OtoRhinoLaryngology News: 11/23/17

Πέμπτη 23 Νοεμβρίου 2017

Coincidence of pollen season with the first fetal trimester together with early pet exposure is associated with sensitisation to cat and dog allergens in early childhood: a Finnish population-based study

Abstract

Background

Children whose 11^th fetal week falls in pollen season (spring) reportedly have an increased risk of sensitisation to food allergens. No such finding has been reported for pet allergens.

Objective

The aim of the study was to 1) evaluate the incidence of pet (dog and cat) sensitisation according to the season of the 11^th fetal week and 2) whether the association between pet exposure and respective sensitisation is modified by the coincidence of the 11^th fetal week with pollen season.

Methods

The study population comprised all children (born between 2001 and 2006) in the province of South Karelia, Finland (N=5920). Their data of IgE and skin prick tests to pet allergens (N=538) were collected from patient records and linked with questionnaire data on pet exposure.

Results

The seasonal incidence peak of cat sensitisation was observed in children whose 11^th fetal week occurred in June (7.4%) and that of dog sensitisation in April (3.8%) and June (4.7%). The relative rate (RR) for cat sensitisation was 2.92 (95% CI 1.40-6.08) in children with cat exposure alone, 8.53 (4.07−17.86) in children with cat and fetal pollen exposures, and 0.61 (0.20−1.83) in children exposed to pollen alone, compared with children without these exposures. The respective RRs for dog sensitisation were 2.17 (1.13-4.19), 4.40 (2.19−8.83) and 1.65 (0.77−3.53).

Conclusions and clinical relevance

Coincidence of the first fetal trimester with pollen season strengthens the association between pet exposure and respective sensitisation. Pollen exposure at early pregnancy may deviate immune system towards Th2 type reactivity promoting development of specific allergy in case allergen exposure occurred. Therefore, primary prevention of allergic diseases may need to begin during early pregnancy.

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Correction to: Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.

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Severe infantile onset developmental and epileptic encephalopathy caused by mutations in autophagy gene WDR45

Summary

Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta-propeller protein-associated neurodegeneration (BPAN). BPAN is characterized by adolescent onset dementia and dystonia; 66% patients have seizures. We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. We identified 3/655 patients with DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6 truncations, 1 missense); all were female. Six presented with DEE and 1 with early onset focal seizures and profound regression. Median seizure onset was 12 months, 6 had multiple seizure types, and 5/7 had focal seizures. Three patients had magnetic resonance susceptibility-weighted imaging; blooming was noted in the globus pallidi and substantia nigra in the 2 older children aged 4 and 9 years, consistent with iron accumulation. We show that de novo pathogenic variants are associated with a range of developmental and epileptic encephalopathies with profound developmental consequences.

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Inhibition of monoacylglycerol lipase terminates diazepam-resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet

Summary

Objective

Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA). Inhibiting of monoacylglycerol lipase modulates synaptic activity and neuroinflammation, 2 mediators of excessive neuronal activation underlying seizures. We studied the effect of a potent and selective irreversible MAGL inhibitor, CPD-4645, on SE that was refractory to diazepam, its neuropathologic sequelae, and the mechanism underlying the drug's effects.

Methods

Diazepam-resistant SE was induced in adult mice fed with standard or ketogenic diet or in cannabinoid receptor type 1 (CB1) receptor knock-out mice. CPD-4645 (10 mg/kg, subcutaneously) or vehicle was dosed 1 and 7 h after status epilepticus onset in video–electroencephalography (EEG) recorded mice. At the end of SE, mice were examined in the novel object recognition test followed by neuronal cellloss analysis.

Results

CPD-4645 maximal plasma and brain concentrations were attained 0.5 h postinjection (half-life = 3.7 h) and elevated brain 2-AG levels by approximately 4-fold. CPD-4645 administered to standard diet–fed mice progressively reduced spike frequency during 3 h postinjection, thereby shortening SE duration by 47%. The drug immediately abrogated SE in ketogenic diet–fed mice. CPD-4645 rescued neuronal cell loss and cognitive deficit and reduced interleukin (IL)-1β and cyclooxygenase 2 (COX-2) brain expression resulting from SE. The CPD-4645 effect on SE was similar in mice lacking CB1 receptors.

Significance

MAGL represents a novel therapeutic target for treating status epilepticus and improving its sequelae. CPD-4645 therapeutic effects appear to be predominantly mediated by modulation of neuroinflammation.

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Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women

Abstract

Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC).

We followed 77,288 female American nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥ 0.8mm or Clark's level of IV and V according to history of NMSC.

We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05–2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55-1.37)), Breslow thickness ≥0.8mm (0.85 (0.59-1.21)) and Clark's levels IV and V (0.81(0.52-1.24)).

Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of subsequent melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from subsequent melanoma. This article is protected by copyright. All rights reserved.

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Bevacizumab in Combination with Different Platinum-based Doublets in the First-line Treatment for Advanced Nonsquamous Non-small-cell Lung Cancer: A Network Meta-Analysis

Abstract

Platinum-based doublet chemotherapy with or without bevacizumab is the standard treatment for untreated advanced nonsquamous non-small-cell lung cancer (NS-NSCLC). However, adding bevacizumab to chemotherapies other than paclitaxel-carboplatin is, though widely applied clinically, largely unjustified due to the lack of head-to-head data. We performed a Bayesian network meta-analysis (NMA) to address this important issue. Data of 8548 patients from 18 randomized controlled trials (RCTs) receiving six treatments including taxane-platinum (Taxane-Pt), gemcitabine-platinum (Gem-Pt), pemetrexed-platinum (Pem-Pt), taxane-platinum + bevacizumab (Taxane-Pt+B), gemcitabine-platinum + bevacizumab (Gem-Pt+B) and pemetrexed-platinum + bevacizumab (Pem-Pt+B) were incorporated into the analyses. Direct and indirect evidence of overall survival (OS) and progression-free survival (PFS) were synthesized at the hazard ratio (HR) scale and evidence of objective response rate (ORR) and serious adverse events (SAE) were synthesized at the odds ratio (OR) scale. Taxane-Pt+B showed significant advantages in OS (HR=0.79, P<0.001), PFS (HR=0.54, P<0.001) and ORR (OR=2.7, P<0.001) over Taxane-Pt with comparable tolerability (OR=3.1, P=0.08). Gem-Pt+B showed no OS benefit compared to any other treatment. No significant differences were detected between Pem-Pt+B and Pem-Pt in four outcomes. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B were ranked the first and second respectively. In conclusion, in the first-line treatment for advanced NS-NSCLC, Taxane-Pt and Gem-Pt are the most and least preferable regimens to be used with bevacizumab, respectively. Adding bevacizumab to Pem-Pt remains unjustified because it fails to improve efficacy or tolerability. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B are the best and second-best treatment for this population. This article is protected by copyright. All rights reserved.

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Tank bromeliads capture Saharan dust in El Yunque National Forest, Puerto Rico

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Dana L. Royer, Kylen M. Moynihan, Carolyn Ariori, Gavin Bodkin, Gabriela Doria, Katherine Enright, Rémy Hatfield-Gardner, Emma Kravet, C. Miller Nuttle, Lisa Shepard, Timothy C.W. Ku, Suzanne O'Connell, Phillip G. Resor
Dust from Saharan Africa commonly blows across the Atlantic Ocean and into the Caribbean. Most methods for measuring this dust either are expensive if collected directly from the atmosphere, or depend on very small concentrations that may be chemically altered if collected from soil. Tank bromeliads in the dwarf forest of El Yunque National Forest, Puerto Rico, have a structure of overlapping leaves used to capture rainwater and other atmospheric inputs. Therefore, it is likely that these bromeliads are collecting in their tanks Saharan dust along with local inputs. Here we analyze the elemental chemistry, including rare earth elements (REEs), of tank contents in order to match their chemical fingerprint to a provenance of the Earth's crust. We find that the tank contents differ from the local soils and bedrock and are more similar to published values of Saharan dust. Our study confirms the feasibility of using bromeliad tanks to trace Saharan dust in the Caribbean.

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Changes in oxidative potential of soil and fly ash after reaction with gaseous nitric acid

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Ying Zhan, Matthew Ginder-Vogel, Martin M. Shafer, Yinon Rudich, Michal Pardo, Itzhak Katra, David Katoshevski, James J. Schauer
The goal of this study was to examine the impact of simulated atmospheric aging on the oxidative potential of inorganic aerosols comprised primarily of crustal materials. Four soil samples and one coal fly ash sample were artificially aged in the laboratory through exposure to the vapor from 15.8 M nitric acid solution for 24 h at room temperature. Native and acid-aged samples were analyzed with a cellular macrophage and acellular dithionthreitol assays to determine oxidative potential. Additionally, the samples were analyzed to determine the concentration of 50 elements, both total and the water-soluble fraction of these elements by Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICMS) and crystalline mineral composition using X-ray Diffraction (XRD). The results show that reactions with gaseous nitric acid increase the water-soluble fraction of many elements, including calcium, iron, magnesium, zinc, and lead. The mineral composition analysis documented that calcium-rich minerals present in the soils (e.g., calcite) are converted into different chemical forms, such as calcium nitrate (Ca(NO3)2). The nitric acid aging process, which can occur in the atmosphere, leads to a 200–600% increase in oxidative potential, as measured by cellular and acellular assays. This laboratory study demonstrates that the toxic effects of aged versus freshly emitted atmospheric dust may be quite different. In addition, the results suggest that mineralogical analysis of atmospheric dust may be useful in understanding its degree of aging.

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PAHs in Chinese atmosphere Part I: Concentration, source and temperature dependence

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Wan-Li Ma, Li-Yan Liu, Hong-Liang Jia, Meng Yang, Yi-Fan Li
The study on atmospheric polycyclic aromatic hydrocarbons (PAHs) in China has regional and global significance to understand the large scale atmospheric transport of PAHs. In this study, 16 US EPA priority PAHs were analyzed in more than 500 pairs of gas and particle phases samples, which were collected on the same schedule on a weekly basis from August 2008 to July 2009 at 11 urban sites (6 northern cities and 5 southern cities) across China. The average concentration was 239 ± 329 ng/m³ and 165 ± 164 ng/m³ for the northern cities and the southern cities, respectively. Different seasonal variations of atmospheric PAHs were observed between northern cities and southern cities, which were mainly caused by the different temperature effects in winter. Identified by principal component analysis, coal combustion and vehicle exhaust were the major sources of atmospheric PAHs in northern and southern cities of China, respectively. The temperature dependences of atmospheric PAHs were also different, which were caused by the different influences of temperature on identified sources. To our knowledge, this is the first comprehensive study to report the difference with concentrations, seasonal variations, sources and temperature dependences of atmospheric PAHs between northern cities and southern cities in China.

Graphical abstract

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The adverse effects of gas-burning CHP systems on the local air quality

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Javad Jazaeri, Mahdi Pahlevani
One of the benefits of the combined heat and power (CHP) systems is reducing greenhouse gases (GHG) in the national level. These systems are installed in the close vicinity of local communities and their pollution can directly affect the local environment. This paper studies the adverse environmental effects of a 2 MW gas-burning CHP (GB-CHP) system in a residential community in Mashhad, Iran. We compare the amount of CO2 and NOx emissions from the GB-CHP with the conventional choice of supplying electricity from the central power plants and heat from the locally installed boilers. The results show that the GB-CHP system increases local CO2 and NOx emissions by approximately two and six times, respectively. The NOx emission is increased from 3.1 tonnes to 18.7 tonnes. The CO2 emission increases from 3623 tonnes to 7238 tonnes. Furthermore, we use Gaussian Dispersion model to estimate the concentration of these emissions in the local area using the weather conditions of the most polluted times of the previous year. The results show that for a 3-meter stack, the maximum concentration of CO2 and NOx are 14.8 mg/m3 and 38.1 μg/m3, respectively. Our analysis shows that increasing the height of the GB-CHP stack from 3 meters to 10 meters reduces the concentration by 40%.

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Consistency and applicability of parameterization schemes for the size-resolved aerosol activation ratio based on field measurements in the North China Plain

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Jiangchuan Tao, Chunsheng Zhao, Nan Ma, Ye Kuang
Parameterization of the size-resolved particle activation ratio (AR) is useful for the prediction and analysis of the cloud condensation nuclei (CCN) number concentration (NCCN). Critical issues for the application of AR parameterizations in models are (1) the consistency of the different parameterization schemes in terms of fitting AR curves and (2) the applicability of the estimate of NCCN under different aerosol conditions. These issues are discussed in this study based on summertime measurements of the size-resolved AR in the North China Plain. By comparing parameterized AR curves, variations in the fitting parameters and application to NCCN calculations, the consistency of the three existing parameterization schemes is confirmed. Based on an analysis using representative AR fitting parameters, the method commonly used to calculate NCCN with a fixed AR was found to be accurate, except during periods affected by strong black carbon (BC) emissions or new particle formation (NPF) events. The NCCN value was overestimated by approximately 10% when BC aerosol emissions were abundant and deviated from the 1:1 line by 15% during NPF events. The bias of the calculated NCCN due to these significant emission or aerosol production events cannot be eliminated by using the appropriate representative fitting parameters. Under these circumstances, accurate prediction of NCCN requires real-time aerosol hygroscopicity data based on CCN measurements. This research furthers our understanding of the relationship between aerosol cloud activation and aerosol spectra.

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Analysis of patterns in the concentrations of atmospheric greenhouse gases measured in two typical urban clusters in China

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Lixin Liu, Pieter P. Tans, Lingjun Xia, Lingxi Zhou, Fang Zhang
China is the largest emitter of greenhouse gases, and urban clusters play an essential role in China's carbon emissions because of the country's unbalanced economic development. In this paper, the discrete air sample measurements of atmospheric CO2, CH4, and CO during the period between 2007 and 2013 from Shangdianzi (SDZ) station in Jing-Jin-Ji (JJJ) region and Linan (LAN) station in Yangtze River Delta (YRD) region, respectively, are presented and characterized. By backward trajectory cluster analysis, the low background CO2 mole fraction and similar long-term trends with Waliguan global station (WLG) were observed at SDZ because most of the air masses originate mostly from remote clean terrestrial areas in the north with limited information of anthropogenic emissions. But the background CH4 and CO are influenced mainly by ruminants and rice field emission from the surrounding regions and urban cluster emission in the JJJ region, which lead to the higher CH4 and CO in summer at SDZ. Whereas, the CO2, CH4 and CO background values observed at LAN are higher by the combined effects of long-distance atmospheric transportation from Northern and Central China and urban clusters emission from the YRD region. The observed polluted data at SDZ and LAN are all strongly affected by regional and local anthropogenic emissions, which lead to the higher GHGs concentrations compared to the background data. However, because the air mass transportation from the north is weak in winter and no winter heating is required and vegetation photosynthesis is still stronger in the south of China, the CO2 concentration at LAN is lower than that at SDZ in autumn and winter. The polluted CO value at SDZ is found considerably higher than that at LAN, especially in spring and winter. By analyzing the correlations of observed regional enhanced values of CO2, CH4 and CO at the two stations, we find the significant correlation between them, which means they may share the common-source of anthropogenic emissions from the regional fossil fuel and biomass burning in cold season. Moreover, the high coal-consumption proportion with the low CO2 emissions factors, and much biomass burning with low combustion efficiency in JJJ region lead to the higher slope values of △CO2 and △CO in spring and winter at SDZ and considerably higher than that at LAN. The results can provide a further understanding of regional/local features of atmospheric GHGs under the influence of human activities in the urban clusters in China.

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Public willingness to pay for urban smog mitigation and its determinants: A case study of Beijing, China

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Kangyin Dong, Xiangang Zeng
With the deteriorating air pollution in the urban areas of China, particularly the unprecedentedly high levels of smog, public demand for clean air is increasing. This study examines the values of public willingness to pay (WTP) for three smog mitigation scenarios in the urban areas of Beijing and investigates their determinants by employing the contingent valuation method (CVM) and interval regression model. The empirical results suggest that more than 80% of the respondents is willing to pay for smog mitigation. Respondents' WTP rises with an increasing smog mitigation percentage, and the amount of WTP for 30%, 45%, and 60% smog mitigation, respectively, is 615.13 CNY, 716.34 CNY, and 914.49 CNY, accounting for 0.55%, 0.64%, and 0.82% of their annual income. In contrast with other cities, the ratio of WTP to income in Beijing seems to situate inside a relatively moderate range. Moreover, respondents' knowledge, risk perception, and attitude toward government are positively and significantly correlated with their WTP, and other determinants such as age, health condition, and annual income also significantly affect the value of WTP. We further recommend several important policy implications, which offer new evidence for developing specific policies to tackle smog pollution.

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Cause-specific mortality in HPV+ and HPV− oropharyngeal cancer patients: insights from a population-based cohort

Abstract

Identifying the causes of death in head and neck cancer patients can optimize follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause-specific mortality in a population-based cohort of patients with OPSCC. Patients who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern Denmark were included in the study. Causes of death were collected through medical files and the Danish National Cause of Death registry. Deaths were grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3) cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative incidence of death and specific causes of death were determined using risk analysis. At follow-up, 723 (47.5%) patients had died. The median time to and cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing secondary screening and prevention strategies for late toxicity and mortality are major goals in managing the treatment of these patients.

Identifying cause of death in oropharyngeal cancer patients may aid in optimizing follow-up and therapeutic strategies, but studies stratified on HPV status is lacking. We report cause-specific mortality in a population-based cohort of oropharyngeal cancer patients from 2000 to 2014.

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Prevalencia de alteraciones en el complejo estilohioideo y tonsilolitos en la tomografía computarizada de haz cónico realizada en individuos con fisura labiopalatina

Publication date: Available online 23 November 2017
Source:Acta Otorrinolaringológica Española
Author(s): Eymi Valery Cazas-Duran, Izabel Regina Fischer Rubira-Bullen, Otávio Pagin, Bruna Stuchi Centurion-Pagin
Introducción y objetivosLos tonsilolitos y alteraciones en el complejo estilohioideo pueden presentar similar sintomatología a otras de diferente etiología. Los individuos con fisura labiopalatina describen similares síntomas en razón de las repercusiones anatómicas propias de esta anomalía. El objetivo de este estudio fue determinar la prevalencia de alteraciones del complejo estilohioideo y tonsilolitos en exámenes de tomografía computarizada de haz cónico en individuos con fisura labiopalatina.MétodosSegún criterios de inclusión y exclusión fueron analizadas 66 tomografías de 2.794 tomografías, en el software i- Cat visión ® con índice Kappa 0,8 intraexaminador.ResultadosLa prevalencia total de osificación del complejo estilohioideo incompleto en individuos con fisura labiopalatina fue de 66,6%, la prevalencia de estos hallazgos en el género femenino fue de 75% y 61,9% en el género masculino. La prevalencia total de tonsilolitos fue de 7,5%.ConclusiónEs de relevancia constatar en el informe radiológico la presencia de la calcificación del complejo estilo-hioideo y tonsilolitos. Debido a la proximidad anatómica y similar sintomatología clínica con otras alteraciones orofaciales presentes en los individuos con fisura labiopalatina, haciendo énfasis en individuos con fisura labiopalatina del género femenino, pacientes con fisura tipo transformen incisivo y posforamen incisivo por presentar mayor prevalencia. Conocer más sobre la morfometría anatómica de individuos con fisura labiopalatina coadyuva relevantemente en la elección de conductas clínicas y calidad de vida de estos pacientes, teniendo presente que la fisura labiopalatina es una de las anomalías más comunes.Introduction and objectivesTonsilloliths and abnormal stylohyoid complex may have similar symptoms to others of different aetiology. Individuals with cleft lip and palate describe similar symptoms because of the anatomical implications that are peculiar to this anomaly. The aim of this study was to determine the prevalence of abnormal stylohyoid complex and tonsilloliths on cone beam computed tomography in individuals with cleft lip and palate.MethodsAccording to the inclusion and exclusion criteria, 66 CT scans out of of 2,794 were analysed, on i- Cat ® vision software with 0.8 index Kappa intra-examiner.ResultsThe total prevalence of ossification of the incomplete stylohyoid complex in individuals with cleft lip and palate was 66.6%; the prevalence of these findings in females was 75% and 61.9% in males. The total prevalence of tonsilloliths was 7.5%.ConclusionIt is important to ascertain calcification of the stylohyoid complex and tonsilloliths in the radiological report, due to the anatomical proximity and similarsymptomatology to other orofacial impairments inindividuals with cleft lip and palate, focusing on females with oral cleft formation, patients with incisive trans foramen cleft and incisive post foramen cleft because they are more prevalent. Greater knowledge of the anatomical morphometry of individuals with cleft lip and palate greatly contributes towards the selection of clinical behaviours and the quality of life of these patients, since cleft lip and palateis one of the most common anomalies.

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Reductions in prostatic doses are associated with less acute morbidity in patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for focal therapy

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Adam Ferro, Hee Joon Bae, Gayane Yenokyan, Yi Le, Todd McNutt, Omar Mian, Carol Gergis, Chloe Haviland, Theodore L. DeWeese, Daniel Y. Song
PurposeInterest in prostate dose reduction or focal treatment exists due to expected reductions in treatment morbidity. Prior analyses have not generally corroborated relationships between prostate or urethral dose and urinary toxicity after brachytherapy, but such analyses have been performed on cohorts all receiving the same prescribed dose. We analyzed patients treated to differing prescription doses to assess acute urinary morbidity with dose reduction.Methods and MaterialsPatients treated with Pd-103 to either 125 Gy or 90–100 Gy were compared using the International Prostate Symptom Score (IPSS) at 1-month postimplant. Patients in the 90–100 Gy cohort began external beam radiation therapy after their 1-month assessment; thus, toxicities were measured before contribution from external beam radiation therapy. Patient/treatment characteristics were compared to verify subgroup homogeneity. Dose and change in IPSS 1 month after treatment were assessed using a multivariate linear regression model.ResultsOne hundred ninety-one and 41 patients were treated with 125 Gy versus 90–100 Gy, respectively. Preimplant and postimplant prostate volumes and initial IPSS were similar between groups. Higher prescription dose and increased pretreatment IPSS were independent predictors of increased 1-month IPSS. In addition, every 10 percentage point additional prostate volume receiving a given dose was associated with increase in IPSS after treatment for the same level of pretreatment IPSS.ConclusionLower prescription dose and decreased volume of high-dose regions to the prostate correlated with reduced acute urinary morbidity after brachytherapy. Our findings suggest that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy.

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The impact of adjuvant vaginal brachytherapy in women with Stage II uterine endometrioid carcinoma: Results of a National Cancer Database analysis

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Joon K. Lee, Ahmed I. Ghanem, Ankit Modh, Charlotte Burmeister, Omar Mahmoud, G. Larry Maxwell, Mohamed A. Elshaikh
PurposeTo report survival outcomes in women with Stage II uterine endometrioid carcinoma who received adjuvant radiation therapy (RT) without chemotherapy using the National Cancer Database.Methods and MaterialsThe National Cancer Database was queried for women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma who underwent hysterectomy followed by adjuvant RT without chemotherapy. The χ² tests were performed to compare differences in outcome by type of adjuvant RT (external beam radiation therapy [EBRT] alone, vaginal brachytherapy [VBT] alone, or combination of EBRT and VBT). Overall survival (OS) was assessed by Kaplan–Meier and log-rank tests. Univariate and multivariate analyses were performed to identify predictors of OS.ResultsWe identified 2681 women. Simple hysterectomy was performed on 2261 women (84%). Adjuvant EBRT, VBT, and combination RT were administered to 27%, 36%, and 37%, respectively. There was a statistically significant difference in OS by modality of adjuvant RT (p = 0.01) favoring women who received VBT alone or in combination with EBRT. The 5-year OS was 80%, 87%, and 83% for women who received EBRT, VBT, and combination RT, respectively (p = 0.001). On multivariate analysis, old age, African-American race, no or fewer number of examined lymph nodes, and higher tumor grade were independent predictors of worse OS. RT modality did not sustain its independent prognostic significance as a predictor of OS.ConclusionsIn this nationwide hospital-based study of women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma, adjuvant VBT alone provided excellent survival outcomes and may be a reasonable adjuvant RT modality for properly selected women with adequate lymph node dissection and low-grade tumors.

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Plesiobrachytherapy for chest wall recurrences of breast cancer after mastectomy and radiotherapy for breast cancer

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Nadia Besson, Christophe Hennequin, Sophie Guillerm, Ingrid Fumagalli, Valentine Martin, Sophie Michaud, Luis Texeira, Laurent Quero
PurposeThe purpose of the study was to evaluate the results of high-dose-rate plesiobrachytherapy for local relapse after mastectomy and radiotherapy in terms of both local control and survival.MethodsWe reviewed retrospectively 43 patients who experienced a chest wall relapse of breast cancer after local excision (22 patients) or not (21 patients). Patients were treated with an individually designed mold with four to six fractions of 3–6 Gy high-dose-rate brachytherapy, two fractions per week. Mean total dose was 24 Gy.ResultsAfter surgical resection, the 3- and 5-year local control rates were 80% and 73%, respectively. For nonresectable patients, the overall response rate was 86%, and the 3-year infield local control and chest wall local control were 51% and 26%, respectively. The 5-year survival rate was 50.5% for the whole population, 62% after surgery, and 45.4% for irresectable patients. Acute Grade 2 or 3 toxicity occurred in 43% of the patients, resolving in a few days. Two patients had a local necrosis lasting 3 to 7 months. Late toxicity was observed in 5 patients.ConclusionsHigh-dose-rate plesiobrachytherapy is a simple outpatient technique to treat chest wall local relapse of breast cancer. As a reirradiation technique, its tolerance is acceptable. This technique may obtain long-term local control after incomplete surgery; in case of nonresectable disease, a high response rate was observed, which might improve the quality of life of these patients.

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Tongue Pressure Production and Submental Surface Electromyogram Activities During Tongue-Hold Swallow with Different Holding Positions and Tongue Length

Abstract

Our previous study regarding the tongue-hold swallow (THS) demonstrated that the tongue-to-palate contact during THS could be influenced by the maximum tongue protrusion length (MTPL) of individual subjects, resulting in two different patterns of pressure generation. The present study further analyzed the influence of MTPL on the tongue pressure production along with submental surface electromyography (sEMG) during THS, in order to establish an index to better control THS effects. Tongue pressure using a sensor sheet system and concurrent submental sEMG activities were measured during swallowing tasks in 18 healthy young adults. Task conditions comprised THS at two different degrees of tongue protrusion and dry swallow. Tongue pressures and sEMG activities were compared among three task conditions, and correlations of MTPL with tongue pressure were also investigated. Additionally, a ROC curve was used to find a cut-off value for MTPL to predict changes (increases and decreases) in tongue pressure during THS. The duration and the amount of submental muscle activity increased concurrently during THS. Two trends were shown on the change in tongue pressure at the posterior-circumferential part of the hard palate during THS compared to dry swallow; the maximal magnitude and the integrated value of tongue pressure increased in some subjects, while these values decreased in others. Thirty-two millimeters was found to be the cut-off value of MTPL, which distinguishes increase/decrease pattern of tongue pressure with sensitivities of 60.0–85.7%. The present finding suggests that more reliable THS effects should be attainable using MTPL to set the tongue-hold position.

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Stroke-like migraine attacks after radiation therapy: A misnomer?

Summary

Objective

To understand the frequency of electrographic and clinical seizures in patients with stroke-like migraine attacks after radiation therapy (SMART), and determine whether SMART warrants comprehensive electroencephalographic (EEG) monitoring and aggressive seizure management.

Methods

We searched our magnetic resonance brain imaging report database for all patients between January 2013 and December 2015 for suspected SMART syndrome. Clinical inclusion criteria were further applied as follows: inpatient adults (>18 years of age) with history of cranial radiation presenting with acute neurologic deficits as primary admission reason who lacked evidence of recurrent or new brain malignancy, stroke, or infectious agents in cerebrospinal fluid. Six patients were identified. All 6 patients underwent prolonged video EEG monitoring as part of our standard protocol.

Results

All patients but 1 were found to have multiple or prolonged electrographic seizures consistent with status epilepticus during video EEG monitoring. Their neurological deficit and/or mental status change improved in parallel with resolution of the seizure activity.

Significance

SMART is likely a misnomer that underestimates the significance of seizures and status epilepticus in the pathophysiology and clinical presentation of the syndrome. Systematic continuous EEG monitoring and appropriate seizure management is warranted to reduce symptom duration and optimize clinical outcome.

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BAD knockout provides metabolic seizure resistance in a genetic model of epilepsy with sudden unexplained death in epilepsy

Summary

Metabolic alteration, either through the ketogenic diet (KD) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure-protective role of knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1^−/− model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1^−/− and Kcna1^−/−Bad^−/− double knockout mice to assess survival and seizure severity. We found that Kcna1^−/−Bad^−/− mice outlived Kcna1^−/− mice by approximately 2 weeks. Kcna1^−/−Bad^−/− mice also spent significantly less time in seizure than Kcna1^−/− mice on P24 and the day of death, showing that BadKO provides seizure resistance in a genetic model of chronic epilepsy.

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Immunological differences between insect venom-allergic patients with and without immunotherapy and asymptomatically sensitized subjects

Abstract

Background

Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings.

Methods

We included 77 asymptomatically-sensitized subjects, 85 allergic-patients with acute systemic sting reactions, and 61 allergic-patients currently treated with VIT. Levels of sIgE and sIgG₄ to bee and vespid venom, rApi-m-1 and rVes-v-5 were measured immediately after allergic sting-reactions or before sting-challenges and four weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT-inhibition and ELIFAB-assay.

Results

Median sIgG₄ levels were 96-fold higher in VIT patients (p<0.001) while sIgE/sIgG₄ ratios were consistently lower (p<0.001). The ELIFAB-assay was paralleled by low sIgE/sIgG₄ ratios in VIT-patients, showing markedly higher allergen-blocking capacity (p<0.001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG₄ levels were increased in allergic and asymptomatically-sensitized patients, but not in VIT-patients.

Conclusion

Immunological responses after stings varied in bee and vespid venom allergic patients. In patients under VIT, sIgE and sIgG₄ remained completely stable after sting-challenges. Monitoring VIT efficacy was only possible in vespid venom allergy and the sIgG₄ threshold for rVes-v-5 had the highest sensitivity to confirm tolerance. The BAT-inhibition test was the most reliable tool to confirm tolerance on an individual basis.

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Inactive lifestyles and sedentary behavior in persons with chronic aneurysmal subarachnoid hemorrhage: evidence from accelerometer-based activity monitoring

Aneurysmal subarachnoid hemorrhage (a-SAH) is a potential life-threatening stroke. Because survivors may be at increased risk for inactive and sedentary lifestyles, this study evaluates physical activity (PA) ...

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Impact of hydration and nutrition on personal performance in the clinical workplace

As clinicians we sometimes fail to look after ourselves at work. We often do not drink enough during the day or miss lunch breaks while caring for patients, and this can be particularly evident during an all-day operating list when procedures are long and complex. Some operating theatre staff do not even eat breakfast regularly. Inadequate intake of fluids or nutrition can impair performance, lead to tiredness and headaches, and may compromise both our own health and the care we provide to patients.

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Evaluation of the morphology of the genial tubercle using cone-beam computed tomography

The genial tubercle is a sharp projection of bone on the internal face of the mandible above the inferior border.1

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Is routine holistic assessment with a prompt list feasible during consultations after treatment for oral cancer?

The head and neck cancer Patient Concerns Inventory (PCI-HN) is a holistic, self-reported list of items that can help patients to disclose their needs and concerns during routine follow-up consultations. The aim of this study was to report how often it was used during the first three years of follow up after treatment for oral cancer, and the range of issues that were raised. The sample comprised consecutive patients treated over a three-year period with curative intent. All clinic attendances were reviewed until October 2015 or until patients had a recurrence, a subsequent primary, metastases, or were discharged home or to follow up at a peripheral hospital, or started palliative care.

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Corrigendum to “Schneider membrane thickness classification evaluated by cone-beam computed tomography and its importance in the predictability of perforation. Retrospective analysis of 200 patients” [Br. J. Oral Maxillofac. Surg. 54 (10) (December 2016) 1106–1110]

The authors regret the errors in the membrane thickness in Table 1 of the above referenced paper. The correct table can be found below.

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Tongue Pressure Production and Submental Surface Electromyogram Activities During Tongue-Hold Swallow with Different Holding Positions and Tongue Length

Abstract

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Management of hypogammaglobulinemia and recurrent infections in a chronic lymphocytic leukemia patient receiving ibrutinib

Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder characterized by the progressive accumulation of monoclonal and functionally incompetent lymphocytes; it also is the most common adult leukemia in Western countries.1 In CLL, hypogammaglobulinemia is the predominant inherent immune defect and is often further exacerbated by immunosuppressive treatment.2 Nevertheless, neither antibiotic prophylaxis nor prophylactic immunoglobulin (Ig) replacement therapy (IRT) is routinely recommended for CLL.

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Strawberry Gingivitis in Granulomatosis with Polyangiitis

Figure 1.

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Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

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MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer

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HER2 expression patterns in paired primary and metastatic endometrial cancer lesions

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Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy

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Removal of Cationic Dyes, Heavy Metal Ions, and CO 2 Capture by Adsorption on Mesoporous Silica HMS

Abstract

Mesoporous silica with wormhole framework structure (HMS-OH) and its amine-functionalized material (HMS-NH₂) were prepared through an electrically neutral assembly pathways, post-grafting process of 3-aminopropyltriethoxysilane (APTES), respectively. Their adsorption behaviors toward cationic dyes as well as heavy metal ions in aqueous system and the capture capacities for CO₂ molecules all have been investigated. As-synthesized HMS-OH showed a high removal efficiency and rapid sorption rate to cationic dyes because of large surface area and versatile pore structure. HMS-NH₂ exhibited better heavy metal ions and more CO₂ gas sorption capacities due to the intrinsic property of amine groups grafted on the surface. The adsorption isotherms of methylene blue (MB) onto HMS-OH, Cu(II) onto HMS-NH₂ were fitted with Langmuir model and kinetic processes followed well the pseudo-second order pattern. There results revealed that both HMS-OH and HMS-NH₂ had a potential application in the treatment of cationic dyes, heavy metal ions, and greenhouse gas CO₂.

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Prescription of secondary preventive drugs after ischemic stroke: results from the Malaysian National Stroke Registry

Evaluation of secondary stroke prevention in low and middle-income countries remains limited. This study assessed the prescription of secondary preventive drugs among ischemic stroke patients upon hospital dis...

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Sexsomnia: a diagnostic challenge, a case report

Marina Mioč, Elena Antelmi, Marco Filardi, Fabio Pizza, Francesca Ingravallo, Lino Nobili, Carlo Alberto Tassinari, Carlos H. Schenck and Giuseppe Plazzi have no financial relationships relevant to this article to disclose.

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A not so incidental finding in a 12 year old with sleepiness and headaches

A 12-year-old girl presented with headaches and hypersomnolence. Her bedtime was 10 PM with a latency of 30 minutes. Reported sleeping for 12-16 hours. Upon awakening she felt sleepy and tired but this resolved as the day went on. There were no symptoms of snoring, parasomnias, hypnagogic hallucinations, cataplexy, sleep paralysis, or restless legs. Physical and neurologic exams were normal. Polysomnography was normal. Brain MRI showed a pineal cyst (Figure 1). Salivary melatonin levels (ELISA/EIA calibrated range 0.78-50 pg/ml) were collected by the parent; at home, under regular bedtime conditions.

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Differences in rapid eye movement (REM) sleep abnormalities between posttraumatic stress disorder (PTSD) and major depressive disorder patients: REM interruption correlated with nightmare complaints in PTSD

The presence of repeated nightmares in posttraumatic stress disorder (PTSD) has been hypothesized as a dysfunction of rapid eye movement (REM) sleep, but there has been remarkably little agreement about the pathophysiology. This presents a deterrent to more effective treatments. REM sleep abnormalities including elevated REM density also have been replicated in major depressive disorder (MDD). The purpose of this study was to clarify the difference of REM sleep abnormalities between the two disorders for understanding the pathophysiology of sleep disturbances in PTSD.

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Elevated Tau and Interleukin-6 Concentrations in Adults with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas, resulting in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules, which along with amyloid beta (Aβ), is linked to neurodegenerative processes. We sought to determine if tau, and other biomarkers of inflammation, were related to OSA severity.Concentrations of tau, Aβ40 and Aβ42, c-reactive protein (CRP), TNF-α, interleukin (IL)-6, and IL-10 were measured in blood and compared in participants with moderate-severe (n=28), mild OSA (n=22), and healthy controls (n=24).

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HER2 expression patterns in paired primary and metastatic endometrial cancer lesions

HER2 expression patterns in paired primary and metastatic endometrial cancer lesions

HER2 expression patterns in paired primary and metastatic endometrial cancer lesions, Published online: 23 November 2017; doi:10.1038/bjc.2017.422

HER2 expression patterns in paired primary and metastatic endometrial cancer lesions

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MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer

MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer

MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer, Published online: 23 November 2017; doi:10.1038/bjc.2017.387

MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer

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Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study, Published online: 23 November 2017; doi:10.1038/bjc.2017.413

Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

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Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy

Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy

Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy, Published online: 23 November 2017; doi:10.1038/bjc.2017.414

Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy

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The Role of Affordable, Point-of-Care Technologies for Cancer Care in Low- and Middle-Income Countries: A Review and Commentary

As the burden of non-communicable diseases such as cancer continues to rise in low- and middle-income countries (LMICs), it is essential to identify and invest in promising solutions for cancer control and treatment. Point-of-care technologies (POCTs) have played critical roles in curbing infectious disease epidemics in both high- and low-income settings, and their successes can serve as a model for transforming cancer care in LMICs, where access to traditional clinical resources is often limited. The versatility, cost-effectiveness, and simplicity of POCTs warrant attention for their potential to revolutionize cancer detection, diagnosis, and treatment. This paper reviews the landscape of affordable POCTs for cancer care in LMICs with a focus on imaging tools, in vitro diagnostics, and treatment technologies and aspires to encourage innovation and further investment in this space.

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Sex-Dependent Effect of Metformin on Serum Prolactin Levels In Hyperprolactinemic Patients With Type 2 Diabetes: A Pilot Study

07-2017-0287-endo_10-1055-s-0043-122224-

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-122224

Background Metformin was found to reduce circulating levels of pituitary hormones. Objective The purpose of this study was to assess whether sex determines the effect of metformin on lactotroph secretory function. Methods The study population included 25 women and 12 men with mildly elevated serum prolactin levels (25–75 ng/mL). Because of concomitant type 2 diabetes, all participants were treated with metformin (3 g daily). Plasma levels of glucose and lipids, HOMA1-IR, serum levels of prolactin, thyrotropin and free thyroid hormones, as well as Jostel's, SPINA-GT and SPINA-GD indices were assessed at baseline and at the end of metformin treatment. Results The study completed 24 women and 11 men. At baseline, there were no significant differences in circulating levels of glucose and lipids, insulin sensitivity, hormones, Jostel's, SPINA-GT and SPINA-GD indices between women and men. In both men and women, metformin reduced fasting glucose levels and HOMA1-IR. However, only in women metformin decreased elevated prolactin levels and this effect correlated with an improvement insulin sensitivity, as well as with the impact on SPINA-GT. Conclusions The results of the study suggest that the effect of metformin on serum prolactin levels is sex-dependent.
[...]

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

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Editorial Board

Publication date: November 2017
Source:Journal of Oral Biosciences, Volume 59, Issue 4

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The temporospatial pattern of energy metabolism coordinates the interactions between the bones and other organ systems

Publication date: Available online 11 November 2017
Source:Journal of Oral Biosciences
Author(s): Ziyi Wang, Hiroshi Kamioka
BackgroundBones adapt to loads by changing their structure. This biomechanical interaction and the formation/maintenance of bones are orchestrated by three major cell types residing in the bones: osteoblasts, osteocytes, and osteoclasts. Recent findings suggest that, in addition to their biomechanical interactions, bones and other organ systems may also communicate biochemically.HighlightThis brief review will discuss the interaction between the bones and the nervous system, vasculature, muscle, and fat tissues, with an emphasis on the role of the energy metabolism in these interactions.ConclusionStudies on the connections between bones and other organ systems indicate the possible existence of a temporospatial pattern of energy metabolism through the cellular biorhythm and migration.

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Reviewer’s comment concerning “Lumbar total disc replacement: predictors for 8-year outcome” (by H. Furunes et al. [2017] Eur Spine J)

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Influence of enhanced recovery after surgery programs on laparoscopy-assisted gastrectomy for gastric cancer: a systematic review and meta-analysis of randomized control trials

Abstract

Background

This meta-analysis is aimed to evaluate the feasibility and safety of enhanced recovery after surgery (ERAS) programs in gastric cancer patients undergoing laparoscopy-assisted gastrectomy (LAG).

Methods

We performed a meta-analysis of randomized control trials involving either enhanced recovery after surgery (ERAS)/fast track surgery (FTS) for patients underwent LAG. EMBASE, Pubmed, Web of science, and Cochrane Library were searched. Primary outcomes included the length of postoperative hospital stay, cost of hospitalization, postoperative complications, and readmission rate.

Results

Five randomized control trials were eligible for analysis. There were 159 cases in FTS group and 156 cases in conventional care group. Compared with conventional care group, FTS group relates to shorter postoperative hospital stay (WMD − 2.16; 95% CI − 3.05 to − 1.26, P < 0.00001), less cost of hospitalization (WMD − 4.72; 95% CI − 6.88 to − 2.55, P < 0.00001), shorter time to first flatus (WMD − 9.72; 95% CI − 13.75 to − 5.81, P < 0.00001), lower level of C-reaction protein on postoperative days 3 or 4 (WMD − 19.66; 95% CI − 28.98 to − 10.34, P < 0.00001), higher level of albumin on postoperative day 4 (WMD 3.45; 95% CI 2.01 to 4.89, P < 0.00001), and postoperative day 7 (WMD 5.63; 95% CI 1.01 to 10.24, P = 0.02). Regarding postoperative complications, no significant differences were observed between FTS group and conventional care group (OR 0.63, 95% CI 0.37 to 1.09, P = 0.10). The readmission rate of FTS group was comparable to conventional care group (WMD 3.14; 95% CI 0.12 to 81.35, P = 0.49).

Conclusions

Among patients undergoing LAG, FTS is associated with shorter postoperative hospital stay, rapid postoperative recovery, and decreased cost without increasing complications or readmission rate. The combined effects of the two methods could further accelerate clinical recovery of gastric cancer patients.

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Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents

Ciska Verbaanderd, Hannelore Maes, Marco B Schaaf, Vikas P Sukhatme, Pan Pantziarka, Vidula Sukhatme, Patrizia Agostinis and Gauthier Bouche

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Oral tolerance modulates the skin transcriptome in mice with induced atopic dermatitis

Abstract

Defective gut immune reactions have been implicated in the development of atopic dermatitis (AD), whereas oral tolerance (OT), i.e., the immune unresponsiveness induced by oral antigen administration, protects mice against AD. To investigate this protective role of OT, the transcriptomic profiles of skin were obtained by RNA sequencing from mice that were epicutaneously sensitized, orally tolerized prior to epicutaneous sensitization, or neither (control). OT inhibited the upregulation of keratin- and allergic inflammation-associated genes that occurred in the epicutaneously sensitized group. Compared to the controls, mice that were orally tolerized and epicutaneously sensitized showed an upregulation of genes that regulate inflammation or keratinocyte differentiation. Knocking down two of those genes, SCGB1A1 and TSC22D3, upregulated Th2 inflammatory mediators and downregulated a cornified cell envelope-related gene. Based on our findings, OT may protect skin against allergic inflammation by promoting the expression of genes that regulate Th2 inflammatory responses and skin barrier function.

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An analysis of the risk factors of anastomotic stricture after esophagectomy

Abstract

Purpose

Anastomotic stricture after esophagectomy is a major cause of long-term morbidity and a poor quality of life. The aim of this study was to identify the risk factors for the development of anastomotic stricture after esophagectomy.

Methods

The study subjects were 213 patients who underwent esophagectomy for squamous cell carcinoma of the esophagus between 2012 and 2014. Anastomotic stricture was defined as stenosis at the site of anastomosis that required endoscopic dilation. Refractory stricture was defined as that requiring more than four sessions of dilations. Univariate and multivariate logistic regression analyses were used to identify the potential risk factors for the development of anastomotic stricture.

Results

In this retrospective study, 29 patients (13.6%) developed anastomotic stricture within a median period of 108 postoperative days and required a median of 2 dilations. Tumors located in the upper part of the esophagus (p = 0.004), the presence of cardiovascular disease (p = 0.024) and anastomotic leakage (p = 0.002) were identified as independent risk factors for the development of anastomotic stricture. The time to the diagnosis of refractory stricture (85 ± 33 days) was significantly shorter than that of non-refractory stricture (171 ± 22 days, p = 0.038).

Conclusions

Patients with squamous cell carcinoma in the upper esophagus with cardiovascular disease who develop postoperative anastomotic leakage should be carefully monitored to prevent the development of benign anastomotic stricture.

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Identifying accessible prognostic factors for breast cancer relapse: a case-study on 405 histologically confirmed node-negative patients

Abstract

Background

Histologically, node-negative breast cancer generally have a good prognosis. However, 10 to 30% of the cases present local relapses or metastasis. This group of people has high chances of remission if detected early. The aim of this study is to identify financial affordability for developing countries to adjust treatment.

Methods

We selected 405 patients with histologically confirmed node-negative breast cancer in our institution between January 2001 and December 2003. Patients with metastasis were excluded. The statistical analysis was conducted using SPSS ver. 18 (SPSS, Inc., Chicago, Illinois).

Results

The medial age was 51 years old. The medial tumor size was 35.4 mm. Clinically, 67.2% of the patients were staged cT2 and 63.2%, cN1i. Breast conservation was achieved in 41% of cases. In the histologic examination, the medial size was 30 mm. Grade III tumors were found in 50.1% of patients and positive hormonal receptors in 53.4%. The mean number of lymph nodes was 14. Eight patients had neoadjuvant chemotherapy. Adjuvant locoregional radiation and adjuvant chemotherapy were prescribed respectively in 70.6 and 64.4% of cases. 59.7% had adjuvant hormonal therapy. The follow-up showed 17.7% cases of relapse either locally or in a metastatic way in a mean time of 57.4 months. The disease-free survival at 5 years was 82.1%, and the overall survival for the same period was 91.5%.

The histologic tumor size and the grade and number of lymph node dissected were shown to be influencing the disease-free survival. Radiation therapy and hormone therapy showed improved disease-free survival and overall survival.

Conclusion

Our study found interesting results that may help personalize the treatment especially for patient living in underdeveloped countries, but further studies are needed to evaluate those and more accessible prognostic factors for a more accessible healthcare.

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Immunity and immunopathology in early human life

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Early life origin of type 1 diabetes

Abstract

Type 1 diabetes (T1D) is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing beta cells in the pancreatic islets in genetically susceptible subjects. The incidence of T1D has increased manifold in most developed countries after World War II in parallel with a series of other immune-mediated diseases. T1D results from gene-environmental interactions. The appearance of disease-associated autoantibodies into the peripheral circulation is the first detectable sign of the initiation of the disease process leading to clinical T1D. The first autoantibodies may appear already before the age of 6 months and the seroconversion rate peaks during the second year of life. This implies that exogenous factors involved in the pathogenesis of T1D must be operative in early life, some of them most likely already during pregnancy. Here, we discuss putative endogenous factors that may contribute to the development of T1D during fetal and early postnatal life. Many environmental factors operative in early life have been implicated in the pathogenesis of T1D, but relatively few have been firmly confirmed.

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Eco-physiological and Antioxidant Responses of Holm Oak ( Quercus ilex L.) Leaves to Cd and Pb

Abstract

Plants of the urban environment are exposed to a wide range of pollutants, including heavy metals. This research studies in situ the eco-physiological and antioxidant responses of holm oak (Q. ilex) leaves to Pb and Cd to assess the mechanisms of metal tolerance in this species, widely used as biomonitor. Leaves of plants grown at parks and roadsides were analyzed for photosynthetic activity, Pb and Cd concentration in tissues and cell-free extracts, thiol groups, D1 and Rubisco protein content, ascorbic acid (AsA) amount, and catalase (CAT) activity. The main results evidenced that Cd concentration was higher in leaves collected at the park out from the downtown; whereas Pb was most abundant in leaves sampled at the roadside nearby the highway. Pb in cell-free extracts was higher in park than in roadside leaves. Although Cd in the leaf tissues was twofold lower than Pb, it was more abundant than Pb in cellular extracts deprived of all particulate matter. Leaves responded to different concentration of Cd and Pb modulating some eco-physiological and biochemical traits, roadside leaves showed reduced leaf lamina, higher content of photosynthetic pigments, hydrogen peroxide, and AsA, as well as higher CAT activity compared to park leaves. In the roadside leaves, a stress condition for photosynthetic apparatus can be hypothesized on the basis of the decline of photochemical activity, the increase of NPQ, and the reduction of Rubisco and D1 protein content. The elevated presence of thiol groups in these leaves suggests a possible role of Pb and Cd in activation of antioxidant responses.

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Sensitization to PR-10 proteins is indicative of distinctive sensitization patterns in adults with a suspected food allergy

The extent of co-sensitization within and between food protein families in an adult population is largely unknown. This study aimed to identify the most frequently recognized components in the PR-10 and storag...

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Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

Abstract

Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients.

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Rhinology Future Debates, an EUFOREA Report.

Rhinology Future Debates, an EUFOREA Report.

Rhinology. 2017 Nov 22;:

Authors: Fokkens WJ, Bachert C, Bernal-Sprekelsen M, Bousquet J, Djandji M, Dorenbaum A, Hakimi-Mehr D, Hendry S, Hopkins C, Leunig A, Mannent L, Mucha D, Onerci M, Pugin B, Toppila-Salmi S, Rowe P, Seys SF, Stimson S, Strzembosz A, Hellings PW

Abstract
The first Rhinology Future Debates was held in Brussels in December 2016, organized by EUFOREA (European Forum for Research and Education in Allergy and Airways diseases). The purpose of these debates is to bring novel developments in the field of Rhinology to the attention of the medical, paramedical and patient community, in a highly credible and balanced context. For the first time in Rhinology, a peer to peer scientific exchange with key experts in the field of rhinology and key medical colleagues from leading industries let to a brainstorming and discussion event on a number of hot issues in Rhinology. Novel developments are presented by key experts from industry and/or key thought leaders in Rhinology, and then followed by a lively debate on the potential positioning of new developments in care pathways, the strengths and weaknesses of the novel development(s), and comparisons with existing and/or competing products, devices, and/or molecules. As all debates are recorded and distributed on-line with limited editing (http://ift.tt/2zvwM6T), EUFOREA aims at maximizing the education of the target groups on novel developments, allowing a critical appraisal of the future and a more rapid implementation of promising novel tools, techniques and/or molecules in clinical practise in Europe. The next Rhinology Future debate will be held in Brussels in December 2017.

PMID: 29166426 [PubMed - as supplied by publisher]

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Anatomy of the sphenopalatine artery and its implications for transnasal neurosurgery.

Anatomy of the sphenopalatine artery and its implications for transnasal neurosurgery.

Rhinology. 2017 Nov 22;:

Authors: Eordogh M, Grimm A, Gawish I, Patonay L, Reisch R, Briner HR, Baksa G

Abstract
BACKGROUND: The knowledge of sinonasal vasculature is inevitable in transnasal neurosurgery. We performed an anatomical study on the sphenopalatine artery from the perspective of skull base procedures.
METHODOLOGY: To analyse the anatomical landmarks of the sphenopalatine artery, arterial skull corrosion casts (26 head halves) underwent endoscopic transnasal phantom surgery. Furthermore, we performed microsurgical dissection on formaldehyde-fixated cadavers with arterial perfusion (14 head halves) as well as studied Cone Beam CT-scans of anonymised patients and cadavers (115 head sides).
RESULTS: In our cadaveric material, the sphenopalatine foramen is located at the transition of the superior and middle nasal meatus (95.0%) or in the superior nasal meatus (5.0%). It is the main entry point of the branches of the sphenopalatine artery into the nasal cavity. In most cadaveric cases (25.0%), at this level there are 2 branches superiorly and 1 vessel inferiorly to the ethmoid crest. An average of 2.4 vessels leave the sphenopalatine foramen superiorly to the ethmoid crest, 97.8% of them belong to the sphenopalatine arterys posterior septal branches. An average of 2.1 branches leave the sphenopalatine foramen inferiorly to the ethmoid crest; all of them belong to the posterior lateral nasal branches. There are no cases with a single artery at the plane of the sphenopalatine foramen. We describe a triangular bony structure bordering the sphenopalatine foramen anteriorly which is built up by the palatine and ethmoid bone as well as the maxilla. According to the radiographic studies, this triangular prominence is surrounded superiorly by a posterior ethmoid cell (57.4%), the sphenoid sinus (41.7%) or the orbit (0.9%) with a varying contribution of the superior nasal meatus; inferolaterally by the maxillary sinus (98.3%) or the pterygopalatine and infratemporal fossa (1.7%) and inferomedially by the middle nasal meatus. The medial vertex of the bony triangle corresponds to the ethmoid crest of the palatine bone. In transnasal endoscopic surgery, the posterior lateral nasal branches of the sphenopalatine artery appear at the triangle´s inferomedial edge, the posterior septal branches emerge at its superior edge.
CONCLUSIONS: The triangular bony structure is a landmark to find and differentiate the posterior lateral nasal and posterior septal branches of the sphenopalatine artery and to identify the sphenoid sinus.

PMID: 29166425 [PubMed - as supplied by publisher]

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The future in Rhinology: from local treatment, to monoclonals and influencing the microbiome.

The future in Rhinology: from local treatment, to monoclonals and influencing the microbiome.

Rhinology. 2017 Nov 22;:

Authors: Fokkens WJ

Abstract
Over the last few decades, rhinology has been one of the most dynamic and progressive areas of ENT. We have not experienced such an intense period of development since the introduction of nasal corticosteroids in the 1970s.

PMID: 29166424 [PubMed - as supplied by publisher]

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Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care.

Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care.

Rhinology. 2017 Nov 22;:

Authors: Frendo M, Hakansson K, Schwer S, Ravn AT, Meteran H, Porsbjerg C, Backer V, von Buchwald C

Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder associated with lower airway disease. However, only few studies of CRSwNP from outside secondary/tertiary care centres have been published. We recently reported an asthma frequency of 44% and 65% in primary and secondary care patients respectively. Therefore, we hypothesise that inflammation of the lower airways could be present in all CRSwNP patients, even without asthma. Here, we assessed the degree of lower and upper airway inflammation using exhaled and nasal nitric oxide (NO) in primary care CRSwNP patients with and without asthma.
METHODS: Fifty-seven patients who met the EPOS criteria for CRSwNP were prospectively recruited from primary care ear, nose and throat clinics. Nasal endoscopy was performed by an ear, nose and throat specialist upon enrolment. Additionally, 30 healthy controls were enrolled. Expiratory and nasal NO measurements and thorough pulmonary evaluation were performed. Pulmonary disease was diagnosed by a respiratory physician.
RESULTS: Fifty-nine percent of CRSwNP patients with asthma showed elevated expiratory NO; the same was seen in 29% of non-asthmatic CRSwNP patients. Compared with controls, a high level of exhaled NO was significantly more prevalent in CRSwNP irrespective of asthma-status. Nasal NO was significantly lower in patients with CRSwNP compared with controls.
CONCLUSION: Subclinical eosinophilic lower airway inflammation is common in CRSwNP in the primary sector, even in the absence of asthma.

PMID: 29166423 [PubMed - as supplied by publisher]

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Rhinology. 2017 Nov 22;: Authors: Stokes P, Rimmer J Abstract...

Rhinology. 2017 Nov 22;:

Authors: Stokes P, Rimmer J

Abstract
BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) remains a difficult disease for the ENT specialist to manage. Affected patients often report recurrent epistaxis as the most debilitating symptom. The pathogenesis of the disease is due to genetic mutations affecting angiogenesis. For this reason, the anti-angiogenic therapy bevacizumab has gained popularity in the local treatment of epistaxis in patients with HHT.
OBJECTIVE: A systematic review of the efficacy of bevacizumab in local treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, severity and impact on quality of life.
METHODS: A systematic search was performed using the PubMed, MEDLINE and EMBASE databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of intranasal bevacizumab treatment of epistaxis in patients with HHT were included for qualitative analysis.
RESULTS: Thirteen studies (four randomised controlled trials, three prospective studies, three retrospective studies, one case series and two case reports) with a total of 357 patients were included. Local administration (either by submucosal injection or topically) did not have a significant impact on epistaxis duration, frequency, severity or quality of life compared to placebo or other local treatments.
CONCLUSIONS: The available evidence suggests that intranasal bevacizumab treatment does not have a significant effect on epistaxis in patients with HHT. There are several limitations that require further investigation to confidently rule out local bevacizumab as an effective therapy in HHT related epistaxis.

PMID: 29166422 [PubMed - as supplied by publisher]

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OV21/PETROC: A randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer

Abstract

Background

The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC).

Patients and Methods

We performed a multicentre, 2 stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (IV) NACT followed by optimal (<1cm) debulking surgery were randomized to one of 3 treatment arms: 1) IV carboplatin/paclitaxel; 2) IP cisplatin plus IV/IP paclitaxel, or 3) IP carboplatin plus IV/IP paclitaxel. The primary endpoint was 9 month progressive disease rate (PD9). Secondary endpoints included progression free survival (PFS), overall survival (OS), toxicity and quality of life (QOL).

Results

Between 2009 and 2015, 275 patients were randomized. IP cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared IV carboplatin/paclitaxel (n = 101) to IP carboplatin, IV/IP paclitaxel (n = 102). The intention to treat PD9 was lower in the IP carboplatin arm compared to the IV carboplatin arm: 24.5% (95% CI 16.2%-32.9%) vs. 38.6% (95% CI 29.1%- 48.1%) p = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57 - 1.17); p = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) p = 0.40. The IP carboplatin based regimen was well tolerated with no reduction in QOL or increase in toxicity compared to IV administration alone.

Conclusion

In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, IP carboplatin based chemotherapy is well tolerated and associated with an improved PD9 compared to IV carboplatin based chemotherapy.clinicaltrials.gov, NCT01622543

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Prevalence and clinical association of gene mutations through Multiplex Mutation Testing in patients with NSCLC: Results from the ETOP Lungscape Project

Abstract

Background

Reported prevalence of driver gene mutations in non-small cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the ETOP Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathological features and patient outcome (relapse-free survival, time-to-relapse, overall survival).

Methods

Clinically-annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is > 1% for most of the ∼150 (13 genes) mutations covered in the multiplex test.

Results

Multiplex testing has been performed in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years).FFPE samples mostly date from 2005-8, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63µg; 38 cases (1.4%) failed QC and were excluded from study. 95.1% of included cases allowed the complete panel of mutations to be tested.Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9% respectively.KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups.EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers.For all the above mutations, there was no difference in outcome between mutated and non-mutated cases.

Conclusion

Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically-annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.

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New antiemetics: facing the current challenge

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Upholding the human right of children in New Zealand experiencing communication difficulties to voice their needs and dreams

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Sampling of Wide Local Excision Specimens in Cutaneous Malignant Melanoma

Background

Wide local excisions (WLE) are frequently undertaken in the management of cutaneous melanoma; however there is considerable variability in their macroscopic sampling. The aim of our study was to establish evidence-based guidelines for the macroscopic handling of these specimens with a subsequent review of the impact on our service.

Methods

The study group of 128 cases with initial biopsy and subsequent WLE in our institution in 2010 were identified by a computer-generated search. From analysis of this group, guidelines for macroscopic sampling were derived with a repeat search performed in 2012.

Results

Residual melanoma was detected only in those cases in which the original specimen had clear margins of ≤1mm or with a pigmented lesion. A 32% increase in case numbers was noted over this period with a reduction of 6.2% in block numbers. Average block numbers per case were reduced by 2.3 (30.7%).

Conclusions

We have shown that for WLE specimens with no evidence of a macroscopic lesion and clear margins on original biopsy, little is to be gained from extensive sampling. In these cases we recommend a maximum of 3 blocks per case. Reduction in sampling based on this evidence would result in saving valuable laboratory resources.

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When populism takes over the delivery of health care: Venezuela

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DNA replication stress and cancer chemotherapy

Abstract

DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss about the underlying mechanism of cancer therapy from the aspect of DRS.

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HOXC13 promotes proliferation of esophageal squamous cell carcinoma via repressing transcription of CASP3

Summary

Esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer, is one of the most common digestive tumors worldwide. In this study, we confirmed that HOXC13, a member of the homeobox HOXC gene family, was significantly upregulated in ESCC and its overexpression was associated with poorer clinical characteristics and worse prognosis. Moreover, knockdown of HOXC13 inhibited proliferation and induced apoptosis of ESCC via upregulating CASP3. Chromatin Immunoprecipitation analysis revealed that HOXC13 repressed transcription of CASP3 via directly targeting the promotor region of CASP3. We also found that miR-503 downregulated HOXC13, by directly targeting its 3′UTR, and inhibited proliferation of ESCC. In conclusion, our study demonstrates that HOXC13, which is directly targeted by miR-503, promotes proliferation and inhibits apoptosis of ESCC via repressing transcription of CASP3.

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Proliferation genes in lung development associated with the prognosis of lung adenocarcinoma but not squamous cell carcinoma

Abstract

There are many similarities between embryonic development and tumorigenesis, and gene expression profiles show that certain correlations exist between the gene signature during development and the clinical phenotypes of different cancers. Our group previously reported the gene expression profiles of human lung development, and the expression of one group of proliferation-related genes (named as PTN1 genes) steadily decreased during lung development. Here, we examined the prognostic value of PTN1 genes in five independent lung adenocarcinoma (ADC) and five lung independent squamous cell carcinoma (SCC) microarray datasets and found that the expression levels of PTN1 genes were associated with survival in lung ADC but not lung SCC. All the lung ADC datasets contained a set of highly correlated genes from PTN1 genes, but the lung SCC datasets had no similar set of genes. We identified 63 unique core genes from the PTN1 genes in the five lung ADC datasets, 17 of these core genes appeared in at least four of the lung ADC datasets, and the 17 corresponding proteins clearly interacted more strongly with each other in lung ADC than in lung SCC. Moreover, 16 of the 17 core genes play major roles in the G2/M phase of the cell cycle. These data indicate that proliferation-related genes in lung development have a significant prognostic value for lung ADC; the synergistic effects of the 17 core genes play an important role in lung ADC prognosis. These genes may have significant clinical implications for the treatment and prognosis of lung ADC.

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PRIMA-1 induces p53-madiated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation

Abstract

TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and induction of massive apoptosis) has recently been reported to restore the function of mutant TP53; however, its antitumor effect and mechanism in ESCC remain unclear. After evaluating the TP53 mutation status of a panel of eleven ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1 administration on cells with different p53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in TP53-related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying PRIMA-1′s function. An ESCC xenograft model was further used to evaluate the therapeutic effect of PRIMA-1 in vivo. PRIMA-1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in ESCC cell lines with TP53 missense mutations, whereas no apoptosis was induced in ESCC with wild type TP53 and TP53 with frameshift and nonsense mutations. Importantly, the knockdown of Noxa cancelled the apoptosis induced by PRIMA treatment in ESCC cell lines with TP53 missense mutations. PRIMA-1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense mutation. PRIMA-1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in ESCC with TP53 missense mutations.

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Using rotated speech to approximate the acoustic mismatch negativity response to speech

Publication date: January 2018
Source:Brain and Language, Volume 176
Author(s): Ellen Marklund, Francisco Lacerda, Iris-Corinna Schwarz
The mismatch negativity (MMN) response is influenced by the magnitude of the acoustic difference between standard and deviant, and the response is typically larger to linguistically relevant changes than to linguistically irrelevant changes. Linguistically relevant changes between standard and deviant typically co-occur with differences between the two acoustic signals. It is therefore not straightforward to determine the contribution of each of those two factors to the MMN response. This study investigated whether spectrally rotated speech can be used to determine the impact of the acoustic difference on the MMN response to a combined linguistic and acoustic change between standard and deviant. Changes between rotated vowels elicited an MMN of comparable amplitude to the one elicited by a within-category vowel change, whereas the between-category vowel change resulted in an MMN amplitude of greater magnitude. A change between rotated vowels resulted in an MMN ampltude more similar to that of a within-vowel change than a complex tone change did. This suggests that the MMN amplitude reflecting the acoustic difference between two speech sounds can be well approximated by the MMN amplitude elicited in response to their rotated counterparts, in turn making it possible to estimate the part of the response specific to the linguistic difference.

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Cover 2: Editorial Board

Publication date: December 2017
Source:Brain and Language, Volume 175

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Cover 4: TOC/Barcode

Publication date: December 2017
Source:Brain and Language, Volume 175

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Specific Immunotherapy in LAR: a randomized, double-blind placebo controlled trial with Phleum pratense subcutaneous allergen immunotherapy

Abstract

Background

Allergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous immunotherapy (Phl-SCIT) in LAR.

Methods

In a randomized double-blind placebo-controlled study, 56 patients with moderate-severe LAR to grass pollen received Phl-SCIT with a depigmented-polymerized pollen vaccine or placebo for the first year, and Phl-SCIT the second one. The blind was maintained throughout the study. Primary outcome was combined symptoms-medication score (CSMS) during grass pollen season (GPS). Secondary clinical outcomes included organ-specific symptoms, medication free days, rhinitis severity, and asthma control. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal allergen provocation test (NAPT), skin testing, serum levels of specific-IgG4 and specific-IgE, and safety were also evaluated.

Results

SCIT had a short-term and sustained effect with significant improvements of all primary and secondary clinical outcomes and RQLQ score. SCIT significantly increased serum sIgG4 levels and allergen tolerance, from the 6^th to 24^th months of treatment. At the end of the study 83% of patients treated with ≥6 months of SCIT tolerated a concentration of Phl over 50 times higher than baseline, and 56% gave a negative NAPT. SCIT was well-tolerated; six mild local reactions occurred, and there were no serious adverse events related to the study medication.

Conclusions

Subcutaneous immunotherapy with depigmented-polymerized allergen extracts is a safe and clinically effective treatment for LAR to Phleum pratense.clinicaltrials. gov identifier: NCT02126111.

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Genetic Variants in the Platelet-Derived Growth Factor Subunit B Gene Associated with Pancreatic Cancer Risk

Abstract

The PDGF signaling pathway plays important roles in development and progression of human cancers. In this study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer risk in European populations by using three published GWAS datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed by using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with pancreatic cancer risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and P = 4.70x10⁻⁵ for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01x10⁻⁵ for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype carriers had a significantly increased risk of pancreatic cancer than those carrying the T-C haplotype (OR = 1.23, 95% CI = 1.12-1.34, P =5.00 × 10⁻⁶). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1-2 NUGs, particularly among 60-70 age group or males, had an increased risk of pancreatic cancer, compared with those without NUG. Further, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (P = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to pancreatic cancer. Further population and functional validations of our findings are warranted. This article is protected by copyright. All rights reserved.

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Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Abstract

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin(IL)-6, IL-10 and TNF-α and the risk of TC.

A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption.

Adiponectin was inversely associated with TC risk among women (OR_T3vs.T1=0.69, 95%CI: 0.49-0.98, P_trend=0.04) but not among men (OR_T3vs.T1=1.36, 95%CI: 0.67-2.76, P_trend=0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (OR_T3vs.T1=1.59, 95%CI: 1.13-2.25, P_trend=0.01) but not in men (OR_T3vs.T1=1.78, 95%CI: 0.80-3.98, P_trend=0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender.

These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight. This article is protected by copyright. All rights reserved.

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Αρχειοθήκη ιστολογίου

Πέμπτη 23 Νοεμβρίου 2017

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