ESNR—the next 50 years

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Identification of inflammatory response patterns in experimental gingivitis studies

We used novel analytical approaches to identify inflammatory response patterns to plaque accumulation in experimental gingivitis studies in humans. Data from two experimental gingivitis studies [Dataset I (n = 40) and Dataset II (n = 42)], which differed in design and recording methods, were used. Both studies comprised a three‐phase program as follows: pre‐induction period (oral hygiene as usual for Dataset I; professional tooth cleaning for Dataset II); induction period (plaque accumulation); and resolution period (oral hygiene as usual). Clinical recordings of plaque and gingival inflammation were made on days 0, 4, 9, and 14 for Dataset I and on days −14, 0, 7, 21, and 35 for Dataset II. Group‐based‐trajectory and growth curve modeling were used for data analysis. In Dataset I, gingival response to plaque accumulation was found to be lagged in time. Different group‐based response patterns for gingival inflammation were not identified. However, in Dataset II, 'fast' and 'slow' gingival inflammation responders were identified. 'Slow' responders had lagged inflammation responses, whereas 'fast' responders seemed to respond immediately to plaque. The findings show that analytical approaches which consider the data structure allow investigation of the dynamics of the relationship between plaque accumulation and gingival inflammation and facilitate the identification of differential patterns of gingival inflammation development.

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Effect of methacrylated chitosan incorporated in experimental composite and adhesive on mechanical properties and biofilm formation

The lifespan of a resin‐based restoration is limited, with the main reason for failure being secondary caries. Biofilm formation at the tooth–material interface is a necessary etiological agent for caries development. Dental materials with antimicrobial properties may reduce formation of biofilm and thus increase the longevity of restorations. This study aimed to investigate the effect of methacrylated chitosan (CH‐MA), incorporated into the polymeric network of an experimental dental composite and adhesive, on biofilm growth of Streptococcus mutans and to assess the mechanical properties of the modified materials. The methacrylation of low‐molecular‐weight chitosan was achieved and biofilm studies confirmed the antibacterial effect of the modified polymer in solution. Methacrylated chitosan was incorporated into an experimental composite and adhesive, and the modified materials reduced the formation of S. mutans biofilm. The incorporation of CH‐MA did not alter the bond strength of the adhesives. However, the amount of CH‐MA in composite that is required to elicit an antibacterial response challenges the mechanical properties of the material. The hardness and flexural strength of the composite decreased with increasing amounts of CH‐MA. However, flexural strength values still met the requirement in the ISO standard.

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A Multimethod Analysis of Pragmatic Skills in Children and Adolescents With Fragile X Syndrome, Autism Spectrum Disorder, and Down Syndrome

Purpose

Pragmatic language skills are often impaired above and beyond general language delays in individuals with neurodevelopmental disabilities. This study used a multimethod approach to language sample analysis to characterize syndrome- and sex-specific profiles across different neurodevelopmental disabilities and to examine the congruency of 2 analysis techniques.

Method

Pragmatic skills of young males and females with fragile X syndrome with autism spectrum disorder (FXS-ASD, n = 61) and without autism spectrum disorder (FXS-O, n = 40), Down syndrome (DS, n = 42), and typical development (TD, n = 37) and males with idiopathic autism spectrum disorder only (ASD-O, n = 29) were compared using variables obtained from a detailed hand-coding system contrasted with similar variables obtained automatically from the language analysis program Systematic Analysis of Language Transcripts (SALT).

Results

Noncontingent language and perseveration were characteristic of the pragmatic profiles of boys and girls with FXS-ASD and boys with ASD-O. Boys with ASD-O also initiated turns less often and were more nonresponsive than other groups, and girls with FXS-ASD were more nonresponsive than their male counterparts. Hand-coding and SALT methods were largely convergent with some exceptions.

Conclusion

Results suggest both similarities and differences in the pragmatic profiles observed across different neurodevelopmental disabilities, including idiopathic and FXS-associated cases of ASD, as well as an important sex difference in FXS-ASD. These findings and congruency between the 2 language sample analysis techniques together have important implications for assessment and intervention efforts.

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Sinus floor elevation in sites with a perforated schneiderian membrane: What is the effect of placing a collagen membrane in a rabbit model?

Abstract

Objective

To investigate the healing following sinus grafting in sites with a perforated schneiderian membrane repaired using a collagen membrane, compared to control sites without membrane perforation.

Materials & Methods

Following elevation of the sinus membrane in 16 rabbits, each sinus was assigned to one of the following groups: (i) intentional schneiderian membrane perforation, followed by the placement of a collagen membrane and bone grafting (group SMP), (ii) bone grafting without a perforation of the schneiderian membrane and without a collagen membrane placement (control group). At 2 and 4 weeks (n=8 for each time‐point), micro‐computed tomographic (micro‐CT) and histomorphometric analyses were performed.

Results

Overall new bone formation in group SMP was significantly delayed compared to the control group at 2 and 4 weeks (1.58±1.25 vs. 9.23±2.69% at 2 weeks, 10.43±3.55 vs. 17.86±4.11% at 4 weeks, p<0.05). At 2 weeks, new bone formation for the areas close to lateral (1.19±2.02%) and medial sinus bone walls (3.17±1.98%) was markedly delayed in group SMP compared to the control group (13.08±6.13 and 12.75±5.63%, respectively, p<0.05), but there was no statistical difference in those areas at 4 weeks (p>0.05). The augmented volumes at 2 and 4 weeks were not statistically significantly different in both groups.

Conclusion

The perforation of the schneiderian membrane and the repair using a collagen membrane delayed new bone formation in the augmented sinuses. However, the extension of the collagen membrane on the sinus bone walls was also attributable to this delayed bone formation.

This article is protected by copyright. All rights reserved.

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Identification of Pen m 4 as a potential cause of occupational asthma to Gammarus shrimp

We present the case of a 34-year-old male patient employed for 8 years in a company manufacturing and packaging animal feed. The patient developed occupational asthma to dry Gammarus powder. The diagnosis was ...

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Prognostic significance of bone morphogenetic protein 6 (BMP6) expression, clinical and pathological factors in clinically node-negative oral squamous cell carcinoma (OSCC)

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome.

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A simple method to estimate the linear length of the orbital floor in complex orbital surgery

The orbital floor (OrF) and infraorbital rim (IOR) repair in cases of complete destruction is challenging mainly due to the fact that the defect length cannot be measured. The aim of the current study is to develop a method of calculating the Orf length by using the gender and the lengths of the medial, superior and lateral orbital walls (OrW) of the same orbit.

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The feasibility of rib grafts in long span mandibular defects reconstruction: a long term follow up

To evaluate the efficiency of reconstruction of long span mandibular defects using split rib bundle bone graft.

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Ultrafast pediatric chest computed tomography: comparison of free-breathing vs. breath-hold imaging with and without anesthesia in young children

Abstract

Background

General anesthesia (GA) or sedation has been used to obtain good-quality motion-free breath-hold chest CT scans in young children; however pulmonary atelectasis is a common and problematic accompaniment that can confound diagnostic utility. Dual-source multidetector CT permits ultrafast high-pitch sub-second examinations, minimizing motion artifact and potentially eliminating the need for a breath-hold.

Objective

The purpose of this study was to evaluate the feasibility of free-breathing ultrafast pediatric chest CT without GA and to compare it with breath-hold and non-breath-hold CT with GA.

Materials and methods

Young (≤3 years old) pediatric outpatients scheduled for chest CT under GA were recruited into the study and scanned using one of three protocols: GA with intubation, lung recruitment and breath-hold; GA without breath-hold; and free-breathing CT without anesthesia. In all three protocols an ultrafast high-pitch CT technique was used. We evaluated CT images for overall image quality, presence of atelectasis and motion artifacts.

Results

We included 101 scans in the study. However the GA non-breath-hold technique was discontinued after 15 scans, when it became clear that atelectasis was a major issue despite diligent attempts to mitigate it. This technique was therefore not included in statistical evaluation (86 remaining patients). Overall image quality was higher (P=0.001) and motion artifacts were fewer (P<.001) for scans using the GA with intubation and recruitment technique compared to scans in the non-GA free-breathing group. However no significant differences were observed regarding the presence of atelectasis between these groups.

Conclusion

We demonstrated that although overall image quality was best and motion artifact least with a GA-breath-hold intubation and recruitment technique, free-breathing ultrafast pediatric chest CT without anesthesia provides sufficient image quality for diagnostic purposes and can be successfully performed both without and with contrast agent in young infants.

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Auditory predictions shape the neural responses to stimulus repetition and sensory change

Publication date: Available online 9 November 2018

Source: NeuroImage

Author(s): Raffaele Cacciaglia, Jordi Costa-Faidella, Katarzyna Zarnowiec, Sabine Grimm, Carles Escera

Abstract

Perception is a highly active process relying on the continuous formulation of predictive inferences using short-term sensory memory templates, which are recursively adjusted based on new input. According to this idea, earlier studies have shown that novel stimuli preceded by a higher number of repetitions yield greater novelty responses, indexed by larger mismatch negativity (MMN). However, it is not clear whether this MMN memory trace effect is driven by more adapted responses to prior stimulation or rather by a heightened processing of the unexpected deviant, and only few studies have so far attempted to characterize the functional neuroanatomy of these effects. Here we implemented a modified version of the auditory frequency oddball paradigm that enables modeling the responses to both repeated standard and deviant stimuli. Fifteen subjects underwent functional magnetic resonance imaging (fMRI) while their attention was diverted from auditory stimulation. We found that deviants with longer stimulus history of standard repetitions yielded a more robust and widespread activation in the bilateral auditory cortex. Standard tones repetition yielded a pattern of response entangling both suppression and enhancement effects depending on the predictability of upcoming stimuli. We also observed that regularity encoding and deviance detection mapped onto spatially segregated cortical subfields. Our data provide a better understanding of the neural representations underlying auditory repetition and deviance detection effects, and further support that perception operates though the principles of Bayesian predictive coding.

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Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance

Publication date: Available online 9 November 2018

Source: NeuroImage

Author(s): Kaitlin Cassady, Holly Gagnon, Poortata Lalwani, Molly Simmonite, Bradley Foerster, Denise Park, Scott J. Peltier, Myria Petrou, Stephan F. Taylor, Daniel H. Weissman, Rachael D. Seidler, Thad A. Polk

Abstract

Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.

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Optimising neonatal fMRI data analysis: Design and validation of an extended dHCP preprocessing pipeline to characterise noxious-evoked brain activity in infants

Publication date: Available online 8 November 2018

Source: NeuroImage

Author(s): Luke Baxter, Sean Fitzgibbon, Fiona Moultrie, Sezgi Goksan, Mark Jenkinson, Stephen Smith, Jesper Andersson, Eugene Duff, Rebeccah Slater

Abstract

The infant brain is unlike the adult brain, with considerable differences in morphological, neurodynamic, and haemodynamic features. As the majority of current MRI analysis tools were designed for use in adults, a primary objective of the Developing Human Connectome Project (dHCP) is to develop optimised methodological pipelines for the analysis of neonatal structural, resting state, and diffusion MRI data. Here, in an independent neonatal dataset we have extended and optimised the dHCP fMRI preprocessing pipeline for the analysis of stimulus-response fMRI data. We describe and validate this extended dHCP fMRI preprocessing pipeline to analyse changes in brain activity evoked following an acute noxious stimulus applied to the infant's foot. We compare the results obtained from this extended dHCP pipeline to results obtained from a typical FSL FEAT-based analysis pipeline, evaluating the pipelines' outputs using a wide range of tests. We demonstrate that a substantial increase in spatial specificity and sensitivity to signal can be attained with a bespoke neonatal preprocessing pipeline through optimised motion and distortion correction, ICA-based denoising, and haemodynamic modelling. The improved sensitivity and specificity, made possible with this extended dHCP pipeline, will be paramount in making further progress in our understanding of the development of sensory processing in the infant brain.

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Allergen‐specific IgE over time in women before, during and after pregnancy

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Quantitative Assessment of Tumor Cell Proliferation in Brain Gliomas with Dynamic Contrast-Enhanced MRI

Publication date: Available online 8 November 2018

Source: Academic Radiology

Author(s): Jia Shen Jiang, Ye Hua, Xue Jun Zhou, Dan Dan Shen, Jin Long Shi, Min Ge, Qi Nan Geng, Zhong Zheng Jia

Rationale and Objectives

This study aimed to investigate whether volume transfer constant (K^trans) and volume of extravascular extracellular space per unit volume of tissue (V_e) derived from dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) could quantitatively assess the tumor proliferation index (Ki-67) of gliomas noninvasively.

Materials and Methods

The preoperative DCE MRI data of 69 patients with pathologically confirmed glioma (28, 8, and 33 cases in grades Ⅱ, Ⅲ, and Ⅳ) were retrospectively reviewed. The maximal K^trans and V_e were measured in the tumor body. The immunohistochemistry was used to detect the expression of Ki-67 proteins in glioma specimens. The Mann–Whitney U test was applied to analyze the differences in K^trans, V_e, and Ki-67 index across histologically defined glioma grades. Spearman correlation was performed between K^trans, V_e, and Ki-67 index. The receiver operating characteristic curve analysis was used to determine the cutoff values of K^trans and V_e in distinguishing different Ki-67 index expression levels.

Results

K^trans, V_e, and Ki-67 index of grade Ⅱ (0.027 min⁻¹, 0.065, 4.04%) were significantly lower than those of grade Ⅲ (0.093 min⁻¹, 0.297, 25.13%) and Ⅳ (0.100 min⁻¹, 0.299, 25.37%). Both K^trans and V_e significantly correlated with the Ki-67 index in all tumors and high-grade gliomas (HGGs, grade Ⅲ and Ⅳ). The receiver operating characteristic curve analysis revealed that the cutoff values for K^trans (0.079 min⁻¹) and V_e (0.249) provided the best combination of sensitivity and specificity to distinguish the gliomas with high Ki-67 index from those with low Ki-67 index.

Conclusion

The DCE MRI-derived parameters were valuable in assessing the tumor cell proliferation in HGG noninvasively.

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Cost-Effectiveness Analysis: An Overview of Key Concepts, Recommendations, Controversies, and Pitfalls

Publication date: Available online 8 November 2018

Source: Academic Radiology

Author(s): Nadja Kadom, Jason N. Itri, Anna Trofimova, Hansel J. Otero, Michal Horný

The field of radiology has witnessed a burst of technological advances that improve diagnostic quality, reduce harm to patients, support clinical needs, and better serve larger more diverse patient populations. One of the critical challenges with these advances is proving that value outweighs the cost. The use of cutting-edge technology is often expensive, and the reality is that our society cannot afford all the screening and diagnostic tests that are being developed. At the societal level, we need tools to help us decide which health programs should be funded. Therefore, decision makers are increasingly looking toward scientific methods to compare health technologies in order to improve allocation of resources. One of such methods is cost-effectiveness analysis. In this article, we review key features of cost-effectiveness analysis and its specific issues as they relate to radiology.

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Role of induction chemotherapy in sinonasal malignancies: a systematic review

Background

Cancers of the paranasal sinuses are rare tumors that tend to be aggressive and usually are diagnosed at an advanced stage. Despite being rare, these tumors include a wide spectrum of histological subtypes with different biological behaviors. Choosing the optimal treatment modalities and analyzing the different oncological outcomes is therefore challenging. This study aims to evaluate the role of induction chemotherapy prior to definitive local therapy for sinonasal malignancies.

Methods

A systematic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines was conducted. With the assistance of a medical librarian, data sources including MEDLINE, PubMed, Cochrane library, EMBASE, NCBI Bookshelf, National Guideline Clearinghouse, and Clinicaltrials.gov were searched using a customized search strategy that yielded 1758 articles. Inclusion criteria used were as follows: (1) the study has a patient population with 3 or more patients with previously untreated sinonasal malignancies; (2) patients underwent induction chemotherapy prior to definitive local therapy; (3) pretreatment staging information was documented; (4) overall survival was reported by histology type either in table or Kaplan‐Meier format. Nine studies with 220 patients ultimately met inclusion criteria and were analyzed in groups based on tumor histology.

Results

For squamous cell carcinoma (SCC), the 5‐year overall survival was 51%. For neuroendocrine tumors, the 5‐year overall survival was 78%. Eighteen percent (18%) of patients with pretreatment orbital involvement ultimately underwent orbital exenteration.

Conclusion

Induction chemotherapy in the management of sinonasal malignancies has similar overall survival outcomes as other standard treatment modalities and can be offered as an option to patients as part of multimodality therapy.

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Inter-observer Variability in the American College of Radiology Thyroid Imaging Reporting and Data System: In-Depth Analysis and Areas for Improvement

Publication date: Available online 8 November 2018

Source: Ultrasound in Medicine & Biology

Author(s): Malak Itani, Richard Assaker, Mariam Moshiri, Theodore J. Dubinsky, Manjiri K. Dighe

Abstract

The American College of Radiology (ACR) introduced a new standardized system for management of thyroid nodules, the Thyroid Imaging Reporting and Data System (TI-RADS). The purpose of this retrospective study is to evaluate the inter-observer variability in applying TI-RADS in clinical practice without prior dedicated training. We evaluated a total of 180 nodules constituting all consecutive thyroid aspirations performed in the radiology department between January 1, 2014 and June 30, 2014, with exclusion of histologically inadequate samples. Four radiologists, blinded to each other's evaluation and to final pathology results, evaluated all of the nodules based on the TI-RADS lexicon. TI-RADS score and management recommendations were then deduced from the inputted features. Statistical analysis was performed to determine inter-observer agreement among all readers, as well as between each two readers, in all TI-RADS sonographic features and for recommended management per TI-RADS score with multi-user Cohen's κ (Light's κ) and percentage agreement using R. There was fair-to-moderate inter-observer agreement in nodule composition (two-reader κ range: 0.327–0.533) and presence of calcifications (κ range: 0.229–0.527), but poor-to-fair agreement in echogenicity (κ range: 0.141–0.355), shape (κ range: 0.0729–0.513) and margins (κ range: 0.176–0.283). There was fair inter-observer agreement regarding management recommendations (κ range: 0.242–0.359).

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Sagittal skeletal correction using symphyseal miniplate anchorage systems

Abstract

Objectives

Aim of this study is to evaluate success rates and complications related with symphyseal miniplate anchorage systems used for treatment of Class 2 and Class 3 deformities.

Methods

A total of 58 miniplates applied to 29 growing patients were evaluated. The first group comprised 24 symphyseal miniplates applied to 12 patients and Forsus Fatigue Resistant Devices were attached to the head of the miniplates for mandibular advancement. The second group consisted of 34 symphyseal miniplates applied to 17 patients and intermaxillary elastics were applied between acrylic appliances placed on the maxillary dental arch and the symphyseal miniplates for maxillary protraction. Success rate and complications of the symphyseal plate–screw anchorage system were evaluated.

Results

The overall success rate of symphseal miniplates was 87.9%. Six miniplates showed severe mobility and 2 miniplates broke during orthodontic treatment. Infection, miniplate mobility and mucosal hypertrophy were statistically different between the two groups.

Conclusions

Symphyseal miniplates were generally used as successful anchorage units in most patients. Infection, mobility, and mucosal hypertrophy occurred more frequently in Class 2 deformity correction. However, the success rates regarding the two treatment modalities were comparable.

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Exploiting social and local contexts propagation for inducing Chinese microblog-specific sentiment lexicons

Publication date: Available online 8 November 2018

Source: Computer Speech & Language

Author(s): Chuanjun Zhao, Suge Wang, Deyu Li

Abstract

Sentiment lexicons including opinion words, sentiment phrases, and idioms with sentiment polarities play an important role in sentiment analysis tasks. Apart from explicit sentiment features, extracting implicit sentiment features is a challenging research issue. The sentiment expression is very domain-specific, and constructing a general sentiment lexicon that is suitable for all domains is hard or even impossible. In this paper, we propose a novel sentiment unit context propagation framework to extract Chinese microblog-specific explicit and implicit sentiment features. In the process of the selection of seed sentiment units, we select the seed sentiment units that have a large standard degree of centrality with other units, and mark these units with sentiment labels using general sentiment lexicons and manual calibrations. To realize sentiment label propagation from a small amount of labeled sentiment units to unlabeled ones, we exploit local contexts, topic features, and social relationships among users in microblog social networks. After that, the sentiment scores of units are calculated using unit context sentiment propagation. Experiments on two real-world microblog data sets demonstrate that our method can generate microblog-specific sentiment lexicons effectively. Furthermore, the sentiment classification accuracies significantly outperform state-of-the-art baselines.

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Estimating Post-Editing Time Using a Gold-Standard Set of Machine Translation Errors

Publication date: Available online 8 November 2018

Source: Computer Speech & Language

Author(s): Arda Tezcan, Véronique Hoste, Lieve Macken

Abstract

With the improved quality of Machine Translation (MT) systems in the last decades, post-editing (the correction of MT errors) has gained importance in Computer-Assisted Translation (CAT) workflows. Depending on the number and the severity of the errors in the MT output, the effort required to post-edit varies from sentence to sentence. The existing Quality Estimation (QE) systems provide quality scores that reflect the quality of an MT output at sentence level or word level. However, they fail to explain the relationship between different types of MT errors and the required post-editing effort to correct them. We suggest a more informative approach to QE in which different types of MT errors are detected in a first step, which are then used to estimate post-editing effort in a second step. In this paper we define the upper boundary of such a system. We use different machine learning methods to estimate Post-Editing Time (PET) by using a gold-standard set of MT errors as features. We show that post-editing time can be estimated with high accuracy when all the translation errors in the MT output are known. Furthermore, we apply feature selection methods and investigate the predictive power of different MT error types on PET. Our results show that the same prediction performance can be achieved by only using a small subset of MT error types, indicating that successful two-step QE systems can be built with less effort in the future, by detecting only the error types with highest predictive power.

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Characterization of the thymus in Lrp4 myasthenia gravis: Four cases

Publication date: Available online 8 November 2018

Source: Autoimmunity Reviews

Author(s): Inga Koneczny, Dorit Rennspiess, Florit Marcuse, Myurgia Abdul Hamid, Marina Damas, Jos Maessen, Paul Van Schil, Abhishek Saxena, Paraskevi Zisimopoulou, Konstantinos Lazaridis, Mark Woodhall, Katerina Karagiorgou, John Tzartos, Socrates Tzartos, Marc H. De Baets, Peter C. Molenaar, Alexander Marx, Axel zur Hausen, Mario Losen, Pilar Martinez-Martinez

Abstract

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen. In early-onset AChR MG (EOMG), the thymus plays an important role in immunopathogenesis, and early thymectomy is beneficial. It is still unknown if the thymus plays any role in Lrp4-MG. In this pilot study, we compared thymus samples from four patients with Lrp4-MG (one pre-treated with immunosuppressive drugs), four non-MG controls and five EOMG patients (not pretreated with immunosuppressive drugs). Immunohistochemistry of the Lrp4-MG thymi revealed normal architecture, with normal numbers and distribution of B-cells, lymphoid follicles and Hassall's corpuscles. Primary CD23⁺ lymphoid follicles were similarly infrequent in Lrp4-MG and control thymic sections. In none of the control or Lrp4-MG thymi did we find secondary follicles with CD10⁺ germinal centers. These were evident in 2 of the 5 EOMG thymi, where primary lymphoid follicles were also more frequent on average, thus showing considerable heterogeneity between patients. Even if characteristic pathological thymic changes were not observed in the Lrp4 subgroup, we cannot exclude a role for the thymus in Lrp4-MG pathogenesis, since one Lrp4-MG patient went into clinical remission after thymectomy alone (at one year follow-up) and two more improved after thymectomy in combination with immunosuppressive therapy.

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New delivery forms of nasal corticosteroids

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Wytske Fokkens, Sietze Reitsma

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Eosinophil progenitor levels correlate with tissue pathology in pediatric eosinophilic esophagitis

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Justin T. Schwartz, David W. Morris, Margaret H. Collins, Marc E. Rothenberg, Patricia C. Fulkerson

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Engineering of structural variants of the major peanut allergens Ara h 2 and Ara h 6 for allergen-specific immunotherapy

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Merima Bublin, Maria Kostadinova, Christian Radauer, Eva-Maria Varga, Christine Hafner, Klara Schmidthaler, Aziza Saidova, Soheila J. Maleki, Zsolt Szépfalusi, Thomas Eiwegger, Heimo Breiteneder

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Efficacy and safety of histamine H4 receptor antagonist ZPL-3893787 in atopic dermatitis

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Thomas Werfel, Gary Layton, Michael Yeadon, Lyndsey Whitlock, Ian Osterloh, Pablo Jimenez, Wai Liu, Victoria Lynch, Aliya Asher, Athanasios Tsianakas, Lynn Purkins

Abstract

Background

Histamine 4 (H₄) receptor antagonists are potential novel treatments for inflammatory skin diseases including atopic dermatitis (AD).

Objective

To study the efficacy and safety of ZPL-3893787 (selective H₄ receptor antagonist) in moderate/severe AD.

Methods

A randomised, double-blind, placebo-controlled, parallel-group study was conducted to evaluate ZPL-3893787 (30mg) once daily oral therapy in adult patients with moderate/severe AD. Patients were randomized (2:1), to ZPL-3893787 (n=65) or placebo (n=33) for 8 weeks. Patients had a history of AD for >12 months, Eczema Area and Severity Index (EASI) of ≥12 and ≤48, Investigator's Global Assessment (IGA) ≥3, pruritus score of ≥5 (0-10 scale) and AD of ≥10% body surface area (BSA). Efficacy parameters included EASI, IGA, SCORing Atopic Dermatitis (SCORAD), and pruritus assessment.

Results

Treatment with oral ZPL-3893787 showed a 50% reduction in EASI score compared to 27% for placebo. The placebo-adjusted reduction in EASI score at Week 8 was 5.1; 1-sided p=0.01. Clear or almost-clear IGA scores were 18.5% with ZPL-3893787 vs placebo 9.1%. SCORAD exhibited 41% reduction with ZPL-3893787 vs 26% placebo (placebo-adjusted reduction of 10.0; p=0.004). There was a 3-point reduction (scale 1-10) in pruritus with ZPL-389, but there was a similar reduction with placebo, resulting in a non-significant difference (p=0.249). Patient reported pruritus subscore obtained from SCORAD was reduced with ZPL-3893787 compared to placebo at Week 8 (non-significant). ZPL-3893787 was well tolerated.

Conclusion

These results showed for the first time that ZPL-3893787 improved inflammatory skin lesions in patients with AD, confirming H4 receptor antagonism as a novel therapeutic option.

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Peak Flow Variability In Childhood And Body Mass Index In Adult Life

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Enrico Lombardi, Debra A. Stern, Duane Sherrill, Wayne J. Morgan, Anne L. Wright, Judith Garcia-Aymerich, Ignasi Serra Pons, Stefano Guerra, Fernando D. Martinez

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Novel locus for atopic dermatitis in African Americans and replication in European Americans

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Berta Almoguera, Lyam Vazquez, Frank Mentch, Michael E. March, John J. Connolly, Peggy L. Peissig, James G. Linneman, María del Carmen Plaza-Serón, Maria Pino-Yanes, Esteban G. Burchard, Murray Brilliant, Patrick Sleiman, Hakon Hakonarson

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Identification of inhibitory mechanisms in pseudo-allergy involving Mrgprb2/MRGPRX2-mediated mast cell activation

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Ayako Takamori, Kumi Izawa, Ayako Kaitani, Tomoaki Ando, Yoko Okamoto, Akie Maehara, Atsushi Tanabe, Masakazu Nagamine, Hiromichi Yamada, Shino Uchida, Koichiro Uchida, Masamichi Isobe, Tomoki Hatayama, Daiki Watanabe, Taiki Ando, Takuma Ide, Moe Matsuzawa, Keiko Maeda, Nobuhiro Nakano, Naoto Tamura

Ceramide-CD300f binding inhibits mouse Mrgprb2 (human MrgprX2)-mediated mast cell activation, thereby suppressing pseudo-allergic reactions. CD300f could be a therapeutic target against IgE-independent pseudo-allergy as well as IgE-dependent allergy.

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Innate immune crosstalk in asthmatic airways: innate lymphoid cells coordinate the polarization of lung macrophage

Publication date: Available online 9 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Jihyun Kim, Yuna Chang, Boram Bae, Kyoung-Hee Sohn, Sang-Heon Cho, Doo Hyun Chung, Hye Ryun Kang, Hye Young Kim

Abstract

Background

Recent studies have emphasized the role of innate lymphoid cells (ILCs) in the development of asthma. The involvement of group 2 ILCs (ILC2s) in asthma is well studied, however, the participation of other types of ILCs in the development of asthma remains unclear.

Objective

This study aims to understand the role of various ILCs in the patients with asthma, especially their effect on the polarization of macrophages.

Methods

Each subset of ILCs and macrophages in induced sputum from 51 steroid-naïve asthma patients and 18 healthy donors analyzed by flow cytometry. To determine whether the polarization of macrophages could be regulated by ILCs, alveolar macrophages (AM) were sorted; and co-cultured with each subset of ILCs.

Results

In addition to ILC2s, ILC1s and ILC3s were increased in the induced sputum from asthmatics when compared with the healthy controls. The dominance of macrophages in induced sputum was more prominent in asthmatics than healthy controls. A positive correlation between ILC2s and M2 macrophages and that of ILC1s/ILC3s and M1 macrophages observed. Co-culture of ILC2s with AMs induced the expression of M2 macrophage-related genes, whereas co-culture of ILC1s and ILC3s with AMs induced the expression of M1 macrophage-related genes via cytokine secretion as well as cell-cell contact.

According to the inflammatory signature, patients with eosinophilic asthma have more ILC2s and M2 macrophages while those with non-eosinophilic asthma present are M1 macrophages dominant profile.

Conclusion

A different subset of ILCs regulates the polarization of macrophages, contributing to developing the distinct phenotype of asthma.

Graphical abstract

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