Electroconvulsive seizures influence dendritic spine morphology and BDNF expression in a neuroendocrine model of depression

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Kristen. R. Maynard, John W. Hobbs, Sumita Rajpurohit, Keri Martinowich
BackgroundElectroconvulsive therapy (ECT) is a rapid and effective treatment for major depressive disorder. Chronic stress-induced depression causes dendrite atrophy and deficiencies in brain-derived neurotrophic factor (BDNF), which are reversed by anti-depressant drugs. Electroconvulsive seizures (ECS), an animal model of ECT, robustly increase BDNF expression and stimulate dendritic outgrowth.ObjectiveThe present study aims to understand cellular and molecular plasticity mechanisms contributing to the efficacy of ECS following chronic stress-induced depression.MethodsWe quantify Bdnf transcript levels and dendritic spine density and morphology on cortical pyramidal neurons in mice exposed to vehicle or corticosterone and receiving either Sham or ECS treatment.ResultsECS rescues corticosterone-induced defects in spine morphology and elevates Bdnf exon 1 and exon 4-containing transcripts in cortex.ConclusionsDendritic spine remodeling and induction of activity-induced BDNF in the cortex represent important cellular and molecular plasticity mechanisms underlying the efficacy of ECS for treatment of chronic stress-induced depression.



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Overlap of large-scale brain networks may explain the similar cognitive improvement of single-site vs multi-site rTMS in Alzheimer's disease

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Ruth Alcalá-Lozano, Eduardo A. Garza-Villarreal




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Opposite effects of lateralised transcranial alpha versus gamma stimulation on auditory spatial attention

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Malte Wöstmann, Johannes Vosskuhl, Jonas Obleser, Christoph S. Herrmann
BackgroundSpatial attention relatively increases the power of neural 10-Hz alpha oscillations in the hemisphere ipsilateral to attention, and decreases alpha power in the contralateral hemisphere. For gamma oscillations (>40 Hz), the opposite effect has been observed. The functional roles of lateralised oscillations for attention are currently unclear.HypothesisIf lateralised oscillations are functionally relevant for attention, transcranial stimulation of alpha versus gamma oscillations in one hemisphere should differentially modulate the accuracy of spatial attention to the ipsi-versus contralateral side.Methods20 human participants performed a dichotic listening task under continuous transcranial alternating current stimulation (tACS, vs sham) at alpha (10 Hz) or gamma (47 Hz) frequency. On each trial, participants attended to four spoken numbers on the left or right ear, while ignoring numbers on the other ear. In order to stimulate a left temporo-parietal cortex region, which is known to show marked modulations of alpha power during auditory spatial attention, tACS (1 mA peak-to-peak amplitude) was applied at electrode positions TP7 and FC5 over the left hemisphere.ResultsAs predicted, unihemispheric alpha-tACS relatively decreased the recall of targets contralateral to stimulation, but increased recall of ipsilateral targets. Importantly, this spatial pattern of results was reversed for gamma-tACS.ConclusionsResults provide a proof of concept that transcranially stimulated oscillations can enhance spatial attention and facilitate attentional selection of speech. Furthermore, opposite effects of alpha versus gamma stimulation support the view that states of high alpha are incommensurate with active neural processing as reflected by states of high gamma.



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Transcutaneous nerve stimulation via the tragus: are we stimulating the vagus nerve?

Publication date: Available online 5 April 2018
Source:Brain Stimulation
Author(s): Andreas M. Burger, Bart Verkuil




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Involuntary and voluntary electroconvulsive therapy: A case-control study

Publication date: Available online 5 April 2018
Source:Brain Stimulation
Author(s): Martha Finnegan, Stephanie O'Connor, Declan M. McLoughlin
BackgroundIt is not known whether results of clinical research in ECT can be used to guide treatment decisions for those having involuntary ECT, who are not represented in trial populations.ObjectiveWe aimed to compare courses of involuntary ECT with matched voluntary ECT courses in terms of clinical and demographic factors, treatment requirements, and outcomes.MethodWe performed a retrospective case-control study examining a five-year sample of involuntary ECT courses and an age-, gender- and time-matched voluntary ECT control sample.ResultsWe examined 48 involuntary and 96 control voluntary ECT courses. While groups differed at baseline in terms of diagnosis, illness severity and illness characteristics, there were no differences in treatment outcomes after ECT or six-month readmission rates.ConclusionOur findings suggest that research on capacitous ECT patients is applicable to those having involuntary ECT.



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Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Bashar W. Badran, Oliver J. Mithoefer, Caroline E. Summer, Nicholas T. LaBate, Chloe E. Glusman, Alan W. Badran, William H. DeVries, Philipp M. Summers, Christopher W. Austelle, Lisa M. McTeague, Jeffrey J. Borckardt, Mark S. George
BackgroundOptimal parameters of transcutaneous auricular vagus nerve stimulation (taVNS) are still undetermined. Given the vagus nerve's role in regulating heart rate (HR), it is important to determine safety and HR effects of various taVNS parameters.ObjectiveWe conducted two sequential trials to systematically test the effects of various taVNS parameters on HR.Methods15 healthy individuals participated in the initial two-visit, crossover exploratory trial, receiving either tragus (active) or earlobe (control) stimulation each visit. Nine stimulation blocks of varying parameters (pulse width: 100 μs, 200 μs, 500 μs; frequency: 1 Hz, 10 Hz, 25 Hz) were administered each visit. HR was recorded and analyzed for stimulation-induced changes. Using similar methods and the two best parameters from trial 1 (500μs 10 Hz and 500μs 25 Hz), 20 healthy individuals then participated in a follow-up confirmatory study.ResultsTrial 1- There was no overall effect of the nine conditions on HR during stimulation. However multivariate analysis revealed two parameters that significantly decreased HR during active stimulation compared to control (500μs 10 Hz and 500μs 25 Hz; p < 0.01). Additionally, active taVNS significantly attenuated overall sympathetic HR rebound (post-stimulation) compared to control (p < 0.001). Trial 2-For these two conditions, active taVNS significantly decreased HR compared to control (p = 0.02), with the strongest effects at 500μs 10 Hz (p = 0.032).ConclusionThese studies suggest that 60s blocks of tragus stimulation are safe, and some specific parameters modulate HR. Of the nine parameters studied, 500μs 10 Hz induced the greatest HR effects.



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Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters

Publication date: Available online 5 April 2018
Source:Brain Stimulation
Author(s): Douglas Teixeira Leffa, Bruna Bellaver, Artur Alban Salvi, Carla de Oliveira, Wolnei Caumo, Eugenio Horacio Grevet, Felipe Fregni, André Quincozes-Santos, Luis Augusto Rohde, Iraci L.S. Torres
BackgroundTranscranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear.Objective/HypothesisWe evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS.MethodsAdult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated.ResultsTDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines.ConclusionTDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored.



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Apocrine hidrocystoma on the genitalia of a 9‐year‐old girl

Pediatric Dermatology, EarlyView.


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Idiopathic facial aseptic granuloma—A diagnostic challenge in pediatric dermatology

Pediatric Dermatology, EarlyView.


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A case of extensive acquired progressive lymphangioma

Pediatric Dermatology, EarlyView.


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Occult dysraphism presenting with acro‐osteolysis

Pediatric Dermatology, EarlyView.


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Compound heterozygous mutations in desmoplakin associated with skin fragility, follicular hyperkeratosis, alopecia, and nail dystrophy

Pediatric Dermatology, EarlyView.


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Evidence‐based dosing of maintenance subcutaneous immunotherapy: a contemporary review of state‐of‐the‐art practice

International Forum of Allergy &Rhinology, EarlyView.


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Chernobyl-related thyroid cancer

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A prognostic role for Low tri-iodothyronine syndrome in acute stroke patients: A systematic review and meta-analysis

Publication date: June 2018
Source:Clinical Neurology and Neurosurgery, Volume 169
Author(s): Nayan Lamba, Chunming Liu, Hasan Zaidi, M.L.D. Broekman, Thomas Simjian, Chen Shi, Joanne Doucette, Steven Ren, Timothy R. Smith, Rania A. Mekary, Adomas Bunevicius
BackgroundLow triiodothyronine (T3) syndrome could be a powerful prognostic factor for acute stroke; yet, a prognostic role for low T3 has not been given enough importance in stroke management. This meta-analysis aimed to evaluate whether low T3 among acute stroke patients could be used as a prognostic biomarker for stroke severity, functional outcome, and mortality.MethodsStudies that investigated low T3 prognostic roles in acute stroke patients were sought from PubMed/Medline, Embase, and Cochrane databases through 11/23/2016. Pooled estimates of baseline stroke severity, mortality, and functional outcomes were assessed from fixed-effect (FE) and random-effects (RE) models.ResultsEighteen studies met the inclusion criteria. Six studies (1,203 patients) provided data for low-T3 and normal-T3 patients and were meta-analyzed. Using the FE model, pooled results revealed low-T3 patients exhibited a significantly higher stroke severity, as assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission (mean difference = 3.18; 95%CI = 2.74, 3.63; I² = 61.9%), had 57% higher risk of developing poor functional outcome (RR = 1.57; 95%CI = 1.33,1.8), and had 83% higher odds of mortality (Peto-OR = 1.83; 95%CI = 1.21, 1.99) compared to normal-T3 patients. In a univariate meta-regression analysis, the low-T3 and stroke severity association was reduced in studies with higher smokers% (slope = −0.11; P = 0.02), higher hypertension% (slope = −0.11; P = 0.047), older age (slope = −0.54; P = 0.02), or longer follow-up (slope = −0/17, P < 0.01). RE models yielded similar results. No significant publication bias was observed for either outcome using Begg's and Egger's tests.ConclusionsLow-T3 syndrome in acute stroke patients is an effective prognostic factor for predicting greater baseline stroke severity, poorer functional outcome, and higher overall mortality risk.



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Improvement of health related quality of life in patients with recurrent glioma treated with bevacizumab plus daily temozolomide as the salvage therapy

Publication date: June 2018
Source:Clinical Neurology and Neurosurgery, Volume 169
Author(s): Yong Liu, Fuqiang Feng, Peigang Ji, Bolin Liu, Shunnan Ge, Chen Yang, Miao Lou, Jinghui Liu, Baofu Li, Guodong Gao, Yan Qu, Liang Wang
ObjectivesBevacizumab (BEV) plus daily temozolomide (TMZ) as a salvage therapy have been recommended to recurrent glioma. The objective of this retrospective study was to evaluate the effect of the combined regimen on health related quality of life (HRQL) and treatment response in patients with recurrent glioma.Patients and MethodsTwenty patients with recurrent glioma were treated with BEV (5–10 mg/kg, i.v. every 2 weeks) plus daily TMZ (daily, 50 mg/m²). The treatment response was evaluated via the RANO criteria. HRQL were measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (QLQ-C30) and Brain Module (QLQ-BN20).ResultsTwenty patients received a total of 85 cycles of BEV with a median number of 4 cycles (range: 2–10). No patients showed complete response (CR) to treatment. Twelve patients had partial response (PR), stable disease (SD) in 5 patients with, and 3 patients showed progressive disease (PD). In the functioning domains of QLQ-C30, physical functioning, cognitive functioning and emotional functioning significantly improved after the second cycle of BEV compared to baseline, with the mean score of 45.0 vs. 64.0 (p = 0.020), 55.8 vs. 71.7 (p = 0.020) and 48.3 vs. 67.5 (p = 0.015), respectively. In the symptom scales, the scores of pain and nausea/vomiting significantly decreased compared to baseline from the mean score of 39.1 to 20.0 (p = 0.020) and 29.2 to 16.7 (p = 0.049), respectively. Score of global health status also increased from 47.5 to 63.3 (p = 0.001). As determined with the QLQ-BN20, motor dysfunction (43.3 vs. 25.0, p = 0.021), weakness of legs (36.7 vs. 18.3, p = 0.049), headache (38.3 vs. 20.0, p = 0.040), and drowsiness (50.0 vs. 30.0, p = 0.026) after the second cycle of BEV also significantly improved compared to baseline.ConclusionBEV plus daily TMZ as a salvage therapy improved HRQL in patients with recurrent glioma.



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The Bursts and Lulls of Multimodal Interaction: Temporal Distributions of Behavior Reveal Differences Between Verbal and Non‐Verbal Communication

Cognitive Science, EarlyView.


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Proton therapy for central nervous system tumors in children

Pediatric Blood &Cancer, EarlyView.


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Malignant tumors misdiagnosed as benign vascular anomalies

Pediatric Blood &Cancer, EarlyView.


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Diminished Dentate Gyrus Filtering of Cortical Input Leads to Enhanced Area Ca3 Excitability after Mild Traumatic Brain Injury

Journal of Neurotrauma, Ahead of Print.


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Chloroquine Promotes the Recovery of Acute Spinal Cord Injury by Inhibiting Autophagy-Associated Inflammation and Endoplasmic Reticulum Stress

Journal of Neurotrauma, Ahead of Print.


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Cognition, Health-Related Quality of Life, and Depression Ten Years after Moderate to Severe Traumatic Brain Injury: A Prospective Cohort Study

Journal of Neurotrauma, Ahead of Print.


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Reducing the risk of post-surgical cancer recurrence: a perioperative anti-inflammatory anti-stress approach

Future Oncology, Ahead of Print.


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Management of oncological patients in the digital era: anatomic pathology and nuclear medicine teamwork

Future Oncology, Ahead of Print.


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Treatment of venous stenosis in oncologic patients

Future Oncology, Ahead of Print.


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Indoor/outdoor relationships, sources and cancer risk assessment of NPAHs and OPAHs in PM2.5 at urban and suburban hotels in Jinan, China

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Yanyan Li, Lingxiao Yang, Xiangfeng Chen, Pan Jiang, Ying Gao, Junmei Zhang, Hao Yu, Wenxing Wang
Paired indoor and outdoor measurements of 16 NPAHs and 5 OPAHs in PM2.5 were conducted at urban and suburban sites during January 2016 in Jinan, China. The concentrations of both indoor and outdoor NPAHs and OPAHs were higher at the urban site compared with the suburban site. 9N-ANT (16–42%), 2+3N-FLA (15–51%), 2N-PYR (6–20%), and 1N-PYR (4–6%) were the dominant NPAHs at all sites, and 9-FO (61–81%) was the most abundant OPAHs. Solid fuel combustion, motor vehicle exhausts, and secondary generation were the main sources of the PAH derivatives in this study area. The I/O ratios of 90% of NPAHs and OPAHs at the first urban indoor site (abbreviated as URI¹, Green Tree Inn) and the suburban indoor site (abbreviated as SUI, the Seven Star Hotel) were <1.00 indicating that many of the compounds measured indoors originated from outdoor sources. At the second urban indoor site (abbreviated as URI², Shandong University Hotel), the I/O ratios of 2- and 3-ring NPAHs and OPAHs were >1.00, which was likely due to cooking activities occurring near the measurement site. Measurements of outdoor 2+3N-FLA/1N-PYR revealed mainly primary emission at the urban site and secondary sources at the suburban site, the average ratios were 3.76 and 12.22, respectively. The average ratio of 2+3N-FLA/2N-PYR at all sites was 3.3, indicating that the OH-initiated reaction was the dominant secondary formation pathway. Nighttime ratios of 2+3N-FLA/1N-PYR were significantly higher than the daytime ratios at all sites. The difference was especially pronounced during heavily polluted conditions at the suburban site, which suggests that heavy pollution and nighttime conditions promote secondary production. Additionally, the cancer risk was highest in urban outdoor (abbreviated as URO) when the population expose to the level as the outdoor air in the urban. The risk suggested that adults may be at a higher cancer risk.



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Analysis of spatial-temporal heterogeneity in remotely sensed aerosol properties observed during 2005–2015 over three countries along the Gulf of Guinea Coast in Southern West Africa

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Mangamana Aklesso, K. Raghavendra Kumar, Lingbing Bu, Richard Boiyo
In the present study, the spatial-temporal distribution and estimation of trends of different aerosol optical properties, and related impact factors were investigated over three countries: Ghana, Togo, and Benin along the Gulf of Guinea Coast in Southern West Africa (SWA). For this purpose, long-term satellite derived aerosol optical properties (aerosol optical depth at 550 nm; AOD550, Ångström exponent at 470–660 nm; AE470-660, and absorption aerosol index; AAI) retrieved from the Moderate-resolution Imaging Spectroradiometer (MODIS) and Ozone Monitoring Instrument (OMI) during January 2005–December 2015 were utilized. The annual mean spatial distribution of AOD550 was found to be high (>0.55) over the southern coastal area, moderate-to-high (0.35–0.55) over the central, and low (<0.35) over northern parts of the study domain. The seasonal mean variations showed high (low) values of AOD550 and AAI during the Harmattan or dry (wet) season. Whereas, low (high) AE470-660 values were characterized during the Harmattan (wet) season. Linear trend analysis revealed a decreasing trend in AOD550 and AAI, and increasing trend in AE470-660. Further, an investigation on the potential drivers to AOD distribution over the SWA revealed that precipitation, NDVI, and terrain were negatively correlated with AOD. Finally, the HYSPLIT derived back trajectory analyses revealed diverse transport pathways originated from the North Atlantic Ocean, Sahara Desert, and Nigeria along with locally generated aerosols.

Graphical abstract

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Hypoxia upregulates the expression of the pluripotency markers in the stem cells from human deciduous teeth

Abstract

Objectives

Cultivation under hypoxia promotes different responses in the mesenchymal stem cells and it has been producing promising results for clinical applications. Pulp tissue from deciduous teeth is a source of stem cells which has a high proliferative potential but this is usually discarded. This study has evaluated the effects of hypoxia on proliferation, apoptosis, and the expression of the pluripotency-related genes of the stem cells from human exfoliated deciduous teeth (SHED).

Materials and methods

The cells were isolated from dental pulp (n = 5) and characterized as mesenchymal stem cells, in accordance with the International Society for Cell Therapy. The cells were cultivated under hypoxia (3% oxygen) and compared to the normoxia cells (21% oxygen). The proliferation rate was evaluated by the Ki67 antibody for up to 7 days, while the metabolic activity was measured by the wst-8 assay for up to 14 days. The apoptotic cells were analyzed by Annexin V and propidium iodide staining at 24 h and 4 and 7 days. The expression of the pluripotent genes (OCT4, SOX2, and NANOG) was quantified by qPCR after 24 h, or 7 days, when cultivated under hypoxia or normoxia.

Results

No differences in the metabolic activity, the proliferation rate, and the apoptosis of SHED when cultivated under hypoxia or normoxia (p > 0.05) were observed. The expression of the pluripotent genes was significantly higher after 24 h and 7 days of the cells that were exposed to hypoxia (p < 0.01).

Conclusion

These findings have indicated an increase of the pluripotency-related genes within 7 days as being the main advantage of SHED culture under hypoxia.

Clinical relevance

Hypoxia culture may help maintain the quiescent state of the SHED, which could be advantageous for their future clinical applications.

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BRAF gene copy number and mutant allele frequency correlate with time to progression in metastatic melanoma patients treated with MAPK inhibitors.

Metastatic melanoma is characterized by complex genomic alterations including a high rate of mutations in driver genes and widespread deletions and amplifications encompassing various chromosome regions. Among them, chromosome 7 is frequently gained in BRAF mutant melanoma, inducing a mutant allele-specific imbalance. Although BRAF amplification is a known mechanism of acquired resistance to therapy with MAPK inhibitors, it is still unclear if BRAF copy number variation and BRAF mutant allele imbalance at baseline can be associated with response to treatment. In this study, we used a multimodal approach to assess BRAF copy number and mutant allele frequency in pre-treatment melanoma samples from 46 patients who received MAPK inhibitor-based therapy and we analyzed the association with progression free survival. We found that 65% patients displayed BRAF gains, often supported by chromosome 7 polysomy. In addition, we observed that 64% patients had a balanced BRAF mutant/wild-type allele ratio, while 14% and 23% patients had low and high BRAF mutant allele frequency, respectively. Notably, a significantly higher risk of progression was observed in patients with a diploid BRAF status vs. those with BRAF gains (HR = 2.86; 95% CI 1.29-6.35; p = 0.01) and in patients with low percentage vs. those with a balanced BRAF mutant allele percentage (HR = 4.54, 95% CI 1.33-15.53; p = 0.016). Our data suggest that quantitative analysis of the BRAF gene could be useful to select the melanoma patients who are most likely to benefit from therapy with MAPK inhibitors.

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APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency

APTO-253 is a small molecule with anti-proliferative activity against cell lines derived from a wide range of human malignancies. We sought to determine the mechanisms of action and basis for resistance to APTO-253 so as to identify synthetic lethal interactions that can guide combination studies. The cellular pharmacology of APTO-253 was analyzed in Raji lymphoma cells and a subline selected for resistance (Raji/253R). Using LC/MS/ESI analysis, APTO-253 was found to convert intracellularly to a complex containing one molecule of iron and three molecules of APTO-253 [Fe(253)3]. The intracellular content of Fe(253)3 exceeded that of the native drug by ~18-fold, and Fe(253)3 appears to be the most active form. Treatment of cells with APTO-253 caused DNA damage, which led us to ask if cells deficient in homologous recombination (i.e., loss of BRCA1/2 function) were hypersensitive to this drug. It was found that loss of either BRCA1 or BRCA2 function in multiple isogenic paired cell lines resulted in hypersensitivity to APTO-253 of a magnitude similar to the effects of PARP inhibitors, olaparib. Raji cells selected for 16-fold acquired resistance had 16-fold reduced accumulation of Fe(253)3. RNA-seq analysis revealed that over-expression of the ABCG2 drug efflux pump is a key mechanism of resistance. ABCG2 overexpressed HEK-293 cells were resistant to APTO-253 and inhibition of ABCG2 reversed resistance to APTO-253 in Raji/253R. APTO-253 joins the limited repertoire of drugs which can exploit defects in homologous recombination and is of particular interest because it does not produce myelosuppression.

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APTO-253 stabilizes G-quadruplex DNA, inhibits MYC expression and induces DNA damage in acute myeloid leukemia cells

APTO-253 is a Phase 1 clinical stage small molecule that selectively induces CDKN1A (p21), promotes G0/G1 cell cycle arrest and triggers apoptosis in acute myeloid leukemia (AML) cells without producing myelosuppression in various animal species and humans. Differential gene expression analysis identified a pharmacodynamic effect on MYC expression, as well as induction of DNA repair and stress response pathways. APTO-253 was found to elicit a concentration-dependent and time-dependent reduction in MYC mRNA expression and protein levels. Gene ontogeny and structural informatic analyses suggested a mechanism involving G-quadruplex (G4) stabilization. Intracellular pharmacokinetic studies in AML cells revealed that APTO-253 is converted intracellularly from a monomer to a ferrous complex [Fe(253)3]. FRET assays demonstrated that both monomeric APTO-253 and Fe(253)3 stabilize G4 structures from telomeres, MYC and KIT promoters but do not bind to non-G4 double stranded DNA. Although APTO-253 exerts a host of mechanistic sequelae, the effect of APTO-253 on MYC expression and its downstream target genes, on cell cycle arrest, DNA damage, and stress responses can be explained by the action of Fe(253)3 and APTO-253 on G-quadruplex DNA motifs.

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New Visions and Current Evidence for Safety in Anesthesia

No abstract available

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American Society for Enhanced Recovery: Advancing Enhanced Recovery and Perioperative Medicine

As the population ages, the increasing surgical volume and complexity of care are expected to place additional care delivery burdens in the perioperative setting. In this age of integrated multidisciplinary care of the surgical patients, there is increasing recognition that an evidence-based perioperative pathway is associated with the optimal outcomes. These pathways, collectively referred to as Enhanced Recovery Pathways, have resulted in shortened length of hospital stay, reduced complications, and variance in outcomes, as well as earlier return to baseline activities. The American Society for Enhanced Recovery (ASER) is a multispecialty, nonprofit international organization, dedicated to the practice of enhanced recovery in perioperative patients through education and research. Perioperative Quality Initiatives were formed whose intent is to organize a series of consensus conferences on topics of interest related to perioperative medicine. The journal affiliation between American Society for Enhanced Recovery and Anesthesia& Analgesia will enable these evidence-based practices to be disseminated widely and swiftly to the practicing perioperative health care professionals so they can be adopted to improve the quality of perioperative surgical care. Accepted for publication March 12, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Tong J. Gan, MD, MBA, MHS, FRCA, Department of Anesthesiology, Stony Brook University, HSC Level 4, Rm 060, Stony Brook, NY 11794. Address e-mail to tong.gan@stonybrookmedicine.edu. © 2018 International Anesthesia Research Society

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Dezocine Alleviates Morphine-Induced Dependence in Rats

BACKGROUND: Opioid dependence is a major public health issue without optimal therapeutics. This study investigates the potential therapeutic effect of dezocine, a nonaddictive opioid, in opioid dependence in rat models. METHODS: Dezocine was administered intraperitoneally to a morphine-dependent rat model to investigate its effect on withdrawal and conditioned place preference (CPP). Effect of dezocine on morphine withdrawal syndrome and CPP was analyzed using 2-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Buprenorphine and vehicle solution containing 20% (v/v) dimethyl sulfoxide were used for positive and negative control, respectively. The astrocytes activation in nucleus accumbens was assessed by immunofluorescence assay of glial fibrillary acidic protein. Effect of dezocine and buprenorphine on the internalization of κ opioid receptor (KOR) was investigated using Neuro2A expressing KOR fused to red fluorescent protein tdTomato (KOR-tdT). Buprenorphine and dezocine were screened against 44 G-protein–coupled receptors, ion channels, and transporter proteins using radioligand-binding assay to compare the molecular targets. RESULTS: The mean withdrawal score was reduced in rats treated with 1.25 mg·kg−1 dezocine compared to vehicle-treated control animals starting from the day 1 (mean difference: 7.8; 95% confidence interval [CI], 6.35–9.25; P

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Case Studies in Adult Intensive Care Medicine

No abstract available

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Lack of Evidence for Ceiling Effect for Buprenorphine Analgesia in Humans

No abstract available

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Potential Benefits of Sodium-Glucose Cotransporter-2 Inhibitors in the Perioperative Period

No abstract available

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Diagnostic Accuracy of Point-of-Care Gastric Ultrasound

BACKGROUND: Pulmonary aspiration of gastric contents is associated with significant perioperative morbidity and mortality. Previous studies have investigated the validity, reliability, and possible clinical impact of gastric ultrasound for the assessment of gastric content at the bedside. In the present study, we examined the accuracy (evaluated as sensitivity, specificity, and likelihood ratios) of point-of-care gastric ultrasound to detect a "full stomach" in a simulated scenario of clinical equipoise. METHODS: After a minimum fasting period of 8 hours, 40 healthy volunteers were randomized in a 1:1 ratio to either remain fasted or ingest a standardized quantity of clear fluid or solid. Each subject was randomized twice on 2 independent study sessions at least 24 hours apart. A gastric ultrasound examination was performed by a blinded sonographer following a standardized scanning protocol. Using a combination of qualitative and quantitative findings, the result was summarized in a dichotomous manner as positive (any solid or >1.5 mL/kg of clear fluid) or negative (no solid and ≤1.5 mL/kg of clear fluid) for full stomach. RESULTS: Data from 80 study sessions were analyzed. In this simulated clinical scenario with a pretest probability of 50%, point-of-care gastric ultrasound had a sensitivity of 1.0 (95% confidence interval [CI], 0.925–1.0), a specificity of 0.975 (95% CI, 0.95–1.0), a positive likelihood ratio of 40.0 (95% CI, 10.33–∞), a negative likelihood ratio of 0 (95% CI, 0–0.072), a positive predictive value of 0.976 (95% CI, 0.878–1.0), and a negative predictive value of 1.0 (95% CI, 0.92–1.0). CONCLUSIONS: Our results suggest that bedside gastric ultrasound is highly sensitive and specific to detect or rule out a full stomach in clinical scenarios in which the presence of gastric content is uncertain. Accepted for publication February 27, 2018. Funding: This study was supported by a peer-reviewed grant from Physician Services Incorporated, Ontario, Canada. Conflicts of Interest: See Disclosures at the end of the article. Trial Registry Number: Registration ID: NCT02588495. Reprints will not be available from the authors. Address correspondence to Anahi Perlas, MD, FRCPC, Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Department of Anesthesia, University of Toronto, 399 Bathurst St, McLaughlin Pavilion 2–405, Toronto, ON M5T 2S8, Canada. Address e-mail to anahi.perlas@uhn.ca. © 2018 International Anesthesia Research Society

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Profound Intraoperative Hypotension Associated With Transfusion via the Belmont Fluid Management System

This retrospective observational case series conducted at 2 large academic centers over a 4-year period consists of 15 cases of profound hypotension in surgical patients immediately after initiation of the Belmont Fluid Management System for rapid transfusion of blood products. Halting the infusion and administering vasoactive agents led to resolution of hypotension. Repeat transfusion with the Belmont system resulted in repeat hypotension unless counteracted with vasopressors. No etiology was elucidated. This represents the largest documented association of acute hypotensive transfusion reaction with any rapid infusion system in surgical patients. Accepted for publication February 1, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Joanna Miller, MD, Mount Sinai Hospital, 1 Gustave Levy Pl, New York, NY 10129. Address e-mail to joanna.miller@mountsinai.org. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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Comparison of Intraoperative Sedation With Dexmedetomidine Versus Propofol on Acute Postoperative Pain in Total Knee Arthroplasty Under Spinal Anesthesia: A Randomized Trial

BACKGROUND: In patients undergoing total knee arthroplasty under spinal anesthesia, we compared the postoperative analgesic effect of intraoperative sedation with dexmedetomidine versus propofol. We hypothesized that sedation with dexmedetomidine would result in lower postoperative opioid analgesic consumption than with propofol. METHODS: Forty-eight patients were enrolled and randomly assigned to either a dexmedetomidine group (n = 24), which received a loading dose of 1 μg/kg dexmedetomidine over 10 minutes, followed by a continuous infusion of 0.1–0.5 μg·kg−1·hour−1, or a propofol group (n = 24), which received a continuous infusion of propofol via a target-controlled infusion to maintain the effect-site concentration within a range of 0.5–2.0 μg/mL. The drug infusion rate was determined according to the sedation level, targeting a modified observer's assessment of alertness/sedation score of 3 or 4. The cumulative amounts of fentanyl administered via intravenous patient-controlled analgesia were recorded at 24 and 48 hours postoperatively (primary outcome). The postoperative numerical rating scale for pain was assessed at 6, 12, 24, and 48 hours (secondary outcome). The postoperative use of additional rescue analgesic (ketoprofen) and antiemetic drugs was also compared between the 2 groups at 24 and 48 hours. RESULTS: Dexmedetomidine significantly reduced postoperative fentanyl consumption (median [interquartile range]) during 0–24 hours (45 [30–71] vs 150 [49–248] μg, P = .004; median difference = −105 μg [99.98% CI, 210–7.5]), 24–48 hours (90 [45–143] vs 188 [75–266] μg, P = .005; median difference = −98 μg [99.98% CI, 195–45]), and 0–48 hours (135 [68–195] vs 360 [146–480] μg, P = .003; median difference = −225 μg [99.98% CI, 405–7.5]). The numerical rating scale (median [interquartile range]) was lower at 6 hours (1 [0–2] vs 2 [1–3], P = .003), 12 hours (1 [1–2] vs 3 [2–3], P

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Gastrointestinal Tract Vasculopathy: Clinicopathology and Description of a Possible “New Entity” With Protean Features

Noninfectious gastrointestinal (GI) vasculopathic disorders are rare and are often overlooked in histopathologic examination or when forming differential diagnoses due to their rarity. However, involvement of the GI tract may lead to serious complications, including ischemia and perforation. Since awareness of the types of vasculopathy that may involve the GI tract is central to arriving at a correct diagnosis, we reviewed our institutional experience with GI tract vasculopathy in order to enhance diagnostic accuracy of these rare lesions. We report the clinical and histologic features of 16 cases (excluding 16 cases of immunoglobulin A vasculitis) diagnosed over a 20-year period. Of the 16 patients, 14 presented with symptoms related to the GI vasculopathy (including 2 presenting with a mass on endoscopic examination). The remaining 2 patients presented with incarcerated hernia and invasive adenocarcinoma. The vasculopathy was not associated with systemic disease and appeared limited to the GI tract in 8 patients. Eight had associated systemic disease, but only 6 had a prior diagnosis. The underlying diagnoses in these 6 patients included systemic lupus erythematosus (1), dermatomyositis (2), rheumatoid arthritis (1), eosinophilic granulomatosis with polyangiitis (1), and Crohn disease (1). One patient with granulomatous polyangiitis and 1 patient with systemic lupus erythematosus initially presented with GI symptoms. The 8 cases of isolated GI tract vasculopathy consisted of enterocolic lymphocytic phlebitis (4), idiopathic myointimal hyperplasia of the sigmoid colon (1), idiopathic myointimal hyperplasia of the ileum (1), granulomatous vasculitis (1), and polyarteritis nodosa-like arteritis (1). Isolated GI tract vasculopathy is rare, but appears to be almost as common as that associated with systemic disease. The chief primary vasculopathies are enterocolic lymphocytic colitis and idiopathic myointimal hyperplasia. Although the latter occurs predominantly in the left colon, rare examples occur in the small bowel and likely represent a complex, more protean disorder. Conflicts of Interest and Funding Statements: The authors have disclosed that they have no significant relationships with or financial interest in any commercial companies pertaining to this study. Correspondence: Teri A. Longacre, MD, Department of Pathology, Stanford Medicine, Stanford, CA 94305 (e-mail: longacre@stanford.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Poorly Differentiated Clusters Predict Colon Cancer Recurrence: An In-Depth Comparative Analysis of Invasive-Front Prognostic Markers

This study aimed to compare common histologic markers at the invasive front of colon adenocarcinoma in terms of prognostic accuracy and interobserver agreement. Consecutive patients who underwent curative resection for stages I to III colon adenocarcinoma at a single institution in 2007 to 2014 were identified. Poorly differentiated clusters (PDCs), tumor budding, perineural invasion, desmoplastic reaction, and Crohn-like lymphoid reaction at the invasive front, as well as the World Health Organization (WHO) grade of the entire tumor, were analyzed. Prognostic accuracies for recurrence-free survival (RFS) were compared, and interobserver agreement among 3 pathologists was assessed. The study cohort consisted of 851 patients. Although all the histologic markers except WHO grade were significantly associated with RFS (PDCs, tumor budding, perineural invasion, and desmoplastic reaction: P

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Using Synthetic CT for Partial Brain Radiation Therapy: Impact on Image Guidance

Publication date: Available online 6 April 2018
Source:Practical Radiation Oncology
Author(s): Eric D. Morris, Ryan G. Price, Joshua Kim, Lonni Schultz, M. Salim Siddiqui, Indrin Chetty, Carri Glide-Hurst
PurposeRecent advancements in synthetic computed tomography (synCTs) from MRI data have made MR-only treatment planning feasible in brain, although synCT performance for IGRT is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT.MethodsTen brain cancer patients (12 lesions, 7 post-surgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and FLAIR datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index (OI), Dice similarity coefficient (DSC), and Jaccard index (JI). Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2D-2D rigid registrations using normalized mutual information (NMI). Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3D vector difference. 1490 rigid registrations were assessed.ResultsDRR agreements in anterior–posterior and lateral views for OI, DSC, and JI were>0.95. NMI results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (p<0.05). The population average absolute shifts were 0.77±0.58mm and 0.76±0.59mm for CT and synCT, respectively for all axes/quadrants. 3D vectors were<2mm in 77.7±10.8% and 76.5±7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in post-surgical cases (vector displacements >2mm in affected quadrants).ConclusionDRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in post-surgical settings.



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Laparoscopic Assessment to Determine the Likelihood of Achieving Optimal Cytoreduction in Patients Undergoing Primary Debulking Surgery for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Objective: The objective of this study was to evaluate the safety and efficacy of laparoscopic assessment to determine the likelihood of achieving optimal cytoreduction (OC) in patients undergoing primary debulking surgery (PDS) for ovarian cancer. Methods: All patients who underwent diagnostic laparoscopy and PDS at our institution from January 2008 to December 2013 were identified. We determined the likelihood of achieving optimal cytoreduction by laparoscopic assessment based on tumor site, pattern of spread, and disease burden. Sensitivity was defined as the number of patients who achieved optimal cytoreduction after laparoscopic assessment divided by the number of patients with disease deemed resectable by laparoscopy. Results: We identified 55 patients during study period. Twenty-one of the 55 patients (38%) were early stage disease. Six (10.9%) patients had disease deemed unresectable and 49 (89.1%) had disease deemed resectable at the time of laparoscopy. OC was achieved in 48 of 49 (97.9%) patients. The sensitivity of laparoscopy in predicting OC was 98% (95% confidence interval, 89.3%-99.9%). The operation was completed laparoscopically in 23 of 49 patients (47%); in 26 of 49 (53%), PDS was performed by laparotomy. There were no port site metastases reported. The rate of postoperative complications was 16%. With a median follow-up of 30 months, the median overall survival was not reached and the 75th percentile for overall survival was 37 months. Conclusions: Laparoscopy was shown to have a high sensitivity in predicting OC and is a feasible tool in triaging patients with ovarian cancer. Laparoscopy is not associated with adverse surgical outcomes. V.A. and A.K. contributed equally. The authors declare no conflicts of interest. Reprints: Linus Chuang, MD, Division of Gynecologic Oncology, Icahn School of Medicine at Mount Sinai, 1176 Fifth Avenue, 1st Floor, New York, NY 10029. E-mail: linus.chuang@mountsinai.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of Concomitant Urologic Intervention on Clinical Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Introduction: The impact of concomitant urologic procedures (UPs) on perioperative and long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is uncertain. Methods: In total, 935 consecutive CRS/HIPEC procedures were performed between 1996 and 2016 in Sydney, Australia. Among these, 73 (7.8%) involved concomitant UP. The association of concomitant UP with 21 perioperative outcomes and overall survival was assessed using univariate and multivariate analyses. Results: In-hospital mortality was 1.8%. Patients requiring UP were more likely to require transfusion of ≥5 units of red blood cells (P=0.031) and have a complete cytoreduction (79% vs. 60%, P

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“Free or Perforator-Pedicled Propeller Flaps in Lower Extremity Reconstruction: Defining the Coverage Failure”: Response

J reconstr Microsurg
DOI: 10.1055/s-0038-1639601

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

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Sternal Reconstruction with the Omental Flap—Acute and Late Complications, Predictors of Mortality, and Quality of Life

J reconstr Microsurg
DOI: 10.1055/s-0038-1629918

Background The omental flap is a reliable flap for the coverage of sternal defects. However, little is known about the predictors of mortality and the long-term outcome in such patients. Methods We, therefore, performed a retrospective study from 2002 to 2013, including all patients that underwent sternal reconstruction with the omental flap. Results A total of 50 patients was identified and mean follow-up was 3.8 years. Patient data was collected from the charts and 14 patients were available for telephone interviews. The majority of patients suffered from deep sternal wound infections. There was no complete flap loss and an overall success rate was 96%. In-hospital mortality was 14% and overall survival over follow-up was 50%. Significant predictors of mortality were age > 65, American Society of Anesthesiologists' status, defect size, prolonged ventilation, and the need for tracheotomy. Postoperative quality of life was reduced compared with other cohorts, especially with regard to bodily function. Pain was also a major problem for most patients along with herniation. Conclusion The omental flap is a safe option even in patients with severe comorbidities. However, based on the data in this study, we would recommend the omental flap as a reserve option rather than first-line treatment for sternal defects.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Proximal versus Distal Recipient Vessels in Lower Extremity Reconstruction: A Retrospective Series and Systematic Review

J reconstr Microsurg
DOI: 10.1055/s-0037-1621746

Background Recipient vessels proximal to the zone of injury have traditionally been preferred for lower extremity reconstruction. However, more recent data have shown mixed outcomes when performing anastomoses distal to the zone of injury. We investigated the impact of recipient vessel location on free flap outcomes. Methods Retrospective review (1979–2016); 312 soft tissue free flaps for open tibia fractures met inclusion criteria. Flap characteristics and perioperative outcomes were examined. Systematic review identified articles evaluating anastomosis location and flap outcomes; pooled data analysis was performed. Results More anastomoses were performed proximal to the zone of injury (80.7%) than distal (19.3%). Distal anastomoses were not associated with increased take back rates (19.6%) compared with proximal (23.8%) anastomoses (p = 0.356). Regression analysis comparing proximal and distal anastomoses found no difference in partial flap failures (7.4% vs 11.9%; p = 0.978) or total flap failures (9.3% vs 9.3%; p = 0.815) when controlling for the presence of arterial injury, flap type, and time from injury to coverage. Systematic review yielded 11 articles with 1,245 proximal and 127 distal anastomoses for comparison. Pooled analysis (p = 0.58) and weighted comparative analysis (p = 0.39) found no difference in flap failure rates between proximal and distal groups. Conclusion Our results are congruent with the current lower extremity literature and demonstrate no difference in perioperative complication rates between anastomoses performed proximal or distal to the zone of injury. These findings suggest that anastomotic location choice should be based primarily on recipient vessel quality/flow and ease of access/exposure rather than orientation relative to the zone of injury.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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All-In-One Surgical Guide: A New Method For Cranial Vault Resection And Reconstruction

Great precision is required for craniofacial surgery, and computer-aided design (CAD) methods may be used to plan surgery before it is performed. In this study, three-dimensional (3D)-printed cutting guides are used to match computer models with surgical procedures. We describe a novel method of computer-aided surgery for autologous cranioplasty that includes a new strategy for generating and using cutting guides. These guides may be used not only for osteotomies, but also for many other steps in the surgical procedure.

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Dr. Michael Baldwin named UW Magnuson Scholar

Dr. Michael Baldwin, a 2015 University of Washington dental graduate who is also completing work on a PhD in oral biology at the UW, has been named a UW Magnuson Scholar for 2018-19.

The post Dr. Michael Baldwin named UW Magnuson Scholar appeared first on UW School of Dentistry.

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A Preliminary Examination of Concussion Knowledge by Collegiate Athletes and Non-Athletes

Purpose

Concussions affect various populations, including collegiate athletes and non-athletes. The purpose of this study was to compare collegiate varsity athletes, recreational athletes, and non-athletes' knowledge of concussion definition, symptoms, and support services available following injury. Preferred method of concussion education delivery was also examined.

Method

We surveyed 306 current college students using an online survey system. The survey included free recall and forced-choice question formats. Quantitative analyses were used to analyze results and compare responses among groups.

Results

Collegiate athletes and non-athletes demonstrate incomplete knowledge of concussion definition, related symptoms, and professionals involved in postinjury management. Varsity athletes rated self-knowledge of concussion parameters significantly higher than the other groups (p < .001), though few significant differences in actual knowledge levels were observed. Overall, respondents reported having the highest preference for concussion education delivered by medical professionals.

Conclusion

Knowledge concerning concussion is incomplete in the collegiate population. Varsity athletes' exposure to formal education did not result in higher knowledge levels compared with other groups. Further examination of concussion educational delivery models' effect on change in concussion-related behavior in this population is warranted.

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School-Based Speech-Language Pathologists' Perspectives on Diagnostic Decision Making

Purpose

This study used a structured open interview approach to elicit information from school-based speech-language pathologists (SLPs) regarding their assessment practices for children with suspected language impairment.

Method

Phone interviews were conducted with 39 school-based SLPs who were employed across the United States. The interviews explored assessment topics related to assessment tool selection and rationale and the integration of assessment data to determine treatment eligibility.

Results

The results of this study suggest that SLPs use both standardized testing and informal testing for their diagnostic procedures. Standardized testing appears to be the tool that drives diagnostic decisions regarding eligibility and severity. Informal measures, such as parent/teacher interviews and language sampling, were used by school-based SLPs to gather information regarding naturalistic language use; however, they seem less important in the diagnostic decision-making process. Also, SLPs reported completing language sample transcription and analysis in real time while interacting with a child.

Conclusions

School-based SLPs appear to rely on the results from standardized testing when determining treatment eligibility for children with language impairment. The reliance on standardized testing appears to be driven by institutional policies. We discuss the potential impact of federal/state/district guidelines on diagnostic decisions and consider the research-to-practice gap.

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Grammatical Abilities in Young Cochlear Implant Recipients and Children With Normal Hearing Matched by Vocabulary Size

Purpose

This study sought to expand understanding of the impact of cochlear implantation on grammatical acquisition by comparing young children who have vocabularies of comparable size. Two research questions were investigated: (a) Do young cochlear implant (CI) recipients have grammatical skills comparable to those of children with normal hearing (NH) matched by spoken vocabulary size? (b) Do these groups show associations between vocabulary size and grammatical measures?

Method

The participants included 13 CI recipients at 24 months postactivation (chronological ages = 33–60 months; M = 44.62) and 13 children with NH between 27 and 30 months old (M = 20.69). The 2 groups were matched by their vocabulary size. Four grammatical outcomes were analyzed from the MacArthur Communicative Development Inventory (Fenson, Marchman, Thal, Dale, & Reznick, 2007) and 20-min language samples: (a) grammatical complexity, (b) mean length of utterances, (c) tense marker total, and (d) productivity scores.

Results

The 2 groups showed comparable grammatical skills across the 4 measures. Consistently significant associations between vocabulary size and grammatical outcomes were found in the CI group, with fewer associations in the NH group.

Conclusions

The 2 groups showed similar grammatical abilities. The young CI recipients appeared to be following a typical pattern of linguistic development.

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Illustrating a Supports-Based Approach Toward Friendship With Autistic Students

Purpose

The present clinical focus article describes and illustrates 3 key elements of a supports-based approach to enhancing friendship with autistic students.

Method

In comparison to the predominant skills-based approach, we highlight 3 key elements of a supports-based approach to social interaction for autistic children and youth. We then offer descriptive details of the activity-based music program as an illustrative example of a program that integrated all 3 elements of a supports-based approach. Specifically, we designed an activity-based music program to enhance social interaction among a 7-year-old autistic student and 4 of his nonautistic peers.

Results

We focused on 3 key elements of a supports-based approach for enhancing peer interaction: (a) focusing on participation in a shared activity, (b) encouraging flexible use of multiple communicative resources, and (c) supporting egalitarian interaction.

Conclusion

A supports-based approach presents a theoretically distinct and viable alternative to a skills-based approach in the design of social supports for autistic students and their peers.

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The Impact of Individual Differences on a Bilingual Vocabulary Approach for Latino Preschoolers

Purpose

The purpose of this study was twofold: First, we replicated in a new sample our previous findings that a culturally and linguistically responsive (CLR) bilingual approach for English vocabulary instruction for preschool Latino dual language learners was effective. Subsequently, we investigated whether the positive effect of CLR instruction varies as a function of individual child characteristics, including baseline vocabulary levels and gender.

Method

Using a randomized pretest–posttest follow-up group design, we first replicated our previous study (N = 42) with a new sample by randomly assigning 35 Spanish-speaking Latino preschoolers to a CLR bilingual group or an English-only group. The preschoolers received small-group evidence-informed shared readings targeting 30 English words 3 times a week for 5 weeks in their preschools. Vocabulary outcomes were measured using both standardized and researcher-developed measures. We subsequently conducted further studies with the combined sample size of 77 children to examine the variability in intervention effects related to child gender and baseline vocabulary levels.

Results

The direct replication study confirmed findings of our earlier work suggesting that the CLR bilingual approach promoted greater gains in L1 and L2 vocabulary than in an English-only approach. The extension studies revealed that the effect of the CLR bilingual vocabulary approach on English and Spanish vocabulary outcomes was not impacted by gender or vocabulary status at baseline.

Conclusion

This study provides additional evidence of the benefits of strategically combining L1 and L2 for vocabulary instruction over an English-only approach. Our findings also suggest that preschool Latino dual language learners can benefit from a bilingual vocabulary instructional approach regardless of gender or baseline vocabulary levels in L1.

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Comprehension of Degraded Speech Matures During Adolescence

Purpose

The aim of the study was to compare comprehension of spectrally degraded (noise-vocoded [NV]) speech and perceptual learning of NV speech between adolescents and young adults and examine the role of phonological processing and executive functions in this perception.

Method

Sixteen younger adolescents (11–13 years), 16 older adolescents (14–16 years), and 16 young adults (18–22 years) listened to 40 NV sentences and repeated back what they heard. They also completed tests assessing phonological processing and a variety of executive functions.

Results

Word-report scores were generally poorer for younger adolescents than for the older age groups. Phonological processing also predicted initial word-report scores. Learning (i.e., improvement across training times) did not differ with age. Starting performance and processing speed predicted learning, with greater learning for those who started with the lowest scores and those with faster processing speed.

Conclusions

Degraded (NV) speech comprehension is not mature even by early adolescence; however, like adults, adolescents are able to improve their comprehension of degraded speech with training. Thus, although adolescents may have initial difficulty in understanding degraded speech or speech as presented through hearing aids or cochlear implants, they are able to improve their perception with experience. Processing speed and phonological processing may play a role in degraded speech comprehension in these age groups.

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Effect of a domiciliary facial cooling system on generic quality of life after removal of mandibular third molars

Publication date: Available online 5 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A.N. Beech, S. Haworth, G.J. Knepil
To evaluate quality of life (QoL) and patients' perceptions of a domiciliary facial cooling system (Hilotherm^®, Hilotherapy UK Ltd, Coventry, UK), we asked 30 patients to complete a paper-based EQ-5D-3L QoL questionnaire (EuroQol Group 1990, Rotterdam, The Netherlands) each day for seven days after the removal of mandibular third molars. They were returned by 14 of the 20 patients who had not used the system and by all 10 who had. Patients aged between 18 and 25 who had their teeth removed in outpatients (in accordance with National Institute for Health and Care Excellence guidelines) under general anaesthesia (American Association of Anesthesiologists (ASA) class I or II) and did not smoke, were included. They were all treated by the same surgeon in the day surgery unit of a district general hospital. Patients found the system helpful and easy to use. They had no complications, their QoL was significantly improved (p<0.001), and the time taken to return to normal activities was reduced. The Hilotherm^® domiciliary facial cooling system is safe and helps in the management of postoperative pain and swelling. Our findings confirm recently published meta-analyses that show the effectiveness of hilotherapy after facial surgery.



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Clinicopathological features of squamous cell carcinoma of the oral cavity and oropharynx in young patients

Publication date: Available online 5 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R.C.-P. Martinez, H.P. Sathasivam, B. Cosway, V. Paleri, S. Fellows, J. Adams, M. Kennedy, R. Pearson, A. Long, P. Sloan, M. Robinson
Our aim was to examine the clinicopathological features of squamous cell carcinoma (SCC) of the oral cavity and oropharynx in a group of young patients who were dignosed during a 15-year period (2000–2014). Patients' clinical details, risk factors, and survival were obtained from medical records. Formalin-fixed, paraffin-embedded, tissue was tested for high-risk human papillomavirus (HPV). The results were compared with those of a matching group of older patients. We identified 91 patients who were younger than 45 years old, and the 50 youngest patients were studied in detail. The male:female ratio was 2:1, with more tumours located in the oral cavity than in the oropharynx (35 compared with 15). HPV-related SCC was restricted to the oropharynx. When matched for site, stage and HPV status, five-year overall survival was similar in young and matched older patients (log-rank test, p=0.515). Our findings suggest that young patients with oral SCC have a disease profile similar to that of older patients with the condition. It is plausible that prognostic information generally available for oral cancers is applicable to young patients with the disease.



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“Run-through” training at specialist training year 1 and uncoupled core surgical training for oral and maxillofacial surgery in the United Kingdom: a snapshot survey

Publication date: Available online 5 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M. Garg, J. Collyer, D. Dhariwal
Training in oral and maxillofacial surgery (OMFS) in the UK has undergone considerable changes during the last 10years, and "core" surgical training has replaced "basic" surgical training. In 2014 a pilot "run-through" training programme from specialist training year one (ST1)-ST7 was introduced to facilitate early entry into the speciality. Run-through training guarantees that a trainee, after a single competitive selection process and satisfactory progress, will be given training that covers the entire curriculum of the speciality, whereas uncoupled training requires a second stage of competitive recruitment after the first one (for OMFS only) or two years of "core" training to progress to higher specialty training.The first two years of run-through training (ST1-ST2) are the same as for core surgical training. Dual-qualified maxillofacial aspirants and those in their second degree course are curious to know whether they should go for the uncoupled core surgical training or the run-through programme in OMFS. The General Medical Council (GMC) has now agreed that run-through training can be rolled out nationally in OMFS. To assess the two pathways we used an online questionnaire to gain feedback about the experience from all OMFS ST3 and run-through trainees (ST3/ST4) in 2016–2017. We identified and contacted 21 trainees, and 17 responded, including seven run-through trainees. Eleven, including five of the run-through trainees, recommended the run-through training programme in OMFS. Six of the seven run-through trainees had studied dentistry first. The overall mean quality of training was rated as 5.5 on a scale 0–10 by the 17 respondents. This survey gives valuable feedback from the current higher surgical trainees in OMFS, which will be useful to the GMC, Health Education England, OMFS Specialist Advisory Committee, and those seeking to enter higher surgical training in OMFS.



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Readability of Patient-Reported Outcome Measures in Adult Audiologic Rehabilitation

Purpose

The purpose of this study was to examine the readability of published patient-reported outcome measures (PROMs) designed for use in adult audiologic rehabilitation. The readability results were compared with the readability levels recommended for health information by health literacy experts.

Method

Reading grade levels were calculated using the Flesch–Kincaid Grade Level Formula (Flesch, 1948), Gunning Fog Index (Gunning, 1952), Simple Measure of Gobbledygook (McLaughlin, 1969), and FORCAST (Caylor, Sticht, Fox, & Ford, 1973) readability formulas for 10 published PROMs. Descriptive statistics were computed across the different PROM sections: instructions, items, response scale, and overall contents of the measure directed toward respondents.

Results

The majority of the PROM sections exceeded the 6th grade reading level recommended by health literacy experts, regardless of the formula applied. All PROM sections exceeded the 6th grade reading level when calculated according to the FORCAST formula, the most appropriate readability formula for use with a nonnarrative text format, such as PROMs.

Conclusions

When developing or reevaluating PROMs designed for use in adult audiologic rehabilitation, researchers should consider ways to improve the readability of their measure, as poor readability may affect the validity of the empirical data collected using the PROM. Additionally, the adequate readability of audiologic PROMs is required if patient/family-centered care values are to be adhered to within the field of adult audiologic rehabilitation.

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Urban versus Rural Residency and Allergy Prevalence among Adult Women: Iowa Women's Health Study

The association between residence and allergy has been well studied in children living on a farm; however, studies of this association in late adulthood are lacking.

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Patient-specific pre-contouring of osteosynthesis plates for mandibular reconstruction: Using a three-dimensional key printed solution

Publication date: Available online 6 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): J. Kraeima, H.H. Glas, M.J.H. Witjes, K.P. Schepman
PurposeIn mandibular reconstructive surgery, the osteosynthesis plates require contouring according to the patients' individual anatomical situation. These plates are frequently contoured around a three-dimensional (3D) printed model. However, the translation to the actual patient can introduce inaccuracies and unwanted rotations in the condyles and mandibular ramus, due to malpositioning of the pre-contoured plate.Materials and MethodsThis article describes an easy-access method for exact translation of the pre-contoured plate to the patient's mandible. This is done by using 3D printed guides that allow pre-drilling of screw holes in both the contour model and the patients' mandible. The accuracy of the Key Printed Solution was analysed by comparing the anatomical landmarks on both the 3D planned and post-operative models.ResultsThe method was applied to 4 cases. All landmarks were identified on both the 3D planning and post-operative computed tomographic data. This showed an average deviation of 1.0 mm between planning and the post-operative result. The inter-observer variation was 0.6 mm (intra-class correlation, 0.75).ConclusionThis article presents an easy-to-use method for pre-bending the osteosynthesis plate and subsequent accurate translation of the intended contour with corresponding screw hole locations. The method was proved to be accurate and time-efficient.



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sAssessment of Regional Asymmetry of the Face Before and After Surgical Correction of Unilateral Cleft Lip

Publication date: Available online 6 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Dhelal Al-Rudainy, Xiangyang Ju, Steve Stanton, Felicity V. Mehendale, Ashraf Ayoub
This study was carried out on 26 unilateral cleft lip and palate (UCLP) cases with mean age 3.6 ± 0.7 months.3D facial images were captured for each infant 2–3 days before the repair of cleft lip and at 4 months following surgery at a mean age of 8.2 ± 1.8 months, using a stereophotogrammetry imaging system. An iterative closest point (ICP) algorithm was used to superimpose the 3D facial model to its mirror image using VRMesh software. After the superimposition, the face model was divided into seven anatomical regions. Asymmetry of the entire face and of the anatomical regions was calculated by measuring the absolute distances between the 3D facial surface model and its mirror image. Colour maps were used to illustrate the patterns and magnitude of the facial asymmetry before and after surgery. There were significant decreases in the asymmetry scores for the nose, upper lip and the cheeks as a result of the surgical repair of cleft lips. Surgery did not change the magnitude of the asymmetry scores for the lower lip and chin.The main outcome of the findings of this innovative study is to inform the required surgical refinement of primary repair of cleft lip in order to minimise facial asymmetry and to guide secondary corrective surgery. We have presented a sensitive tool that could be used for comparative analysis of lip repair at various cleft centres.



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All-In-One Surgical Guide: A New Method For Cranial Vault Resection And Reconstruction

Publication date: Available online 6 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Alessandro Tel, Fabio Costa, Salvatore Sembronio, Andrea Lazzarotto, Massimo Robiony
IntroductionGreat precision is required for craniofacial surgery, and computer-aided design (CAD) methods may be used to plan surgery before it is performed. In this study, three-dimensional (3D)-printed cutting guides are used to match computer models with surgical procedures. We describe a novel method of computer-aided surgery for autologous cranioplasty that includes a new strategy for generating and using cutting guides. These guides may be used not only for osteotomies, but also for many other steps in the surgical procedure.Materials and MethodsPreoperatively, anatomical data were imported into a CAD package and used for virtual surgical planning (VSP). Cutting guides were designed after considering how to integrate all the surgical steps. Models of the microplates and micro-screws were also made. Surgical guides were exported and printed, and preoperative simulations using a replica of the patient's skull established the sequence of steps. The accuracy of the procedure was evaluated postoperatively using computed tomography (CT) scans.ResultsIn every patient examined, the all-in-one surgical-guide system was able to automate the many steps in the procedure and dramatically decreased the duration of surgery. The experimental guide enhanced every phase of surgery, including excising the lesion, and harvesting, positioning, and fixing the graft. In each step, precision was enhanced and the outcome corresponded with the VSP.ConclusionsThe few previous reports on cutting guides used in cranioplasty generally describe the use of separate guides for dismantling and reconstruction. The ability to perform more surgical sequences using a single tool can improve surgical accuracy. Clearly there is no single perfect surgical guide; however, effective surgical-design strategies should be used to build the best approach to each procedure.



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Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules

Head &Neck, EarlyView.


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Tinnitus, Depression, Anxiety, and Suicide in Recent Veterans: A Retrospective Analysis

Objectives: The purpose of this project was to investigate whether there is an association between tinnitus diagnosis and suicide and whether depression and anxiety strengthen that association. Given that tinnitus is the top service–connected disability among U.S. Veterans (Veterans Benefits Administration, 2016) and that suicide among Veterans has been occurring at a higher frequency as compared with community suicide rates (Hoffmire et al., 2015), the possible associations between tinnitus and suicide will be explored. Co-occurring physical conditions also will be examined to determine if they increase the risk of suicide in the context of tinnitus. Design: Administrative health care data related to Operations Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) were used to identify Veterans who accessed the Veterans Administration (VA) health care system from January 1, 2002, to December 31, 2011. Veterans who were deceased as of December 2011 were identified using the National Death Index (NDI) files. Tinnitus cases were followed until either they were deceased or to the end of the study period. The International Classification of Diseases 9th Revision Clinical Modification (ICD-9-CM) codes were used to identify all conditions and diseases. As per mortality research standards, International Classification of Diseases 10th Revision (ICD-10) codes were used to identify cause of death. Results: Of 769,934 OEF/OIF/OND Veterans receiving VA care January 2002 to December 2011, 15% (n =116,358) were diagnosed with tinnitus. Of these Veterans diagnosed with tinnitus, 21% were also diagnosed with depression, another 8% with anxiety, and another 17% with both depression and anxiety. Fifty-four percentage were identified as having tinnitus without depression or anxiety. Among individuals with tinnitus, 41.9% had co-occurring hearing loss. Suicide rates were lower among Veterans with tinnitus than Veterans without tinnitus. Co-occurring diagnoses of mental-health conditions did not significantly increase the risk of suicide. Conclusions: The study results do not confirm clinical and anecdotal reports that tinnitus could be related to suicide among Veterans. However, tenets from rehabilitation psychology suggest that the onset of chronic impairment or disability does not predict an individual's subsequent psychological states; other personal attributes may be more influential. Health care professionals, such as audiologists and psychologists, should be cognizant of the associations between tinnitus and mental health issues and be prepared to address the psychological needs of individuals who have tinnitus. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal's Web site (www.ear-hearing.com). ACKNOWLEDGEMENTS: This material is the result of work supported with resources and the use of facilities at the VA Portland Healthcare System and the support of the VHA Office of Patient Care Services, Post Deployment Health Services. The authors acknowledge the help that Dr. Robert Bossarte provided to the first two authors as they were starting this research study. Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. All authors contributed equally to this work. E.M. and C.J. conducted the literature review, and E.M. wrote most of the introduction and discussion sections. D.D. and C.W. ran the data analyses and wrote most of the Methods section, including the results, and created the tables. A.S. reviewed and discussed the data analyses with D.D. and C.W. All authors not only discussed the results and their implications but also edited the article throughout its evolution. There are no conflicts of interest to report. Received June 27, 2017; accepted January 23, 2018. Address for correspondence: Erin Martz, VA Portland Healthcare System, Bldg. 6, Room 114A, 3710 SW U.S. Veterans Hospital Rd, Portland, OR 97239. E-mail: rehabilityoregon@gmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Evaluation of Speed and Accuracy of Next-Generation Auditory Steady State Response and Auditory Brainstem Response Audiometry in Children With Normal Hearing and Hearing Loss

Objectives: The first objective of this study was to compare the predicted audiometric thresholds obtained by auditory steady state response (ASSR) and auditory brainstem response (ABR) in infants and toddlers when both techniques use optimal stimuli and detection algorithms. This information will aid in determining the basis for large discrepancies in ABR and ASSR measures found in past studies. The hypothesis was that advancements in ASSR response detection would improve (lower) thresholds and decrease discrepancies between the thresholds produced by the two techniques. The second objective was to determine and compare test times required by the two techniques to predict thresholds for both ears at the 4 basic audiometric frequencies of 500, 1000, 2000, and 4000 Hz. Design: A multicenter clinical study was implemented at three university-based children's hospital audiology departments. Participants were 102 infants and toddlers referred to the centers for electrophysiologic testing for audiometric purposes. The test battery included wideband tympanometry, distortion-product otoacoustic emissions, and threshold measurements at four frequencies in both ears using ABR and ASSR (randomized) as implemented on the Interacoustics Eclipse systems with "Next-Generation" ASSR detection and FMP analysis for ABR. Both methods utilized narrow band CE-Chirp stimuli. Testers were trained on a specialized test battery designed to minimize test time for both techniques. Testing with both techniques was performed in one session. Thresholds were evaluated and confirmed by the first author and correction factors were applied. Test times were documented in system software. Results: Corrected thresholds for ABR and ASSR were compared by regression, by the Bland–Altman technique and by matched pairs t tests. Thresholds were significantly lower for ASSR than ABR. The ABR–ASSR discrepancy at 500 Hz was 14.39 dB, at 1000 Hz was 10.12 dB, at 2000 Hz was 3.73 dB, and at 4000 Hz was 3.67 dB. The average test time for ASSR of 19.93 min (for 8 thresholds) was found to be significantly lower (p

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Toward Optimizing VEMP: Calculating VEMP Inhibition Depth With a Generic Template

Objectives: Cervical vestibular evoked myogenic potentials (cVEMP) indirectly reveal the response of the saccule to acoustic stimuli through the inhibition of sternocleidomastoid muscle electromyographic response. VEMP inhibition depth (VEMPid) is a recently developed metric that estimates the percentage of saccular inhibition. VEMPid provides both normalization and better accuracy at low response levels than amplitude-normalized cVEMPs. Hopefully, VEMPid will aid in the clinical assessment of patients with vestibulopatholgy. To calculate VEMPid a template is needed. In the original method, a subject's own cVEMP was used as the template, but this method can be problematic in patients who do not have robust cVEMP responses. We hypothesize that a "generic" template, created by assembling cVEMPs from healthy subjects, can be used to compute VEMPid, which would facilitate the use of VEMPid in subjects with pathological conditions. Design: A generic template was created by averaging cVEMP responses from 6 normal subjects. To compare VEMPid calculations using a generic versus a subject-specific template, cVEMPs were obtained in 40 healthy subjects using 500, 750, and 1000 Hz tonebursts at sound levels ranging from 98 to 123 dB peSPL. VEMPids were calculated both with the generic template and with the subject's own template. The ability of both templates to determine whether a cVEMP was present or not was compared with receiver operating characteristic curves. Results: No significant differences were found between VEMPid calculations using a generic template versus using a subject-specific template for all frequencies and sound levels. Based on the receiver operating characteristic curves, the subject-specific and generic template did an equally good job at determining threshold. Within limits, the shape of the generic template did not affect these results. Conclusions: A generic template can be used instead of a subject-specific template to calculate VEMPid. Compared with cVEMP normalized by electromyographic amplitudes, VEMPid is advantageous because it averages zero when there is no sound stimulus and it allows the accumulating VEMPid value to be shown during data acquisition as a guide to deciding when enough data has been collected. ACKNOWLEDGMENTS: The authors thank audiologists Heidi Leonard and Mark Sanders for their help with threshold determination. This study was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102), and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. This work was presented as a poster at the Association of Research in Otolaryngology Midwinter meeting in Baltimore, MD (February 11-15, 2017). This study was approved by the Human Studies Committee of the Massachusetts Eye and Ear Infirmary. Protocol number: 13-097H. Principal Investigator: Steven D. Rauch. The authors have no conflicts of interest to disclose. Address for correspondence: John J. Guinan Jr., 243 Charles Street, Boston, MA 02114, USA. E-mail: John_Guinan@meei.harvard.edu Received November 1, 2017; accepted February 10, 2018. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Comparisons of IQ in Children With and Without Cochlear Implants: Longitudinal Findings and Associations With Language

Objectives: To make longitudinal comparisons of intelligence quotient (IQ) in children with cochlear implants (CIs) and typical hearing peers from early in development to the school-age period. Children with additional comorbidities and CIs were also evaluated. To estimate the impact of socioeconomic status and oral language on school-age cognitive performance. Design: This longitudinal study evaluated nonverbal IQ in a multicenter, national sample of 147 children with CIs and 75 typically hearing peers. IQ was evaluated at baseline, prior to cochlear implantation, using the Bayley Scales of Infant and Toddler Development and the Leiter International Performance Scale. School-age IQ was assessed using the Wechsler Intelligence Scales for Children. For the current study, only the Perceptual Reasoning and Processing Speed indices were administered. Oral language was evaluated using the Comprehensive Assessment of Spoken Language. Results: Children in the CI group scored within the normal range of intelligence at both time points. However, children with additional comorbidities scored significantly worse on the Processing Speed, but not the Perceptual Reasoning Index. Maternal education and language were significantly related to school-age IQ in both groups. Importantly, language was the strongest predictor of intellectual functioning in both children with CIs and normal hearing. Conclusion: These results suggest that children using cochlear implants perform similarly to hearing peers on measures of intelligence, but those with severe comorbidities are at-risk for cognitive deficits. Despite the strong link between socioeconomic status and intelligence, this association was no longer significant once spoken language performance was accounted for. These results reveal the important contributions that early intervention programs, which emphasize language and parent training, contribute to cognitive functioning in school-age children with CIs. For families from economically disadvantaged backgrounds, who are at-risk for suboptimal outcomes, these early intervention programs are critical to improve overall functioning. ACKNOWLEDGMENTS: This work was supported by grant R01DC004797 from NIH. Dr. Cejas is on the AG Bell Board of Directors, MED-EL pediatric advisory board, and consults with ASHA, and has a research agreement and consultancy with Advanced Bionics. Ms. Mitchell has received support from Advanced Bionics through a research contract to her institution. The other authors do not have any conflicts of interest with regard to this study. Address for correspondence: Ivette Cejas, PhD, The Barton G Kids Hear Now Cochlear Implant Family Resource Center, University of Miami Ear Institute, 1120 NW 14th Street, CRB 5th Floor, Miami, FL 33136. E-mail: icejas@med.miami.edu Received June 23, 2017; accepted February 5, 2018. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Fine‐needle aspiration of tubulocystic renal cell carcinoma

Diagnostic Cytopathology, EarlyView.


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Overexpression of WD repeat domain 5 associates with aggressive clinicopathological features and unfavorable prognosis in head neck squamous cell carcinoma

Journal of Oral Pathology &Medicine, EarlyView.


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Microsatellite instability associated with durable complete response to PD-L1 inhibitor in head and neck squamous cell carcinoma

Survival of recurrent or metastatic Head and Neck Squamous Cell Carcinoma patients (R/M-HNSCC) is still short. The median survival time of patients treated by platinum-based chemotherapy plus cetuximab is 10.1 months [1]. Recently, nivolumab, a PD-1 inhibitor, demonstrated a gain in overall survival in pretreated R/M-HNSCC in comparison to standard treatment [2]. Other checkpoint inhibitors targeting PD-1 (pembrolizumab) or PD-L1 (atezolizumab, durvalumab) also showed activity with objective response rates ranging between 13 and 18% [3–5].

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Distinct Acoustic Features and Glottal Changes Define Two Modes of Singing in Peking Opera

Publication date: Available online 6 April 2018
Source:Journal of Voice
Author(s): Gelin Li, Haiqing Li, Qian Hou, Zhen Jiang
ObjectiveWe aimed to delineate the acoustic characteristics of the Laodan and Qingyi role in Peking Opera and define glottis closure states and mucosal wave changes during singing in the two roles.MethodsThe range of singing in A4 (440 Hz) pitch in seven female Peking Opera singers was determined using two classic pieces of Peking Opera. Glottal changes during singing were examined by stroboscopic laryngoscope. The fundamental frequency of /i/ in the first 15 seconds of the two pieces and the /i/ pitch range were determined. The relative length of the glottis fissure and the relative maximum mucosal amplitude were calculated.ResultsQingyi had significantly higher mean fundamental frequency than Laodan. The long-term average spectrum showed an obvious formant cluster near 3000 Hz in Laodan versus Qingyi. No formant cluster was observed in singing in the regular mode. Strobe laryngoscopy showed complete glottal closure in Laodan and incomplete glottal closure in Qingyi in the maximal glottis closure phase. The relative length of the glottis fissure of Laodan was significantly lower than that of Qingyi in the singing mode. The relative maximum mucosal amplitude of Qingyi was significantly lower than that of Laodan.ConclusionThe Laodan role and the Qingyi role in Peking Opera sing in a fundamental frequency range compatible with the respective use of da sang (big voice) and xiao sang (small voice). The morphological patterns of glottal changes also indicate that the Laodan role and the Qingyi role sing with da sang and xiao sang, respectively.



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Patient-specific pre-contouring of osteosynthesis plates for mandibular reconstruction: Using a three-dimensional key printed solution

Publication date: Available online 6 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): J. Kraeima, H.H. Glas, M.J.H. Witjes, K.P. Schepman
PurposeIn mandibular reconstructive surgery, the osteosynthesis plates require contouring according to the patients' individual anatomical situation. These plates are frequently contoured around a three-dimensional (3D) printed model. However, the translation to the actual patient can introduce inaccuracies and unwanted rotations in the condyles and mandibular ramus, due to malpositioning of the pre-contoured plate.Materials and MethodsThis article describes an easy-access method for exact translation of the pre-contoured plate to the patient's mandible. This is done by using 3D printed guides that allow pre-drilling of screw holes in both the contour model and the patients' mandible. The accuracy of the Key Printed Solution was analysed by comparing the anatomical landmarks on both the 3D planned and post-operative models.ResultsThe method was applied to 4 cases. All landmarks were identified on both the 3D planning and post-operative computed tomographic data. This showed an average deviation of 1.0 mm between planning and the post-operative result. The inter-observer variation was 0.6 mm (intra-class correlation, 0.75).ConclusionThis article presents an easy-to-use method for pre-bending the osteosynthesis plate and subsequent accurate translation of the intended contour with corresponding screw hole locations. The method was proved to be accurate and time-efficient.



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sAssessment of Regional Asymmetry of the Face Before and After Surgical Correction of Unilateral Cleft Lip

Publication date: Available online 6 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Dhelal Al-Rudainy, Xiangyang Ju, Steve Stanton, Felicity V. Mehendale, Ashraf Ayoub
This study was carried out on 26 unilateral cleft lip and palate (UCLP) cases with mean age 3.6 ± 0.7 months.3D facial images were captured for each infant 2–3 days before the repair of cleft lip and at 4 months following surgery at a mean age of 8.2 ± 1.8 months, using a stereophotogrammetry imaging system. An iterative closest point (ICP) algorithm was used to superimpose the 3D facial model to its mirror image using VRMesh software. After the superimposition, the face model was divided into seven anatomical regions. Asymmetry of the entire face and of the anatomical regions was calculated by measuring the absolute distances between the 3D facial surface model and its mirror image. Colour maps were used to illustrate the patterns and magnitude of the facial asymmetry before and after surgery. There were significant decreases in the asymmetry scores for the nose, upper lip and the cheeks as a result of the surgical repair of cleft lips. Surgery did not change the magnitude of the asymmetry scores for the lower lip and chin.The main outcome of the findings of this innovative study is to inform the required surgical refinement of primary repair of cleft lip in order to minimise facial asymmetry and to guide secondary corrective surgery. We have presented a sensitive tool that could be used for comparative analysis of lip repair at various cleft centres.



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All-In-One Surgical Guide: A New Method For Cranial Vault Resection And Reconstruction

Publication date: Available online 6 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Alessandro Tel, Fabio Costa, Salvatore Sembronio, Andrea Lazzarotto, Massimo Robiony
IntroductionGreat precision is required for craniofacial surgery, and computer-aided design (CAD) methods may be used to plan surgery before it is performed. In this study, three-dimensional (3D)-printed cutting guides are used to match computer models with surgical procedures. We describe a novel method of computer-aided surgery for autologous cranioplasty that includes a new strategy for generating and using cutting guides. These guides may be used not only for osteotomies, but also for many other steps in the surgical procedure.Materials and MethodsPreoperatively, anatomical data were imported into a CAD package and used for virtual surgical planning (VSP). Cutting guides were designed after considering how to integrate all the surgical steps. Models of the microplates and micro-screws were also made. Surgical guides were exported and printed, and preoperative simulations using a replica of the patient's skull established the sequence of steps. The accuracy of the procedure was evaluated postoperatively using computed tomography (CT) scans.ResultsIn every patient examined, the all-in-one surgical-guide system was able to automate the many steps in the procedure and dramatically decreased the duration of surgery. The experimental guide enhanced every phase of surgery, including excising the lesion, and harvesting, positioning, and fixing the graft. In each step, precision was enhanced and the outcome corresponded with the VSP.ConclusionsThe few previous reports on cutting guides used in cranioplasty generally describe the use of separate guides for dismantling and reconstruction. The ability to perform more surgical sequences using a single tool can improve surgical accuracy. Clearly there is no single perfect surgical guide; however, effective surgical-design strategies should be used to build the best approach to each procedure.



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