has allowed the identification of different sensitization profiles that in honeybee venom allergy were associated with increased risks for side effects or treatment failure of VIT. In contrast, component resolution so far has failed to provide reliable markers for the discrimination of sensitizations to venoms of different members of Vespidae. Summary: Component-resolved diagnostics allows a better understanding of the complexity of sensitization and cross-reactivities in HVA. In addition, the enhanced resolution and precision may allow identification of biomarkers, which can be used for risk stratification in VIT. Knowledge about the molecular composition of different therapeutic preparations may enable the selection of appropriate preparations for VIT according to individual sensitization profiles, an approach consistent with the goals of personalized medicine. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Focused Cardiac Ultrasound for the Regional Anesthesiologist and Pain Specialist.
This article in our point-of-care ultrasound (PoCUS) series discusses the benefits of focused cardiac ultrasound (FoCUS) for the regional anesthesiologist and pain specialist. Focused cardiac US is an important tool for all anesthesiologists assessing patients with critical conditions such as shock and cardiac arrest. However, given that ultrasound-guided regional anesthesia is emerging as the new standard of care, there is an expanding role for ultrasound in the perioperative setting for regional anesthesiologists to help improve patient assessment and management. In addition to providing valuable insight into cardiac physiology (preload, afterload, and myocardial contractility), FoCUS can also be used either to assess patients at risk of complications related to regional anesthetic technique or to improve management of patients undergoing regional anesthesia care. Preoperatively, FoCUS can be used to assess patients for significant valvular disease, such as severe aortic stenosis or derangements in volume status before induction of neuraxial anesthesia. Intraoperatively, FoCUS can help differentiate among complications related to regional anesthesia, including high spinal or local anesthetic toxicity resulting in hemodynamic instability or cardiac arrest. Postoperatively, FoCUS can help diagnose and manage common yet life-threatening complications such as pulmonary embolism or derangements in volume status. In this article, we introduce to the regional anesthesiologist interested in learning FoCUS the basic views (subcostal 4-chamber, subcostal inferior vena cava, parasternal short axis, parasternal long axis, and apical 4-chamber), as well as the relevant sonoanatomy. We will also use the I-AIM (Indication, Acquisition, Interpretation, and Medical decision making) framework to describe the clinical circumstances where FoCUS can help identify and manage obvious pathology relevant to the regional anesthesiologist and pain specialist, specifically severe aortic stenosis, hypovolemia, local anesthetic systemic toxicity, and massive pulmonary embolism. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.
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Immunohistochemical Differentiation of Plasmacytoid Urothelial Carcinoma From Secondary Carcinoma Involvement of the Bladder.
Plasmacytoid urothelial carcinoma (UC) is a rare variant of UC that can histologically mimic metastatic cancer involving the urinary bladder. A total of 45 cases of plasmacytoid UC were collected and reviewed histologically. The following immunohistochemical markers were performed: CDX2; polyclonal carcinoembryonic antigen (p-CEA); gross cystic disease fluid protein 15 (GCDFP-15); mammaglobin; estrogen receptor (ER); progesterone receptor (PR); GATA 3 and uroplakin II. In all cases, the plasmacytoid variant of UC lacked expression of ER and mammaglobin. In contrast, GCPDFP-15, PR, CDX2 and p-CEA showed positive staining in 11 (24.4%), 6 (13.3%), 8 (17.7%), and 22 (48.8%) cases, respectively. GCPDFP-15 was expressed in 4/8 female cases with 1 concurrently focally (+2) expressing PR. GATA 3 and uroplakin II was positive in 37/45 cases (82.2%) and 15/45 (33.3%) cases, respectively. A tissue microarray with 40 cases of infiltrating lobular carcinoma of the breast was stained for uroplakin II, and was negative in all cases. Tissue microarrays with 46 cases of gastric signet ring cell adenocarcinomas were all negative for GCDFP-15, ER, PR, GATA3, uroplakin II, and mammaglobin. A panel of stains including mammaglobin, ER, and uroplakin II is recommended to exclude metastatic lobular breast carcinoma to the bladder in cases where a conventional UC component is not present. Immunohistochemistry for CDX2 and p-CEA cannot be utilized to differentiate signet ring cell adenocarcinoma of the gastrointestinal tract from plasmacytoid UC; GATA3 or uroplakin II immunoreactivity can rule out a gastric primary given their negativity in signet ring cell adenocarcinoma of the stomach. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2wwci7O
Differentiating Posttransplant Inflammatory Bowel Disease and Other Colitides in Renal Transplant Patients.
Renal transplant recipients who present with gastrointestinal complaints may have symptoms related to their underlying renal disease or secondary to their immunosuppressive regimen. Immunosuppression increases patients' risk for infection and medication-induced injury, and a subset of transplant patients develop a form of inflammatory bowel disease (IBD) despite being immunosuppressed. In this study, we present the spectrum of changes in colonic biopsy histology that occur in the postrenal transplant population, with emphasis on the clinical and histologic features that may allow distinction between several common disorders. Over a 15-year period, 51 postrenal transplant patients underwent colonoscopy with biopsy. Eleven (22%) patients had infectious colitis, and 10 of these had biopsy proven acute colitis. Another 17 (33%) patients were determined to have a medication-related injury based on resolution of symptoms following drug cessation. The majority (53%) of these colonic biopsies demonstrated crypt epithelial cell apoptosis and/or architectural distortion, although 41% were histologically normal. Four (8%) patients were ultimately diagnosed with a form of IBD after exclusion of other etiologies; biopsies from these patients demonstrated chronic active colitis or enteritis with plasma cell-rich expansion of the lamina propria and basal lymphoplasmacytosis. The increased prevalence of IBD in this patient cohort (4/700) compared with that reported in the overall North American population (1 to 2/700) is in line with prior studies and is likely related to the therapeutic regimen and associated immune dysregulation that occurs in solid-organ transplant recipients. We demonstrate that a combination of clinical, endoscopic, and histologic features are useful to distinguish among causes of gastrointestinal symptoms in this high risk population. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Criteria for Risk Stratification of Vulvar and Vaginal Smooth Muscle Tumors: An Evaluation of 71 Cases Comparing Proposed Classification Systems.
Accurate risk stratification of smooth muscle tumors (SMTs) is essential for appropriate patient management. Yet, the rarity of SMTs of the vagina and vulva makes development of a prognostically meaningful classification system challenging. While 2 classification methods for vulvar SMTs and 1 for vaginal SMTs have been proposed, it is our experience that many pathologists tend to apply criteria for uterine SMTs when evaluating vulvovaginal tumors. We retrospectively reviewed a large cohort of vulvovaginal SMTs with clinical follow-up and evaluated which method most accurately classified tumors according to patient outcome. A total of 71 tumors, 53 vaginal (75%) and 18 vulvar (25%), from 71 patients were identified. All tumors were centrally examined for degree of cytologic atypia, morphology (spindled, epithelioid, myxoid), mitotic index per 10 high power fields, atypical mitotic figures, tumor cell necrosis, ischemic necrosis, tumor interface (circumscribed or infiltrative) and margin status. Clinical features were recorded for each patient. Follow-up was available for 63 patients (89%), and ranged from 1 to 234 months (median: 64 mo). While site-specific and uterine criteria showed equally excellent sensitivity in classifying smooth muscle neoplasms as leiomyosarcoma according to patient outcome, uterine criteria showed improved specificity relatively to site-specific methods in classifying tumors as nonsarcoma according to patient outcome. We recommend that uterine SMT criteria and nomenclature be adopted for evaluation and classification of vulvovaginal SMTs. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC): Further Morphologic and Molecular Characterization of ESC RCC as a Distinct Entity.
Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) has been recently described as a unique and indolent renal neoplasm, found in female patients with and without tuberous sclerosis complex. Although ESC RCC has a distinct morphology and frequent CK20 reactivity, its molecular karyotype has been previously studied only in few cases. We identified 19 ESC RCC from multiple institutions; all patients were female individuals without clinical features of tuberous sclerosis complex. Molecular karyotyping was performed in 13 cases (12 with informative result). The median age was 55 years (range: 32 to 79 y). The tumors were yellow-gray with a median size of 31 mm (range: 12 to 135 mm) and showed solid and cystic gross appearance. All tumors demonstrated typical microscopic features with solid areas admixed with variably sized macrocysts and microcysts. The cells showed eosinophilic cytoplasm with granular cytoplasmic stippling and round-to-oval nuclei. CK20 was positive in 14/19 (74%) cases. Stage pT1 was found in 17/19 (89%) patients (pT1a in 12, pT1b in 5); 1 patient each had pT2a and pT3a. A total of 15/16 patients with available follow-up were alive and without evidence of disease progression, after 1 to 169 months (median: 44 mo; mean: 49.6 mo); 3 died of other causes. The most common copy number gains were 16p13.3-16q23.1 (33% to 67%), 7p21.2-7q36.2 (42% to 50%), 13q14.2 (33%), and 19p12 (33%). The most common copy number losses included Xp11.21 (42%) and 22q11.23 (33%). Loss of heterozygosity was most frequently found at 16p11.2-11.1 (75%), Xq11.1-13.1 (75%), Xq13.1-21.1 (33%), 11p11.2-11.11 (33%), 9q21.1-22.2 (33%), and 9q33.1 (33%). ESC RCC demonstrates common molecular karyotype alterations, which further support its distinct nature. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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