Exploratory study of atmospheric methane enhancements derived from natural gas use in the Houston urban area

Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Nancy P. Sanchez, Chuantao Zheng, Weilin Ye, Beata Czader, Daniel S. Cohan, Frank K. Tittel, Robert J. Griffin
The extensive use of natural gas (NG) in urban areas for heating and cooking and as a vehicular fuel is associated with potentially significant emissions of methane (CH4) to the atmosphere. Methane, a potent greenhouse gas that influences the chemistry of the atmosphere, can be emitted from different sources including leakage from NG infrastructure, transportation activities, end-use uncombusted NG, landfills and livestock. Although significant CH4 leakage associated with aging local NG distribution systems in the U.S. has been reported, further investigation is required to study the role of this infrastructure component and other NG-related sources in atmospheric CH4 enhancements in urban centers. In this study, neighborhood-scale mobile-based monitoring of potential CH4 emissions associated with NG in the Greater Houston area (GHA) is reported. A novel dual-gas 3.337 μm interband cascade laser-based sensor system was developed and mobile-mode deployed for simultaneous CH4 and ethane (C2H6) monitoring during a period of over 14 days, corresponding to ∼ 90 h of effective data collection during summer 2016. The sampling campaign covered ∼250 exclusive road miles and was primarily concentrated on eight residential zones with distinct infrastructure age and NG usage levels. A moderate number of elevated CH4 concentration events (37 episodes) with mixing ratios not exceeding 3.60 ppmv and associated with atmospheric background enhancements below 1.21 ppmv were observed during the field campaign. Source discrimination analyses based on the covariance between CH4 and C2H6 levels indicated the predominance of thermogenic sources (e.g., NG) in the elevated CH4 concentration episodes. The volumetric fraction of C2H6 in the sources associated with the thermogenic CH4 spikes varied between 2.7 and 5.9%, concurring with the C2H6 content in NG distributed in the GHA. Isolated CH4 peak events with significantly higher C2H6 enhancements (∼11%) were observed at industrial areas and locations with high density of petroleum and gas pipelines in the GHA, indicating potential variability in Houston's thermogenic CH4 sources.



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Detection of nuclear testing from surface concentration measurements: Analysis of radioxenon from the February 2013 underground test in North Korea

Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): R.J. Kurzeja, R.L. Buckley, D.W. Werth, S.R. Chiswell
A method is outlined and tested to detect low level nuclear or chemical sources from time series of concentration measurements. The method uses a mesoscale atmospheric model to simulate the concentration signature from a known or suspected source at a receptor which is then regressed successively against segments of the measurement series to create time series of metrics that measure the goodness of fit between the signatures and the measurement segments. The method was applied to radioxenon data from the Comprehensive Test Ban Treaty (CTBT) collection site in Ussuriysk, Russia (RN58) after the Democratic People's Republic of Korea (North Korea) underground nuclear test on February 12, 2013 near Punggye. The metrics were found to be a good screening tool to locate data segments with a strong likelihood of origin from Punggye, especially when multiplied together to a determine the joint probability. Metrics from RN58 were also used to find the probability that activity measured in February and April of 2013 originated from the Feb 12 test. A detailed analysis of an RN58 data segment from April 3/4, 2013 was also carried out for a grid of source locations around Punggye and identified Punggye as the most likely point of origin. Thus, the results support the strong possibility that radioxenon was emitted from the test site at various times in April and was detected intermittently at RN58, depending on the wind direction. The method does not locate unsuspected sources, but instead, evaluates the probability of a source at a specified location. However, it can be extended to include a set of suspected sources. Extension of the method to higher resolution data sets, arbitrary sampling, and time-varying sources is discussed along with a path to evaluate uncertainty in the calculated probabilities.



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Transcription factor EB (TFEB) influences invasion and migration in oral squamous cell carcinomas

Abstract

Objective

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and plays an important role in various cancers. However, the function of TFEB in oral squamous cell carcinomas has not been examined. The aim of this study was to elucidate the role of TFEB in oral squamous cell carcinomas.

Materials and Methods

Expression levels of TFEB were examined in six different human oral squamous carcinoma cells: HSC2, HSC3, HSC4, SAS, OSC20, and SCC25. Knockdown of TFEB using small interfering RNA in HSC2 and HSC4 cells was performed. Cell morphology was observed by immunofluorescence microscopy. Cell proliferation, invasion, and adhesion were analysed.

Results

Expression levels of TFEB were high in HSC2, moderate in HSC4 and SCC25, and low in HSC3 and OSC20 cells. Knockdown of TFEB did not affect proliferation of HSC2 and HSC4 cells, but did induced enlargement of lysosomes and endosomes in HSC4 cells. TFEB silencing reduced invasion and migration of these HSC cell squamous carcinoma cells; however, increased cell adhesion was also observed.

Conclusions

TFEB knockdown reduces invasion and migration of cancer cells, likely through lysosomal regulation. Taken together, TFEB influences cell invasion and migration of oral squamous cell carcinomas.

This article is protected by copyright. All rights reserved.

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Diagnostic accuracy of level IV portable sleep monitors versus polysomnography for obstructive sleep apnea: a systematic review and meta-analysis

Abstract

Purpose

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. In-laboratory, overnight type I polysomnography (PSG) is the current "gold standard" for diagnosing OSA. Home sleep apnea testing (HSAT) using portable monitors (PMs) is an alternative testing method offering better comfort and lower costs. We aimed to systematically review the evidence on diagnostic ability of type IV PMs compared to PSG in diagnosing OSA.

Methods

Participants: patients ≥16 years old with symptoms suggestive of OSA;intervention: type IV PMs (devices with < 2 respiratory channels); comparator: in-laboratory PSG; outcomes: diagnostic accuracy measures;studies: cross-sectional, prospective observational/experimental/quasi-experimental studies; information sources: MEDLINE and Cochrane Library from January 1, 2010 to May 10, 2016. All stages of review were conducted independently by two investigators.

Results

We screened 6054 abstracts and 117 full-text articles to select 24 full-text articles for final review. These 24 studies enrolled a total of 2068 patients with suspected OSA and evaluated 10 different PMs with one to six channels. Only seven (29%) studies tested PMs in the home setting. The mean difference (bias) between PSG-measured and PM-measured apnea-hypopnea index (AHI) ranged from − 14.8 to 10.6 events/h. At AHI ≥ 5 events/h, the sensitivity of type IV PMs ranged from 67.5–100% and specificity ranged from 25 to 100%.

Conclusion

While current evidence is not very strong for the stand-alone use of level IV PMs in clinical practice, they can potentially widen access to diagnosis and treatment of OSA. Policy recommendations regarding HSAT use should also consider the health and broader social implications of false positive and false negative diagnoses.

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MiR-29 silencing modulates the expression of target genes related to proliferation, apoptosis and methylation in Burkitt lymphoma cells

Abstract

Purpose

Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis.

Methods

Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression. BL cells were treated with 5-aza-2′-deoxycytidine (decitabine) and evaluated for miR29 expressions and methylation status. DNMT3B inhibition was performed by DNMT3B siRNA.

Results

Ectopic expression of miR-29s in BL cells decreased CDK6, DNMT3B, TCL1 and MCL-1 protein levels, but CDK6 and MCL-1 mRNA expression was unaffected by miR-29. Decitabine enhanced miR-29 expression levels and decreased CDK6 protein expression. Additionally, inhibition of DNMT3B by siRNA increased miR-29a/b expression. Notably, the miR-29a/b1 and miR-29b2/c promoter genes showed methylated CpG sequences that were demethylated after decitabine treatments. Furthermore, MYC-negative tumours had higher levels of miR-29 expression compared with MYC-translocated cases, suggesting that MYC regulates miR-29 in BL tumours.

Conclusions

Our results suggest a significant role for miR-29s in BL pathogenesis in altering the expression of targets involved in critical cancer pathways, such as cell cycle control, apoptosis inhibition and DNA methylation. Moreover, methylation-mediated miR-29 epigenetic silencing may occur during BL development.

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Is insufficient pulmonary air support the cause of dysphonia in chronic obstructive pulmonary disease?

Publication date: Available online 8 January 2018
Source:Auris Nasus Larynx
Author(s): Megahed M. Hassan, Mona T. Hussein, Ahmed Mamdouh Emam, Usama M. Rashad, Ibrahim Rezk, Al Hussein Awad
ObjectiveOptimal pulmonary air support is essential pre-requisite for efficient phonation. The objective is to correlate pulmonary and vocal functions in chronic obstructive pulmonary disease (COPD) to find out whether the reduced pulmonary function per se could induce dysphonia.MethodsIn this prospective case-control study, sixty subjects with stable COPD underwent evaluation of pulmonary and vocal functions. The pulmonary functions measured include {Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF)}. The vocal functions were {jitter, shimmer, noise-to-harmonic ratio, pitch perturbation quotient, amplitude perturbation quotient, maximum phonation time (MPT), sound pressure level, phonatory efficiency, resistance and power. A control group (n=35) underwent the same measurements. These functions were compared between subjects and controls. Also, correlation of the vocal and pulmonary functions was conducted.ResultsThirty five (58.3%) of COPD subjects have dysphonia. The pulmonary functions were lower in all COPD group than in the control group (P<0.001 for all parameters). Also, the FVC, FEV1, PEF and MMEF % of predicted values were significantly lower in subjects with dysphonia (n=35) than those without dysphonia (n=25) with P values 0.0018, <0.001, 0.0011 and 0.0026 respectively. In addition, the MPT in all subjects showed positive correlations to the 5 pulmonary functions (P=0.004 for FEV1/FVC ratio and P<0.001 for the rest). Also, the phonatory efficiency showed significant positive correlations with the pulmonary functions FVC, FEV1, PEF and MMEF (P=0.001, 0.001, 0.002 and 0.001 respectively). Unlike efficiency, the phonatory resistance revealed significant negative correlations with these pulmonary functions in the same order (P=0.001, 0.003, 0.002, 0.001 respectively).ConclusionDysphonia is a common comorbidity with COPD which attributed to multifactorial etiologies. The lower the pulmonary function in COPD patients is the more likely to have dysphonia. Decreased pulmonary function was associated with reduced MPT and phonatory efficiency but with increased phonatory resistance. The reduced pulmonary functions in COPD can be the underlying cause of the altered vocal function and dysphonia. Great part of this dysphonia is functional, and hence, can be corrected by voice therapy in compensated subjects. Further researches are needed to evaluate the efficacy of voice therapy in these patients.



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Diagnostic accuracy of level IV portable sleep monitors versus polysomnography for obstructive sleep apnea: a systematic review and meta-analysis

Abstract

Purpose

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. In-laboratory, overnight type I polysomnography (PSG) is the current "gold standard" for diagnosing OSA. Home sleep apnea testing (HSAT) using portable monitors (PMs) is an alternative testing method offering better comfort and lower costs. We aimed to systematically review the evidence on diagnostic ability of type IV PMs compared to PSG in diagnosing OSA.

Methods

Participants: patients ≥16 years old with symptoms suggestive of OSA;intervention: type IV PMs (devices with < 2 respiratory channels); comparator: in-laboratory PSG; outcomes: diagnostic accuracy measures;studies: cross-sectional, prospective observational/experimental/quasi-experimental studies; information sources: MEDLINE and Cochrane Library from January 1, 2010 to May 10, 2016. All stages of review were conducted independently by two investigators.

Results

We screened 6054 abstracts and 117 full-text articles to select 24 full-text articles for final review. These 24 studies enrolled a total of 2068 patients with suspected OSA and evaluated 10 different PMs with one to six channels. Only seven (29%) studies tested PMs in the home setting. The mean difference (bias) between PSG-measured and PM-measured apnea-hypopnea index (AHI) ranged from − 14.8 to 10.6 events/h. At AHI ≥ 5 events/h, the sensitivity of type IV PMs ranged from 67.5–100% and specificity ranged from 25 to 100%.

Conclusion

While current evidence is not very strong for the stand-alone use of level IV PMs in clinical practice, they can potentially widen access to diagnosis and treatment of OSA. Policy recommendations regarding HSAT use should also consider the health and broader social implications of false positive and false negative diagnoses.

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Volumetric comparison of maxillofacial soft tissue morphology: CT in the supine position versus three-dimensional optical scanning in the sitting position

Publication date: Available online 8 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Yoshihiro Yamaguchi, Kensuke Yamauchi, Hikari Suzuki, Yuko Sai, Shinnosuke Nogami, Tetsu Takahashi
ObjectiveThree-dimensional (3D) surgical simulation has become popular, but the accuracy of such simulation is difficult to assess. Because maxillofacial soft tissue profiles vary with posture, we compared such profiles obtained in the supine and sitting positions.Study DesignIn total, 28 patients with skeletal class III jaw deformities underwent computed tomography (CT) in the supine position and 3D optical scanning in the sitting position. The two sets of 3D data were superimposed, and linear and volumetric differences were calculated. We evaluated the cheeks, the subauricular and infraorbital regions, the nose, the lips, and the chin. Statistical analyses were performed using paired Student's t-tests. Differences with P < 0.05 were considered to be significant.ResultsPatients were divided into three groups based on body mass index (BMI). The facial profiles of the cheeks and subauricular areas differed significantly between the sitting and supine positions. The extent of variation increased with BMI.ConclusionsWhen a patient moves from a sitting to a supine position, maxillofacial soft tissue migrates from the cheeks to the subauricular regions. Thus, simulations for surgery based on supine CT alone do not accurately model the cheeks and subauricular areas.



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Informed refusal in oral and maxillofacial radiology: does it exist?

Publication date: Available online 8 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): James R. Geist




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Exogenous Cushing syndrome due to misuse of potent topical steroid

Abstract

We report an infant with exogenous Cushing syndrome after being treated for 2 months with a potent topical corticosteroid via the mother's application of topical clobetasol for diaper rash without a prescription. We emphasize that potent topical steroids should be used with great caution, especially when used under occlusion (e.g., diaper area) and that parents should be warned about potential side effects of these medications, particularly when used in infants.

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Doing the math: A simple approach to topical timolol dosing for infantile hemangiomas

Abstract

Topical timolol maleate has recently gained popularity as a treatment for superficial infantile hemangiomas, but calculating a safe dose of timolol can be time consuming, which may limit the medication's use in fast-paced clinical environments. This report offers a simplified calculation of the maximum daily safe dosage as 1 drop of medication per kilogram of body weight.

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Mood changes with methotrexate therapy for dermatologic disease

Abstract

Neurotoxicity and cognitive effects of low-dose methotrexate for rheumatologic disease have often been described, but the neuropsychiatric effects of low-dose methotrexate for cutaneous disease have been underreported in the dermatology literature. We describe two children who experienced mood changes with methotrexate treatment for lichen sclerosus with morphea overlap and psoriasis, with rapid resolution of these symptoms after methotrexate cessation. We also detail possible mechanisms underlying psychiatric changes with methotrexate therapy.

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Pityriasis lichenoides: Long-term follow-up study

Abstract

Background/Objectives

Pityriasis lichenoides is an uncommon papulosquamous disorder of unknown etiology. The objective of this study was to review the clinical features and treatment responses of individuals with pityriasis lichenoides seen at a tertiary referral center.

Methods

Seventy-five patients diagnosed with pityriasis lichenoides between 1997 and 2013 were reviewed, and 46 had long-term follow-up via telephone interviews.

Results

Fifty (67%) patients were diagnosed with pityriasis lichenoides chronica, 22 (29%) with pityriasis lichenoides et varioliformis acuta, and 3 (4%) with mixed pityriasis lichenoides chronica and pityriasis lichenoides et varioliformis acuta features. Mean ± standard deviation age at onset was 12 ± 13 years (median 8 years). Disease duration was significantly shorter for patients with pityriasis lichenoides et varioliformis acuta (35 ± 35 months) than for those with pityriasis lichenoides chronica (at least 78 ± 48 months). At long-term follow-up, 23 of 28 (82%) patients with pityriasis lichenoides chronica and 3 of 16 (19%) with pityriasis lichenoides et varioliformis acuta had active disease. None progressed to lymphomatoid papulosis or cutaneous T-cell lymphoma. Ten of 23 active pityriasis lichenoides chronica cases had residual pigmentary change independent of race and lasted at least 35 ± 20 months. The most effective treatments were phototherapy (47% response rate), heliotherapy (33%), topical corticosteroids (27%), and antibiotics (25%).

Conclusion

Pityriasis lichenoides is a predominantly pediatric disorder. The time course of pityriasis lichenoides chronica is significantly longer than that of pityriasis lichenoides et varioliformis acuta. Pityriasis lichenoides chronica may persist with pigmentary alterations in the absence of other signs of active inflammation. Treatment response is often limited, particularly for patients with pityriasis lichenoides chronica.

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Treatment Outcomes of Bilateral Medialization Thyroplasty for Presbylaryngis

Publication date: Available online 8 January 2018
Source:Journal of Voice
Author(s): Jordan J. Allensworth, Karla O'Dell, Aaron Ziegler, Linda Bryans, Paul Flint, Joshua Schindler
BackgroundPresbylaryngis is a common cause of dysphonia in elderly patients. Type I thyroplasty serves to improve glottic closure and vocal quality by correcting bowing. Although unilateral and injection-based procedures are well-characterized in the treatment of broadly defined glottic insufficiency, there are insufficient outcomes data for bilateral medialization thyroplasty in the treatment of presbylaryngis. The aim of this study was to review the change in measures of vocal quality before and after bilateral medialization thyroplasty for presbylaryngis.Study DesignThis is a retrospective case series.MethodsThe records of 21 patients with presbylaryngis undergoing bilateral medialization thyroplasty between 2007 and 2014 were reviewed. Implant materials included silastic (n = 17) and hydroxyapatite (n = 4). Preoperative and postoperative comparison of vocal function was conducted using Voice Handicap Index, maximum phonation time, auditory-perceptual severity ratings, and blinded paired-comparison of Consensus Auditory-Perceptual Evaluation of Voice and Visual-perceptual stroboscopic ratings. Paired sample t tests were used to assess all outcome measures.ResultsSignificant improvements were found in Voice Handicap Index scores (P < 0.007), maximum phonation time (P < 0.03), Consensus Auditory-Perceptual Evaluation of Voice (P < 0.04), and clinician rating of vocal quality (P < 0.0001). Blinded raters noted a significant improvement in audio (P < 0.05) and videostroboscopic (P < 0.003) samples after surgery. There were no operative complications observed, and median hospital stay was one night.ConclusionsPatients with presbylaryngis demonstrated significant improvement in both objective and subjective measures of vocal quality following bilateral medialization thyroplasty. These data suggest that medialization thyroplasty is a safe option that warrants consideration in the treatment of presbylaryngis.



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How Age and Frequency Impact the Thyroid Cartilages of Professional Singers

Publication date: Available online 8 January 2018
Source:Journal of Voice
Author(s): Fabian Unteregger, Jan Thommen, Flurin Honegger, Silke Potthast, Salome Zwicky, Claudio Storck
Objectives/HypothesisYoung professional singers can easily reach very high pitches. In contrast, older singers often complain that they have to exert substantially more laryngopharyngeal force to reach the same high pitch compared with their earlier years. Various factors such as the property changes of the mucosa and ossification that impact the singing apparatus were suggested as explanations in the literature. The aim of this study was to analyze thyroid deformation—and thereby stiffness indirectly—during singing as a potential reason for this phenomenon.Study DesignProspective study.Methods/designWe examined 44 female professional singers. High-resolution computed tomography scans were performed during singing at the fundamental mean speaking frequency and the first and second octaves above it. Digital Imaging and Communications in Medicine scan data were rendered and visualized 3-dimensionally using MIMICS software. By superimposition of the different 3-dimensional images, different positions of the thyroid were visualized. The distance from the posterior border of the thyroid was measured in all the examinations.ResultsAll laryngeal cartilages could be three-dimensionally visualized. The magnitude of the thyroidal deformation significantly depends on pitch and significantly correlates with age (r² = 0.7, P < 0.001).ConclusionsThe thyroid cartilage is flexible and its formability is especially important during singing. At higher pitches, the cartilage was more deformed. The larynx in older singers showed less thyroid cartilage deformation.



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Aerodynamic Characteristics of Syllable and Sentence Productions in Normal Speakers

Publication date: Available online 8 January 2018
Source:Journal of Voice
Author(s): Cedric Thiel, Jin Yang, Brianna Crawley, Priya Krishna, Thomas Murry
BackgroundAerodynamic measures of subglottic air pressure (Ps) and airflow rate (AFR) are used to select behavioral voice therapy versus surgical treatment for voice disorders. However, these measures are usually taken during a series of syllables, which differs from conversational speech. Repeated syllables do not share the variation found in even simple sentences, and patients may use their best rather than typical voice unless specifically instructed otherwise. This study examined the potential differences in estimated Ps and AFR in syllable and sentence production and their effects on a measure of vocal efficiency in normal speakers.MethodsProspective study. Measures of estimated Ps, AFR, and aerodynamic vocal efficiency (AVE) were obtained from 19 female and four male speakers ages 22–44 years with no history of voice disorders. Subjects repeated a series of /pa/ syllables and a sentence at comfortable effort level into a face mask with a pressure-sensing tube between the lips.ResultsAVE varies as a function of the speech material in normal subjects. Ps measures were significantly higher for the sentence-production samples than for the syllable-production samples. AFR was higher during sentence production than syllable production, but the difference was not statistically significant. AVE values were significantly higher for syllable versus sentence productions.ConclusionsThe results suggest that subjects increase Ps and AFR in sentence compared with syllable production. Speaking task is a critical factor when considering measures of AVE, and this preliminary study provides a basis for further aerodynamic studies of patient populations.



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Incidence, outcomes, and resource use in children with Stevens-Johnson syndrome and toxic epidermal necrolysis

Abstract

Background/Objectives

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions, typically to drugs or infection. The incidence and outcomes of these conditions in children are unknown. The objective of this study was to report the overall burden of Stevens-Johnson syndrome and toxic epidermal necrolysis in children in the United States.

Methods

We performed a retrospective cohort analysis of children and adolescents younger than 18 years of age using the 2009 and 2012 Kids' Inpatient Database.

Results

We identified 1486 children and adolescents hospitalized with a diagnosis of Stevens-Johnson syndrome or toxic epidermal necrolysis. The national incidence per 100 000 was 6.3 for Stevens-Johnson syndrome, 0.7 for Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome, and 0.5 for toxic epidermal necrolysis. The highest incidence in children was in those aged 11-15 years (38.4 per 100 000). Toxic epidermal necrolysis and Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome were associated with longer stay, greater mortality, and higher hospital charges than those with Stevens-Johnson syndrome. Hospital mortality was highest in children with toxic epidermal necrolysis and in children aged 0-5 years.

Conclusions

The incidence of Stevens-Johnson syndrome and toxic epidermal necrolysis in children is higher than reported in adults, and there are significant age-based variations in incidence and outcomes across the pediatric population. Further study is needed to determine the most effective treatment strategies to reduce costs and improve outcomes in children hospitalized with severe cutaneous reactions.

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Towards an international language for Incontinence-Associated Dermatitis (IAD): design and evaluation of psychometric properties of the Ghent Global IAD Categorisation Tool (GLOBIAD) in 30 countries

Summary

Background

Incontinence-associated dermatitis (IAD) is a specific type of irritant contact dermatitis with different levels of severity. An internationally accepted instrument to assess the severity of IAD in adults with established diagnostic accuracy, agreement, and reliability is needed to support clinical practice and research.

Objectives

To design and psychometrically evaluate the Ghent Global IAD Categorisation Tool (GLOBIAD).

Methods

The design was based on expert consultation using a three-round Delphi procedure with 34 experts from 13 countries. The instrument was tested using IAD photographs reflecting different severity levels in a sample of 823 health professionals in 30 countries. Measures for diagnostic accuracy (sensitivity and specificity), agreement, inter-rater reliability (multi-rater Fleiss kappa), and intra-rater reliability (Cohen's Kappa) were assessed.

Results

The GLOBIAD consists of two categories according to the presence of persistent redness (Cat.1) and skin loss (Cat.2), both subdivided based on the presence of clinical signs of infection. The agreement for differentiating between Cat.1 and Cat.2 was 0.86 [95% confidence interval (CI) 0.86-0.87], with a sensitivity of 90% and a specificity of 84%. The overall agreement was 0.55 (95%CI 0.55-0.56). The Fleiss Kappa for differentiating between Cat.1 and Cat.2 was 0.65 (95%CI 0.65-0.65). The overall Fleiss Kappa was 0.41 (95%CI 0.41-0.41). The Cohen's Kappa for differentiating between Cat.1 and Cat.2 was 0.76 (95%CI 0.75-0.77). The overall Cohen's Kappa was 0.61 (95%CI 0.59-0.62).

Conclusions

The development of the GLOBIAD is a major step forward towards a better systematic assessment of IAD in clinical practice and research worldwide. Further validation is however needed.

This article is protected by copyright. All rights reserved.

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Issue Information–ISSN page

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Instructions for authors

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Epilepsia—January 2018—Announcements

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Thank you to our reviewers

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The effect of single and repeated prefrontal intermittent theta burst stimulation on cortical reactivity and working memory

Publication date: Available online 8 January 2018
Source:Brain Stimulation
Author(s): Sung Wook Chung, Nigel C. Rogasch, Kate E. Hoy, Paul B. Fitzgerald
BackgroundWith an increasing interest in the use of theta burst stimulation (TBS) as a cognitive enhancer and a potential therapeutic tool for psychiatric disorders, there is a need to identify optimal parameters of TBS in the prefrontal cortex.Objective/HypothesisThis study examined the effect of two blocks of prefrontal intermittent TBS (iTBS) on cortical reactivity and working memory performance, compared to one block of iTBS and sham stimulation. We hypothesized that greater cortical effects would be obtained with two blocks of iTBS.MethodsEighteen healthy participants attended three experimental sessions and received either sham, one block or two blocks of iTBS with a 15-min interval. Concurrent transcranial magnetic stimulation with electroencephalography (TMS-EEG) was used to assess the change in cortical reactivity via TMS-evoked potentials. Working memory performance was assessed using the N-back task. Cluster-based permutation statistics and two-way ANOVAs were used for neurophysiological and behavioural data, respectively.ResultsBoth single and two blocks of iTBS resulted in a significant increase in the amplitude of TMS-evoked N100 and P200. No significant differences were observed between active conditions in either neurophysiological changes or working memory performance, and both failed to improve working memory performance relative to sham.ConclusionsTwo blocks of iTBS did not result in stronger measured effects as compared to one block of iTBS. Future studies are needed to identify the optimal stimulation pattern in order to achieve a desired effect. It is also important to establish the best approach in quantifying neuromodulatory effects targeting the prefrontal cortex.



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Effects of TDCS dosage on working memory in healthy participants

Publication date: Available online 8 January 2018
Source:Brain Stimulation
Author(s): Stevan Nikolin, Donel Martin, Colleen K. Loo, Tjeerd W. Boonstra
BackgroundTranscranial direct current stimulation (tDCS) has been found to improve working memory (WM) performance in healthy participants following a single session. However, results are mixed and the overall effect size is small. Interpretation of these results is confounded by heterogeneous study designs, including differences in tDCS dose (current intensity) and sham conditions used.AimsWe systematically investigated the effect of tDCS dose on working memory using behavioural and neurophysiological outcomes.MethodsIn a single-blind parallel group design, 100 participants were randomised across five groups to receive 15 min of bifrontal tDCS at different current intensities (2 mA, 1 mA, and three sham tDCS conditions at 0.034 mA, 0.016 mA, or 0 mA). EEG activity was acquired while participants performed a WM task prior to, during, and following tDCS. Response time, accuracy and an event-related EEG component (P3) were evaluated.ResultsWe found no significant differences in response time or performance accuracy between current intensities. The P3 amplitude was significantly lower in the 0 mA condition compared to the 0.034 mA, 1 mA and 2 mA tDCS conditions. Changes in WM accuracy were moderately correlated with changes in frontal P3 amplitude (channel Fz) following tDCS compared to baseline levels (r = 0.34).ConclusionsWorking memory was not significantly altered by tDCS, regardless of dose. The P3 amplitude showed that stimulation at 1 mA, 2 mA and a sham condition (0.034 mA) had biological effects, with the largest effect size for 1 mA stimulation. These findings indicate higher sensitivity of neurophysiological outcomes to tDCS and suggests that sham stimulation previously considered inactive may alter neuronal function.



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Reviewer thank you list

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Editorial Board

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Training Groups

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Expanded genomic profiling of circulating tumor cells in metastatic breast cancer patients to assess biomarker status and biology over time

Purpose: We profiled circulating tumor cells (CTCs) patients to study the biology of blood-borne metastasis and to monitor biomarker status in metastatic breast cancer (MBC).

Methods: CTCs were isolated from 105 MBC patients using EPCAM-based immunomagnetic enrichment and fluorescence-activated cells sorting (IE/FACs), 28 of whom had serial CTC analysis (74 samples, 2-5 time points). CTCs were subjected to microfluidic-based multiplex QPCR array of 64 cancer-related genes (n=151) and genome-wide copy number analysis by array comparative genomic hybridization (n=49).

Results: Combined transcriptional and genomic profiling showed that CTCs were 26% ESR1-ERBB2-, 48% ESR1+ERBB2-, and 27% ERBB2+. Serial testing showed that ERBB2 status were more stable over time compared to ESR1 and proliferation (MKI67) status. While cell-to-cell heterogeneity was observed at the single cell level, with increasingly stable expression in larger pools, patient-specific CTC expression 'fingerprints' were also observed. CTC copy number profiles clustered into three groups based on the extent of genomic aberrations and the presence of large chromosomal imbalances. Comparative analysis showed discordance in ESR1/ER (27%) and ERBB2/HER2 (23%) status between CTCs and matched primary tumors. CTCs in 65% of the patients were considered to have low proliferation potential. Patients who harbored CTCs with high proliferation (MKI67) status had significantly reduced progression-free survival (p=0.0011) and overall survival (p=0.0095) compared to patients with low proliferative CTCs.

Conclusions: We demonstrate an approach for complete isolation of EPCAM-positive CTCs and downstream comprehensive transcriptional/genomic characterization to examine the biology and assess breast cancer biomarkers in these cells over time.

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Movement-related neural processing in people with congenital mirror movements beyond the (cortical) surface

Publication date: Available online 8 January 2018
Source:Clinical Neurophysiology
Author(s): Renzo Manara, Alessandro Salvalaggio, Angela Favaro, Fabrizio Esposito




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The cortical focus in childhood absence epilepsy; evidence from nonlinear analysis of scalp EEG recordings

Publication date: Available online 8 January 2018
Source:Clinical Neurophysiology
Author(s): Ptolemaios G Sarrigiannis, Yifan Zhao, Fei He, Stephen A Billings, Kathleen Baster, Chris Rittey, John Yianni, Panagiotis Zis, Hualiang Wei, Marios Hadjivassiliou, Richard Grünewald
ObjectiveTo determine the origin and dynamic characteristics of the generalised hyper-synchronous spike and wave (SW) discharges in childhood absence epilepsy (CAE).MethodsWe applied nonlinear methods, the error reduction ratio (ERR) causality test and cross-frequency analysis, with a nonlinear autoregressive exogenous (NARX) model, to electroencephalograms (EEGs) from CAE, selected with stringent electro-clinical criteria (17 cases, 42 absences). We analysed the pre-ictal and ictal strength of association between homologous and heterologous EEG derivations and estimated the direction of synchronisation and corresponding time lags.ResultsA frontal/fronto-central onset of the absences is detected in 13 of the 17 cases with the highest ictal strength of association between homologous frontal followed by centro-temporal and fronto-central areas. Delays consistently in excess of 4 ms occur at the very onset between these regions, swiftly followed by the emergence of "isochronous" (0-2ms) synchronisation but dynamic time lag changes occur during SW discharges.ConclusionsIn absences an initial cortico-cortical spread leads to dynamic lag changes to include periods of isochronous interhemispheric synchronisation, which we hypothesize is mediated by the thalamus.SignificanceAbsences from CAE show ictal epileptic network dynamics remarkably similar to those observed in WAG/Rij rats which guided the formulation of the cortical focus theory.



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A Case of Everolimus-Induced Eyelid Edema

Everolimus is a newer generation mammalian target of rapamycin inhibitor approved for immunosuppressive use in a number of advanced medical conditions. The authors report a unique case of persistent eyelid edema believed to be related to the immunosuppressive therapy. The therapy was being well tolerated despite the persistent eyelid edema, so the patient underwent a bilateral upper eyelid blepharoplasty. The patient responded well with resolution of her eyelid dermatochalasis and markedly decreased edema. Everolimus-induced eyelid edema should be recognized by clinicians as a potential side effect of the medication. Surgical excision of excess eyelid tissue by blepharoplasty can be a successful way to manage this side effect. Everolimus (zortress) was initially approved as an immunosuppressive agent for renal transplantation patients.1 Approval for the treatment of subependymal giant cell astrocytomas associated with tuberous sclerosis, progressive metastatic pancreatic neuroendocrine tumors, human epidermal growth factor receptor 2 negative breast cancer in postmenopausal woman, liver transplantation patients, and well-differentiated neuroendocrine tumors of gastrointestinal or pulmonary origin has followed.2,3 Everolimus is a derivative of sirolimus (rapamune), and similar to sirolimus acts as an inhibitor of mammalian target of rapamycin.1 Few prior studies have reported eyelid edema from sirolomus.4–6 Many prior medications have been implicated in eyelid edema formation.4–11 To date, periocular edema has not been reported as a side effect of everolimus. We report a patient with bilateral upper eyelid edema associated with everolimus therapy requiring surgical intervention to ameliorate the significant skin redundancy and the visual field defect. This report complies with the Declaration of Helsinki and Health Insurance Portability and Accountability Act regulations.

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The Brow Fat Pad Suspension Suture: Safety Profile and Clinical Observations

Purpose: To evaluate the safety, subjectively assess outcome, and emphasize surgical pearls and critical clinical observations of upper blepharoplasty performed in conjunction with the brow fat pad suspension suture procedure, previously referred to as a "browpexy variant" or "brassiere suture procedure." Methods: A retrospective 4-year analysis of patients who underwent the brow fat pad suspension suture with upper blepharoplasty was performed. Adjunctive procedures (brow lift and ptosis repair) were categorized. The surgical technique is detailed with emphasis placed on nuances to aid in optimal outcome. Results: Two hundred and sixteen patients (149 women and 47 men) underwent upper blepharoplasty with the brow fat pad suspension suture. The average patient age is 54 years and follow up is 11 months. One hundred patients had adjudicative brow lift or ptosis repair, and in 20 patients the blepharoplasty was a revision procedure. Subjective assessment of outcome showed excellent aesthetic results with improved brow projection, and enhanced lateral tarsal platform show and eyebrow/eyelid contour. Surgical complications were infrequent and patient satisfaction was high. Conclusions: This initial large series description of the brow fat pad suspension suture demonstrates that it is a safe adjunct to upper blepharoplasty, which the authors believe subjectively improves overall outcome. Evidence-based quantitative assessments of objective measures of surgical results are currently underway.

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Wiesner Nevus of the Eyelid

A healthy 31-year-old female presented with an elevated vascular lesion on the right lower eyelid margin. Histology results from excisional biopsy demonstrated a range of intradermally nested atypical melanocytes with negative staining for BRCA1-associated protein 1, confirming the diagnosis of Wiesner nevus. Wiesner nevi may be a cutaneous hallmark of the BRCA1-associated protein 1–associated cancer susceptibility syndrome, and to our knowledge, this is the first report of such a lesion presenting anywhere on the ocular adnexa.

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Limbal Cysts: A Subset Exhibiting Cornea-Specific Cytokeratins

Two cases of limbal cysts lined by nonkeratinizing epithelium were studied with a panel of cytokeratins. One was a long-standing lesion in a 30-year-old man, whereas the other was excised from a 40-year-old man following pterygium surgery. Each cyst was immunostained with a panel of cytokeratins that were specific exclusively and separately for corneal and conjunctival epithelia. The epithelial lining of each cyst was CK12 positive for corneal epithelium and CK13 negative for conjunctival epithelium. It is hypothesized that a subset of corneoscleral cysts contain corneal epithelium, probably derived from a type of limbal stem cell differentiation.

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Characterizing the Occluded Lacrimal Punctum Using Anterior Segment Optical Coherence Tomography

Purpose: Epiphora is sometimes associated with an absent or occluded lacrimal drainage punctum (or puncta). This study uses noninvasive "enhanced depth" anterior segment optical coherence tomography (OCT) to give improved characterization and understanding of absent or fully occluded puncta and the underlying canaliculus. Methods: Anterior segment spectral domain OCT images were collected prospectively from 9 lower puncta of 6 patients with epiphora and absent or fully occluded puncta, not amenable to dilation in clinic, to see if a canaliculus was visible on OCT imaging below the occluded punctum. Results: An epithelial lined canalicular lumen was visible on OCT in 4 lower eyelid puncta from 2 patients and OCT identified 80% (4/5) of the canaliculi that were located on microscope-assisted punctal exploration. These lumens were seen within 580 μm depth from the eyelid margin surface. A half of the eyes in which a canaliculus was identified on OCT (the 2 eyes in a single patient) had resolution of epiphora following punctoplasty, and the other patient was found to have coexisting nasolacrimal duct stenosis and required later dacryocystorhinostomy. The positive predictive value for identifying a canaliculus on lower eyelid punctal exploration in acquired complete punctal occlusion (excluding the congenital case) was 1, with a negative predictive value of 1. Conclusions: This study demonstrates that canaliculi can be imaged with OCT where formal access is precluded by an occluded punctum. This noninvasive investigation might help predict the likelihood of successful retrieval of a canaliculus at surgical exploration.

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Aesthetic Abstracts and Citations

No abstract available

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Treatment of Pediatric IgG4-Related Orbital Disease With TNF-α Inhibitor

The authors describe a 9-year-old female who presented with swelling, proptosis, and tenderness of the right upper eyelid and MRI imaging demonstrating right lacrimal gland enlargement. After failing treatment with corticosteroids, the patient underwent a biopsy that was consistent with IgG4-related orbital disease. She was subsequently successfully treated with adalimumab (TNF-α inhibitor). This is the first case report of the successful use of a TNF-α inhibitor for the treatment of IgG4-related orbital disease in a child.

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Current Trends in Upper and Lower Eyelid Blepharoplasty Among American Society of Ophthalmic Plastic and Reconstructive Surgery Members

Purpose: To assess current practice patterns for management of upper and lower eyelid blepharoplasty by active American Society of Ophthalmic Plastic and Reconstructive Surgery members. Methods: An invitation to participate in a web-based anonymous survey was sent to the active American Society of Ophthalmic Plastic and Reconstructive Surgery membership via email. The survey consists of 34 questions, both multiple choice and free response, regarding upper and lower eyelid blepharoplasty surgery. Practice patterns for both aesthetic and functional blepharoplasty are assessed. Results: Thirty-four percent (161/472) of American Society of Ophthalmic Plastic and Reconstructive Surgery members polled responded to the survey. Members perform an average of 196 upper eyelid, 46 lower eyelid, and 53 four-eyelid blepharoplasty procedures per year, with 70% of cases being functional and 30% purely aesthetic. Most members prefer monitored care (71%) to local (21%) or general (8%) anesthesia. Eighty-nine percent of surgeons use topical antibiotics after surgery, erythromycin being the most common (51%). Fourteen percent of members use postoperative oral antibiotics, with cephalexin (81%) being most common. In upper eyelid blepharoplasty, orbicularis muscle is excised by 86% of respondents. Orbital fat is excised, when deemed appropriate, in 97% of cases, with nasal fat excised most commonly (88%). Less commonly, fat repositioning (36%) and adjunctive fat grafting (33%) are performed. In lower eyelid blepharoplasty, surgeons report using one or more of the following approaches: transconjunctival (96%), transcutaneous (82%), and both transconjunctival and transcutaneous (51%). Common adjunctive procedures include orbital fat excision (99%), fat repositioning (80%), and lateral canthal suspension (96%). Less common adjunctive procedures include laser skin resurfacing (36%) and chemical peels (29%). Conclusions: This report outlines contemporary practice patterns among active American Society of Ophthalmic Plastic and Reconstructive Surgery members in the management of upper and lower eyelid blepharoplasty. It is important to quantify such data periodically to update the membership as to how this common surgical procedure is approached. This also allows eyelid surgeons to compare their practice patterns with a national group specializing in such surgery.

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Primary Neuroendocrine Tumor of the Orbit Presenting With Acute Proptosis

Primary neuroendocrine tumors of the orbit are exceedingly rare and typically present with gradual, progressive exophthalmos. In this report, an otherwise healthy 64-year-old woman undergoes resection of a well-differentiated neuroendocrine tumor after presenting with acute proptosis. An extensive clinical and radiographic evaluation reveals no other evidence of disease, establishing the diagnosis of a primary neuroendocrine tumor. The case presentation is followed by a brief review of the classification, presentation, and evaluation of orbital neuroendocrine tumors.

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Baby Shampoo Versus Povidone-Iodine or Isopropyl Alcohol in Reducing Eyelid Skin Bacterial Load

Purpose: Baby shampoo is used as an alternative surgical skin preparation, but the evidence supporting its use is scarce with no descriptions of efficacy in the periocular region. The authors compare the efficacy of baby shampoo, povidone-iodine (PI, Betadine) and isopropyl alcohol (IA) in reducing eyelid skin bacterial load. Methods: Prospective, randomized, comparative, and interventional trial. Bacterial load on adult, human eyelid skin was quantitated before and after cleansing with 1) dilute baby shampoo, 2) 10% PI, or 3) 70% IA. Paired skin swabs were collected from a 1 cm2 area of the upper eyelid of subjects before and after a standardized surgical scrub technique. Samples were cultured on 5% sheep blood agar for 24 hours. The number of colony forming units (CFU) was assessed and bacterial load per square centimeter of eyelid skin was quantified. Results: Baseline and postcleansing samples were assessed from 42 eyelids of 42 subjects (n = 14 for each of baby shampoo, PI, and IA). Before cleansing, similar amounts of bacterial flora were grown from all specimens (median log CFU/cm2 = 2.04 before baby shampoo, 2.01 before PI, 2.11 before IA; p > 0.05). All 3 cleansing agents significantly reduced the bacterial load (p 0.05). Change from baseline in bacterial load was statistically similar for all 3 agents (median reduction in log CFU/cm2 = 1.28 with baby shampoo, 1.57 with PI, 1.40 with IA; p > 0.05). These corresponded to bacterial load reductions of 96.3%, 96.6%, and 98.4% for baby shampoo, PI, and IA, respectively. Conclusions: Baby shampoo achieved comparable diminution in eyelid skin bacterial load to PI or IA. These data suggest baby shampoo may be an effective preoperative cleansing agent.

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Rituximab Monotherapy Is Effective in Treating Orbital Necrobiotic Xanthogranuloma

The authors report a case of a patient with bilateral orbital necrobiotic xanthogranuloma and no associated systemic paraproteinemia. Orbital biopsy showed strong expression of CD20-positive cells. The patient was treated with systemic rituximab monotherapy, with excellent clinical response and marked regression of the orbital lesions on imaging. At the time of writing, the patient has been treated with bimonthly rituximab maintenance therapy for 22 months and has stable clinical and imaging findings with sustained response to treatment and no reported side effects. To the authors' knowledge, this is the first reported case of orbital necrobiotic xanthogranuloma successfully treated with rituximab monotherapy. They hope that this well-documented case will encourage clinicians to consider rituximab monotherapy as a possible treatment option, albeit one entailing an off-label use of this drug, for patients with necrobiotic xanthogranuloma of the orbit.

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Prophylactic Antibiotics for Enucleation and Evisceration: A Retrospective Study and Systematic Literature Review

Purpose: To report surgical site infection (SSI) rates of eviscerations and enucleations with implants performed without perioperative intravenous (IV) antibiotics or postoperative oral antibiotics, and to give SSI prevention recommendations. Methods: A single-center retrospective chart review was performed after obtaining institutional review board approval. Charts were found by Current Procedural Terminology codes. Demographics, surgical indication, procedure, implant, antibiotic use, and postoperative course were recorded. SSIs occurring within 30 days after surgery were reviewed and postoperative infection rates were determined. Results: Four hundred eighty-one cases from January 1999 to December 2015 were analyzed. There were 102 eviscerations with implants, 314 enucleations with implants, 23 enucleations without implants, 23 implant exchanges, 15 implants placed secondarily after enucleation, and 4 implant removals. Seventy cases (14.6%) were given perioperative IV antibiotics, and in this group one periorbital infection occurred unrelated to orbital surgery (1.4%). Of the 411 cases (85.4%) not given perioperative IV antibiotics, 1 of 87 eviscerations with implants developed an SSI (1.1%), 2 of 273 enucleations with implants developed SSIs (0.7%), and none of the 13 enucleations without implants developed SSIs. Conclusions: To our knowledge, this is the first published case series reporting SSI rates of enucleations and eviscerations with implants performed without perioperative IV antibiotics or postoperative oral antibiotics. With infection rates comparing favorably to other case series where antibiotics were given, the routine use of perioperative IV antibiotics and postoperative oral antibiotics for enucleations and eviscerations may not be indicated.

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Keratocystic Odontogenic Tumor Involving the Orbital Apex

No abstract available

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Rethinking Our Definition of Postoperative Success: A Comparative Analysis of Three Upper Eyelid Retraction Repair Techniques Using Novel Metrics to Capture Functional and Aesthetic Outcomes

Purpose: To compare 3 upper eyelid retraction repair techniques and introduce novel metrics, which enhance the analysis of postoperative aesthetic outcomes. Methods: Retrospective review with Image J 1.48 digital analysis of patients who underwent repair of thyroid-related upper eyelid retraction at the University of Iowa from 1996 to 2014 via 1 of 3 surgical techniques, septum-opening levator recession with Muellerectomy, modified septum-preserving levator recession with Muellerectomy, and modified septum-preserving full-thickness blepharotomy, was conducted. Photographs were obtained preoperatively, 3 to 6 months postoperatively, and at last follow up (>6 months) and evaluated by digital image analysis (denoted by "i"). Outcome measures assessed were marginal reflex distance (iMRD1), temporal-to-nasal ratio, tarsal platform show (iTPS), pupil to visible eyelid crease, brow fat span (iBFS), tarsal platform show to brow fat span ratio (iTPS:iBFS), and tarsal platform show minimizing power (iTPS-minimizing power). Results: A total of 121 eyelids (28 septum-opening levator recession with Muellerectomy, 66 septum-preserving levator recession with Muellerectomy, and 27 septum-preserving full-thickness blepharotomy) from 74 patients were evaluated with a mean follow up of 24.2 months. There were no statistically significant differences between techniques in terms of iMRD1 or temporal-to-nasal ratio reduction at either time point (intertechnique p values of 0.17 to >0.99). The percentage of eyelids from subjects undergoing bilateral intervention that achieved a final iMRD1 between 2.50 mm and 4.50 mm was similar (intertechnique p value of 0.23), with no difference regarding the number of subjects demonstrating iMRD1 symmetry within 1 mm (intertechnique p value of 0.15). Though iTPS elongation was greater at 3 to 6 months with septum-opening compared with the combined septum-preserving techniques (p value of 0.04), this difference was not maintained at final follow up (p value of >0.99). There was no difference in terms of iTPS symmetry at time of final follow up (intertechnique p value of 0.69). The pupil to visible eyelid crease was unchanged in all techniques (p values >0.99). Mean changes in iBFS at final follow up were −1.27 mm, −0.44 mm, and +0.55 mm for septum-opening levator recession with Muellerectomy, septum-preserving levator recession with Muellerectomy, and septum-preserving full-thickness blepharotomy (p values of 0.01, 0.49, and >0.99, respectively). Mean iTPS:iBFS ratios at final follow up were not statistically different between techniques (intertechnique p value of 0.10) and no difference in symmetry was demonstrated (intertechnique p value of 0.47). Median values for iTPS-minimizing power were: −0.83, −0.93, and −1.01 for septum-opening levator recession with Muellerectomy, septum-preserving levator recession with Muellerectomy, and septum-preserving full-thickness blepharotomy, respectively (intertechnique p value of 0.54). Conclusions: Each technique appropriately lowered the eyelid and improved contour without intertechnique variability. Septum-preserving techniques demonstrated less iTPS elongation initially, but this difference was not maintained. The visible eyelid crease height (pupil to visible eyelid crease) remained stable in all techniques, indicating that the iTPS elongation seen with each technique was secondary to reduction in iMRD1 and the iBFS reduction seen with septum-opening levator recession with Muellerectomy was due to brow descent. No intertechnique differences in the amount of iTPS elongation relative to iMRD1 reduction (i.e., the novel iTPS-minimizing power) were seen. Given that each procedure evaluated yielded similar results, technique selection may be guided by surgeon experience and preference.

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Re: Commentary on “Localizing the Lost Rectus Muscle Using the Connective Tissue Framework Revisiting the Tunnel Technique”

No abstract available

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Risk Factors Affecting the Prognosis of Descending Necrotizing Mediastinitis From Odontogenic Infection.

Related Articles

Risk Factors Affecting the Prognosis of Descending Necrotizing Mediastinitis From Odontogenic Infection.

J Oral Maxillofac Surg. 2017 Dec 13;:

Authors: Qu L, Liang X, Jiang B, Qian W, Zhang W, Cai X

Abstract
PURPOSE: Descending necrotizing mediastinitis (DNM) is a serious complication of head and neck infections and has an excessively high mortality rate owing to the lack of understanding of DNM. We assessed the clinical characteristics, diagnosis, treatment, and outcomes of odontogenic DNM and evaluated the risk factors affecting the prognosis of DNM to provide an up-to-date overview for clinical practice.
MATERIALS AND METHODS: We performed a retrospective cohort study, enrolling a sample of patients with DNM due to odontogenic infection who had been referred from January 2013 to December 2016. The patients were classified into the surviving and deceased groups. The primary predictors in the present study were the presence of multiple comorbidities, complications, demographic data (age, gender), laboratory tests (white blood cell count, percentage of neutrophils), and time (duration before diagnosis, length of hospital stay). The primary outcome variable was the patient outcome (dead or alive). The continuous variables were evaluated using Student's t test or the t test, and the categorical and binary variables were compared using the χ2 test or Fisher exact test.
RESULTS: A total of 81 patients (68 men, 13 women; median age of 57.2 ± 12.2 years) were included. The mortality was 4.9%. The most frequent cause of DNM was periapical periodontitis (66.7%). The lower posterior molars were involved in 39.5% of the cases. Treatment consisted of antibiotic therapy, aggressive transcervical mediastinal drainage (n = 74), and thoracotomy (n = 7). The associated risk factors for mortality were complications (P < .005) and severe sepsis or septic shock (P < .001) on bivariate analysis.
CONCLUSIONS: Septic shock and complications were the risk factors that correlated with a poor prognosis. A timely diagnosis and use of aggressive mediastinal drainage are fundamental to reducing the incidence of complications and the development of septic shock in odontogenic DNM patients.

PMID: 29306716 [PubMed - as supplied by publisher]

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Viable tumor in salvage neck dissections in head and neck cancer: Relation with initial treatment, change of lymph node size and human papillomavirus

Publication date: February 2018
Source:Oral Oncology, Volume 77
Author(s): Karlijn van den Bovenkamp, Bart Dorgelo, Maartje G. Noordhuis, Bernard F.A.M. van der Laan, Bert van der Vegt, Hendrik P. Bijl, Jan L. Roodenburg, Boukje A.C. van Dijk, Sjoukje F. Oosting, Ed M.D. Schuuring, Johannes A. Langendijk, Gyorgy B. Halmos, Boudewijn E.C. Plaat
ObjectivesTo identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections.Materials and MethodsRetrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in combination with carboplatin/5-fluorouracil (n = 42) or with cetuximab (n = 12).ResultsViable tumor was detected in 41% of all neck dissections. Univariate analysis revealed initial treatment with radiotherapy without systemic therapy (OR 6.93, 95%CI: 2.28–21.07, p < .001), increased lymph node size after initial treatment compared to pretreatment CT scan (OR 20.48, 95%CI: 2.46–170.73, p = .005), more extensive neck dissections (OR 8.40, 95%CI: 2.94–23.98, p < .001), and human papillomavirus negative cancer (OR 4.22, 95%CI: 1.10–16.22, p = .036) as predictors of viable tumor. Patients with decreased or stable, but persistently enlarged lymph node size after chemoradiation had a significantly lower chance of viable tumor (OR 0.15, 95%CI: 0.05–0.41, p < .001). Disease-specific 5-year survival was 34% in case of viable tumor, and 78% when no viable tumor was found (p < .001).ConclusionsViable tumor in salvage neck dissections is associated with reduced survival. Radiotherapy alone, human papillomavirus negative cancer and increase in lymph node size, are associated with viable tumor in salvage neck dissections. In case of decreased or stable lymph node size after chemoradiation, watchful waiting could be considered.



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Synaptic markers of cognitive decline in neurodegenerative diseases: a proteomic approach

Abstract

Cognitive changes occurring throughout the pathogenesis of neurodegenerative diseases are directly linked to synaptic loss. We used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospectively followed patients with Alzheimer's disease, Parkinson's disease with dementia, dementia with Lewy bodies and older adults without dementia. In total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels of 25 synaptic proteins were significantly altered in the various dementia groups. Significant loss of SNAP47, GAP43, SYBU (syntabulin), LRFN2, SV2C, SYT2 (synaptotagmin 2), GRIA3 and GRIA4 were further validated on a larger cohort comprised of 92 brain samples using ELISA or western blot. Cognitive impairment before death and rate of cognitive decline significantly correlated with loss of SNAP47, SYBU, LRFN2, SV2C and GRIA3 proteins. Besides differentiating Parkinson's disease dementia, dementia with Lewy bodies, and Alzheimer's disease from controls with high sensitivity and specificity, synaptic proteins also reliably discriminated Parkinson's disease dementia from Alzheimer's disease patients. Our results suggest that these particular synaptic proteins have an important predictive and discriminative molecular fingerprint in neurodegenerative diseases and could be a potential target for early disease intervention.

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Current principles of surgery for retroperitoneal sarcomas

Surgery for primary retroperitoneal sarcomas (RPS) often requires a technically challenging, en bloc multivisceral resection to optimize outcomes. Surgery may also be appropriate for patients with localized recurrent RPS. Anatomic considerations and tumor biology driven by histologic subtype may guide the extent of resection in patients with RPS. This review provides an overview of the current surgical principles for primary and recurrent RPS.

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Validation of clinical prognostic scores for patients treated with curative-intent for recurrent colorectal liver metastases

Background

Scoring systems were developed to stratify patients with colorectal liver metastases considered for liver resection into different risk groups. Such scores have never been evaluated in recurrent liver metastases. The aim of this study was to evaluate whether these scores are applicable to patients with recurrent colorectal liver metastases and treated with curative intent.

Methods

We retrospectively analyzed data from 375 consecutive patients who underwent liver surgery for colorectal liver metastases between June 2010 and August 2015. Seventy-three patients developed liver-limited recurrence treated with curative intent. The predictive value of 6 scores (Fong, Sofocleous, Nagashima, Nordlinger, Konopke, and the Basingstoke index) was assessed in this set of patients.

Results

Median follow-up was 36.2 months. Overall survival and progression-free survival were 33.6 and 5.6 months, respectively. When scores were applied for OS, none showed a significant stratification between patients, although Nagashima's score showed a significant difference in overall survival between patients from the low-risk group and those from the intermediate- and high-risk groups (40.8 vs 30.5 months, P = 0.039). For PFS, only Fong's score showed a statistically significant stratification (6.6 vs 4.7 months, P = 0.027).

Conclusion

Scoring systems are of limited-value in stratifying patients operated on for recurrent colorectal liver metastases.

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Mid- to long-term clinical outcome of giant cell tumor of bone treated with calcium phosphate cement following thorough curettage and phenolization

Background and Objectives

Giant cell tumors of bone (GCTB) are intermediate and locally aggressive bone tumor. Calcium phosphate cement (CPC) is a bone void filler used in orthopaedic surgery. This study investigated the clinical outcome of GCTB treated with thorough curettage, phenolization, and CPC.

Methods

We investigated 26 patients with at least 36 months of follow-up. The mean age and follow-up were 37 years (range: 19-63) and 87 months (range: 38-169), respectively. Radiological outcomes including consolidation of CPC to the surrounding bone, cortical bone defect remodeling, and clinical outcomes were investigated.

Results

The consolidation of CPC to the surrounding bone was excellent in 22 cases (84.6%), good in three (11.5%), and acceptable in one (3.8%). Local recurrence occurred in three cases (11.5%). Pulmonary metastasis occurred in one case (3.8%). Cortical bone defect remodeling appeared in 22 cases (84.6%). The mean Musculoskeletal Tumour Society score was 28.7 (95.7%). Osteoarthritis, chronic synovitis, and fracture were observed in one case each (3.8%), which were managed conservatively.

Conclusions

Phenolization did not prevent the consolidation of CPC to the bone. CPC provided biological interface and long lasting stability without internal fixation, with comparable complication rates to other published series.

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Trends of genetic screening in patients with pheochromocytoma and paraganglioma: 15-year experience in a high-volume tertiary referral center

Background and Objectives

Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.

Methods

We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50).

Results

Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P < 0.001). A total of 67% followed up on the referral. The prevalence of genetic mutation was 50% (21/42 tested). The percentage with a genetic syndrome was 23%, 28%, and 22% respectively for groups 1, 2, and 3.

Conclusions

Referral for genetic counseling significantly increased in the past 15 years. However, only two-thirds of patients followed up with genetic counselors and, therefore, clinicians can do more to improve the adherence rate for genetic counseling.

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Evaluation of extended antibiotic prophylaxis in patients undergoing indicated non-cosmetic panniculectomy at the time of gynecologic surgery

Background

Panniculectomy at time of gynecologic surgery is used to improve visualization and prevent major complications in morbidly obese patients. We examine the role of extended antibiotic prophylaxis in prevention of surgical site infections (SSI), specifically based on patient risk factors (hypertension, diabetes, smoking).

Methods

A prospective cohort study of all women who underwent panniculectomy at the time of gynecologic surgery from September 2014 to March 2016 at a university-affiliated hospital. The EAP cohort received standard antibiotics (cefazolin, 2 g) and continued oral antibiotic (doxycycline) for 10 days afterwards. Patients in this cohort were compared to historical controls from the same institution from 1990 to 2014. Specific attention was paid to the reduction of SSIs in patients with hypertension, diabetes, and a history of smoking.

Results

The mean age was 56.0 ± 12.6 years, and mean body mass index 44.5 ± 9.3 kg/m² (range 31-63.4 kg/m²). The EAP cohort experienced fewer surgical-site infections overall, however these results were not significantly decreased from the historical controls, (13/56 [23.2%] vs 94/300 [31.3%]; P = 0.469).

Conclusion

Though initially promising, extended antibiotic prophylaxis did not reduce surgical site infections in the obese women after indicated non-cosmetic panniculectomy at the time of gynecologic surgery.

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Stridor combined with other sleep breathing disorders in multiple system atrophy: A tailored treatment?

To determine the frequency of sleep breathing disorders in multiple systemic atrophy (MSA, combining Parkinsonism, cerebellar syndrome and dysautonomia) and evaluate the benefit/tolerance of various modes of ventilation.

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Sleep-disordered breathing is associated with disturbed cardiac repolarization in patients with a coronary artery bypass graft surgery

The development of malignant ventricular arrhythmias due to abnormal cardiac repolarization is a major complication after coronary artery bypass graft surgery (CABG). Sleep-disordered breathing (SDB) is linked to prolonged cardiac repolarization in non-surgical patients. This study evaluates cardiac repolarization in patients with and without SDB who underwent CABG.

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Sex-specific associations between extreme sleep duration and prevalence of cardio-cerebral vascular disease: a community-based cross-sectional study

Most previous studies on sleep duration and cardio-cerebral vascular disease (CCVD) association have not adequately controlled for many confounders. The current study prospectively examined the association of sleep duration with CCVD prevalence in a Chinese community population; cardiovascular risk factors, chronic diseases, and sleep quality were taken into consideration.

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Nasopharyngeal changes during healthy children of 8–13 years old in China: a longitudinal study

Introduction: Nasopharynx is an important compartment of the upper airway and respiratory system. It is closely associated with the characteristic craniofacial skeletal pattern related to sleep breathing and has gradual changes as age grows. The present study aimed to investigate the development pattern of the nasopharynx during rapid puberty growth period.

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Aerodynamic Characteristics of Syllable and Sentence Productions in Normal Speakers

Aerodynamic measures of subglottic air pressure (Ps) and airflow rate (AFR) are used to select behavioral voice therapy versus surgical treatment for voice disorders. However, these measures are usually taken during a series of syllables, which differs from conversational speech. Repeated syllables do not share the variation found in even simple sentences, and patients may use their best rather than typical voice unless specifically instructed otherwise. This study examined the potential differences in estimated Ps and AFR in syllable and sentence production and their effects on a measure of vocal efficiency in normal speakers.

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How Age and Frequency Impact the Thyroid Cartilages of Professional Singers

Young professional singers can easily reach very high pitches. In contrast, older singers often complain that they have to exert substantially more laryngopharyngeal force to reach the same high pitch compared with their earlier years. Various factors such as the property changes of the mucosa and ossification that impact the singing apparatus were suggested as explanations in the literature. The aim of this study was to analyze thyroid deformation—and thereby stiffness indirectly—during singing as a potential reason for this phenomenon.

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How do oral and maxillofacial surgeons manage concussion?

Craniofacial trauma results in distracting injuries that are easy to see, and as oral and maxillofacial surgeons (OMFS) we gravitate towards injuries that can be seen and are treatable surgically. However, we do tend not to involve ourselves (and may potentially overlook) injuries that are not obvious either visually or radiographically, and concussion is one such. We reviewed the records of 500 consecutive patients who presented with facial fractures at the Queen Elizabeth Hospital, Birmingham, to identify whether patients had been screened for concussion, and how they had been managed.

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Ultrastructural damage in Streptococcus mutans incubated with saliva and histatin 5.

Publication date: Available online 8 January 2018
Source:Archives of Oral Biology
Author(s): A.M. Fernández-Presas, Y. Márquez Torres, R. García González, A. Reyes Torres, I. Becker Fauser, H. Rodríguez Barrera, B. Ruíz García, R. Toloza Medina, J. Delgado Domínguez, J.L. Molinarí Soriano
ObjectiveTo study the ultrastructural alterations induced in Streptococcus mutans (ATCC 25175) incubated with saliva, saliva plus histatin 5 and histatin 5.MethodsS. mutans incubated with saliva histatin 5 or a combination of both were morphologically analyzed and counted. The results were expressed as (CFU)ml⁻¹. Ultrastructural damage was evaluated by transmission electron microscopy. Ultrastructural localization of histatin 5 was examined using immunogold labeling. Apoptotic cell death was determined by flow cytometry (TUNEL).ResultsA decrease in the bacteria numbers was observed after incubation with saliva, saliva with histatin 5 or histatin 5 compared to the control group (p<0.0001). Ultrastructural damage in S. mutans incubated with saliva was found in the cell wall. Saliva plus histatin 5 induced a cytoplasmic granular pattern and decreased the distance between the plasma membrane bilayers, also found after incubation with histatin 5, together with pyknotic nucleoids. Histatin 5 was localized on the bacterial cell walls, plasma membranes, cytoplasm and nucleoids. Apoptosis was found in the bacteria incubated with saliva (63.9%), saliva plus histatin 5 (71.4%) and histatin 5 (29.3%). Apoptosis in the control bacteria was 0.2%.ConclusionsAntibacterial activity against S. mutans and the morphological description of damage induced by saliva and histatin 5 was demonstrated. Pyknotic nucleoids observed in S. mutans exposed to saliva, saliva plus histatin 5 and histatin 5 could be an apoptosis-like death mechanism. The knowledge of the damage generated by histatin 5 and its intracellular localization could favor the design of an ideal peptide as a therapeutic agent.



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SUPRAGINGIVAL AND SUBGINGIVAL MICROBIOTA FROM PATIENTS WITH POOR ORAL HYGIENE SUBMITTED TO RADIOTHERAPY FOR HEAD AND NECK CANCER TREATMENT

Publication date: Available online 8 January 2018
Source:Archives of Oral Biology
Author(s): Elerson Gaetti-Jardim, Ellen Cristina Gaetti Jardim, Christiane Marie Schweitzer, Júlio Cesar Leite da Silva, Murilo Moura Oliveira, Danilo Chizzolini Masocatto, Cauê Monteiro dos Santos
ObjectiveThis case-control study aimed to evaluate the effects of conventional radiotherapy (RT) on the prevalence and populations of oral microorganisms in head and neck cancer patients who did not receive adequate preventive dental care. It was hypothesized that side effects of radiotherapy could be associated with radiation dose, microbiological aspects, and socioeconomic conditions of the patients.DesignTwenty-eight dentate patients with head and neck cancer submitted to RT were included in the study. Radiation dose received varied from 4320 to 7020 cGy. Patients with the same demographic and health conditions, but no history of cancer or antineoplastic treatment were used as controls. Clinical examinations were carried out before RT, 15–22 days after starting RT, immediately after and 6 months after RT. Supra and subgingival biofilms were collected and cultivated onto selective and non-selective media. Isolates were identified by biochemical and physiological characteristics. Stimulated and unstimulated salivary flow rate and saliva buffer capacity were also determined.ResultsMucositis, dermatitis, xerostomia, dysgeusia, dysphagia and candidiasis were common after starting RT and during the treatment period. Xerostomia was followed by a decrease in salivary pH and buffer capacity, which showed association with the increase of cariogenic cocci and yeast populations, which were also associated with deterioration of hygiene. Candida and family Enterobacteriaceae showed increased prevalence with RT, and were associated with the occurrence of mucositis and xerostomia.ConclusionsModifications in oral biofilms of irradiated patients showed association with xerostomia and hygiene conditions, which reinforces the necessity of improving patient compliance to oral health care programs.



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A worldwide comparison of the management of surgical treatment of advanced oral cancer

Microvascular surgery following tumor resection has become an important field of oral and maxillofacial surgery (OMFS). Following the results from management of T1/T2 floor-of-mouth and tongue squamous cell carcinoma (SCC) in German-speaking countries, Europe, and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T3/T4 SCC of the maxillary and mandibular alveolar process and tongue.

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Movement-related neural processing in people with congenital mirror movements beyond the (cortical) surface

We read with interest the article of Franz and Fu, highlighting the existence of abnormal pre-movement planning processes in subjects with congenital mirror movements (CMM) (Franz and Fu, 2017). By means of an accurate EEG study paradigm, the authors suggested a failure of inhibitory mechanisms at the level of the supplementary and primary motor cortices as a phenomenon associated to CMM in non-syndromic patients. According to the authors, besides a supposed abnormal decussation of the pyramidal cortico-spinal tract, the abnormal control of the pre-movement cortical activity is the key factor in the pathogenesis of CMM.

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The cortical focus in childhood absence epilepsy; evidence from nonlinear analysis of scalp EEG recordings

Gibbs, in his pioneering work on the newly developed electroencephalogram, described in 1935 the characteristic 3Hz spike and wave (SW) discharge of "petit mal" (Gibbs FA, 1935). In 1941 Jasper and Kershman on EEGs of patients with "petit mal" seizures reported the abrupt onset and offset of bilateral highly synchronous SW discharges, and postulated a subcortical origin as the generator of the attacks (Jasper et al., 1941). A midline placed pacemaker projecting to both hemispheres could explain both the bilateral synchrony and the generalised onset and termination of the absences.

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Alveolar corticotomies for accelerated orthodontics: A systematic review

It has been suggested that alveolar corticotomies may accelerate tooth movement, broaden the scope of malocclusion types that can be treated orthodontically, decrease the need for extractions, and support long-term stability. Several techniques have been proposed, although the indications, ideal design and technical characteristics, potential complications, and objective clinician and patient satisfaction remain unclear. This systematic review aimed to provide scientific support to validate alveolar corticotomies as a reliable approach to accelerated orthodontics.

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What’s in a Name? Cell Fate Reprogramming in Sarcomagenesis

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Kevin B. Jones
Differentiation features in cancer cells are typically attributed to the cell of origin. In this issue of Cancer Cell, Drummond et al. demonstrate a transdifferentiation program apparent in rhabdomyosarcomas (cancers with skeletal muscle differentiation features) arising through cell fate reprogramming from a single oncogene activation in endothelial cell precursors.

Teaser

Differentiation features in cancer cells are typically attributed to the cell of origin. In this issue of Cancer Cell, Drummond et al. demonstrate a transdifferentiation program apparent in rhabdomyosarcomas (cancers with skeletal muscle differentiation features) arising through cell fate reprogramming from a single oncogene activation in endothelial cell precursors.


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Characterizing the Killer Colorectal Carcinomas

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Stanley R. Hamilton
In this issue of Cancer Cell, Yaeger et al. report mutations, copy number variations, and selected rearrangements from a large series of metastatic colorectal carcinomas and primaries that produced metastases. The results provide important insights into differences in anatomical site of origin, age at onset, etiologic factors, and therapeutic responses.

Teaser

In this issue of Cancer Cell, Yaeger et al. report mutations, copy number variations, and selected rearrangements from a large series of metastatic colorectal carcinomas and primaries that produced metastases. The results provide important insights into differences in anatomical site of origin, age at onset, etiologic factors, and therapeutic responses.


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Molecular Predictors of Gastric Neoplastic Progression

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Paul Lochhead, Emad M. El-Omar
In this issue of Cancer Cell, Huang et al. describe comprehensive genetic and epigenetic profiling of gastric intestinal metaplasia lesions from a longitudinal cohort in which outcome data allowed for identification of potential markers of gastric neoplastic progression.

Teaser

In this issue of Cancer Cell, Huang et al. describe comprehensive genetic and epigenetic profiling of gastric intestinal metaplasia lesions from a longitudinal cohort in which outcome data allowed for identification of potential markers of gastric neoplastic progression.


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A TFIID-SAGA Perturbation that Targets MYB and Suppresses Acute Myeloid Leukemia

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Yali Xu, Joseph P. Milazzo, Tim D.D. Somerville, Yusuke Tarumoto, Yu-Han Huang, Elizabeth L. Ostrander, John E. Wilkinson, Grant A. Challen, Christopher R. Vakoc
Targeting of general coactivators is an emerging strategy to interfere with oncogenic transcription factors (TFs). However, coactivator perturbations often lead to pleiotropic effects by influencing numerous TFs. Here we identify TAF12, a subunit of TFIID and SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia (AML) progression. We trace this dependency to a direct interaction between the TAF12/TAF4 histone-fold heterodimer and the transactivation domain of MYB, a TF with established roles in leukemogenesis. Ectopic expression of the TAF4 histone-fold fragment can efficiently squelch TAF12 in cells, suppress MYB, and regress AML in mice. Our study reveals a strategy for potent MYB inhibition in AML and highlights how an oncogenic TF can be selectively neutralized by targeting a general coactivator complex.

Graphical abstract

Teaser

Xu et al. show that TAF12 is a coactivator of MYB and protects MYB from degradation. TAF12, in a heterodimer with TAF4, interacts with the transactivation domain of MYB. Perturbation of this interaction by squelching TAF12 impairs MYB activity and leads to regression of acute myeloid leukemia in mouse models.


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TFIID and MYB Share a Therapeutic Handshake in AML

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Charles C. Bell, Mark A. Dawson
Selectively disrupting oncogenic transcription factors in cancer remains an elusive ambition of targeted therapeutics. In this issue of Cancer Cell, Xu et al. provide an elegant proof-of-concept study demonstrating that interaction between MYB and the general transcriptional coactivator TFIID can be specifically disrupted to mediate a therapeutic effect in AML.

Teaser

Selectively disrupting oncogenic transcription factors in cancer remains an elusive ambition of targeted therapeutics. In this issue of Cancer Cell, Xu et al. provide an elegant proof-of-concept study demonstrating that interaction between MYB and the general transcriptional coactivator TFIID can be specifically disrupted to mediate a therapeutic effect in AML.


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TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S. Rugo, Matthew F. Krummel, Lisa M. Coussens, Brian Ruffell
Intratumoral CD103⁺ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103⁺ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8⁺ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors. Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.

Graphical abstract

Teaser

de Mingo Pulido et al. show that intratumoral CD103⁺ dendritic cells (DCs) highly express TIM-3. Anti-TIM-3 antibody promotes CXCL9 expression by these DCs, which enhances the function of CD8⁺ T cells, thereby improving paclitaxel's therapeutic activity in breast cancer models.


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Hedgehog Pathway Drives Fusion-Negative Rhabdomyosarcoma Initiated From Non-myogenic Endothelial Progenitors

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Catherine J. Drummond, Jason A. Hanna, Matthew R. Garcia, Daniel J. Devine, Alana J. Heyrana, David Finkelstein, Jerold E. Rehg, Mark E. Hatley
Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that histologically resembles embryonic skeletal muscle. RMS occurs throughout the body and an exclusively myogenic origin does not account for RMS occurring in sites devoid of skeletal muscle. We previously described an RMS model activating a conditional constitutively active Smoothened mutant (SmoM2) with aP2-Cre. Using genetic fate mapping, we show SmoM2 expression in Cre-expressing endothelial progenitors results in myogenic transdifferentiation and RMS. We show that endothelium and skeletal muscle within the head and neck arise from Kdr-expressing progenitors, and that hedgehog pathway activation results in aberrant expression of myogenic specification factors as a potential mechanism driving RMS genesis. These findings suggest that RMS can originate from aberrant development of non-myogenic cells.

Graphical abstract

Teaser

Using genetic fate mapping, Drummond et al. show that hedgehog pathway activation in endothelial progenitors results in aberrant expression of myogenic specification factors, myogenic transdifferentiation, and rhabdomyosarcoma (RMS). The finding may explain how RMS develops in sites devoid of skeletal muscle.


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Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): A. Gordon Robertson, Juliann Shih, Christina Yau, Ewan A. Gibb, Junna Oba, Karen L. Mungall, Julian M. Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M. Lichtenberg, Melanie Kucherlapati, Patrick K. Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A. Bristow, Katherine A. Hoadley, Lisa Iype, Matthew T. Chang, Andrew D. Cherniack, Christopher Benz, Gordon B. Mills, Roel G.W. Verhaak, Klaus G. Griewank, Ina Felau, Jean C. Zenklusen, Jeffrey E. Gershenwald, Lynn Schoenfield, Alexander J. Lazar, Mohamed H. Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M. Cebulla, Michelle D. Williams, Martine J. Jager, Sarah E. Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E. Woodman




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Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Xuxu Sun, Sam C. Wang, Yonglong Wei, Xin Luo, Yuemeng Jia, Lin Li, Purva Gopal, Min Zhu, Ibrahim Nassour, Jen-Chieh Chuang, Thomas Maples, Cemre Celen, Liem H. Nguyen, Linwei Wu, Shunjun Fu, Weiping Li, Lijian Hui, Feng Tian, Yuan Ji, Shuyuan Zhang, Mahsa Sorouri, Tae Hyun Hwang, Lynda Letzig, Laura James, Zixi Wang, Adam C. Yopp, Amit G. Singal, Hao Zhu




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Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Qianghu Wang, Baoli Hu, Xin Hu, Hoon Kim, Massimo Squatrito, Lisa Scarpace, Ana C. deCarvalho, Sali Lyu, Pengping Li, Yan Li, Floris Barthel, Hee Jin Cho, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Siyuan Zheng, Edward Chang, Charles-Etienne Gabriel Sauvé, Adriana Olar, Zheng D. Lan, Gaetano Finocchiaro, Joanna J. Phillips, Mitchel S. Berger, Konrad R. Gabrusiewicz, Guocan Wang, Eskil Eskilsson, Jian Hu, Tom Mikkelsen, Ronald A. DePinho, Florian Muller, Amy B. Heimberger, Erik P. Sulman, Do-Hyun Nam, Roel G.W. Verhaak




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Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy for personalized cancer treatment

Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately the vast majority of patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) in patients with PDA.

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Contrast harmonic EUS for the prediction of pancreatic neuroendocrine tumor aggressiveness (with videos)

Contrast-harmonic EUS (CH-EUS) has the ability to depict a tumor microvasculature. Decreased microvascular density has been identified as a factor associated with tumor aggressiveness. We aimed to study the accuracy of CH-EUS for the prediction of pancreatic neuroendocrine tumor (PNET) aggressiveness.

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Anesthesia for Same Day Discharge After Craniotomy: Review of a Single Center Experience

Same day discharge or outpatient surgery for intracranial procedures has become possible with the advent of image-guided minimally invasive approaches to surgery and availability of short-acting anesthetic agents. In addition, patient satisfaction and the benefits of avoiding hospital stay have resulted in the evolution of neurosurgical day surgery. We reviewed our experience and the available literature to determine the perioperative factors involved which have promoted and will improve this concept in the future. Craniotomy and biopsy for supratentorial brain tumors and surgical clipping of intact cerebral aneurysms have been successfully performed as day surgeries. Patient perceptions and satisfaction surveys have helped in better understanding and delivery of care and successful outcomes. There are major differences in health care across the globe along with socioeconomic, medicolegal, and ethical disparities, which must be considered before widespread application of this approach. Nevertheless, collaborative effort by surgeons, anesthesiologists, and nurses can help in same day discharge of patients after cranial neurosurgery. Veena Sheshadri, MD, Department of Neuroanesthesia and Neurocritical Care, Gleneagles Global Hospitals, Bengaluru, Karnataka, India. All the authors contributed substantially to the conception and design of the manuscript and to the interpretation of data. S.V., V.L., and M.P.: contributed to the literature search, acquisition, and analysis of data. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Lashmi Venkatraghavan, MD, FRCA, FRCPC, Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada (e-mail: lashmi.venkatraghavan@uhn.on.ca). Received May 29, 2017 Accepted November 28, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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