FDG PET versus CT radiomics to predict outcome in malignant pleural mesothelioma patients.

BACKGROUND: Careful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics-a quantitative method for image analysis-has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated. MATERIALS AND METHODS: This study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS. RESULTS: For the PFS a concordance index (c-index) of 0.67 (95% CI 0.52-0.82) and 0.66 (95% CI 0.57-0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS. CONCLUSION: We were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.

Reproducibility assessment of Delaire cephalometric analysis using reconstructions from computed tomography.

INTRODUCTION: Cephalometry performed on sagittal teleradiographic X-rays is commonly used for the planification of orthognathic procedures. Tomographic imaging techniques (computer tomography or cone-beam computer tomography) are more and more prescribed for the assessment of complex occlusofacial anomalies. In this study, we intended to evaluate if teleradiographic X-rays reconstructed from computer tomography (CT) can be used to trace reliable cephalometric analyses. We assessed the inter- and intra-observer reproducibility of a simplified Delaire analysis (Top 12), one of the numerous common cephalometric analyses, performed with the Delaire Evolution software on three sets of X-rays: (1) conventional cephalometric X-rays, (2) 2D reconstructions obtained from the CT scans of the same patients and (3) 2D reconstructions obtained from CT scans of dry skulls without a cervical spine (anthropological material). Our primary goal was to assess X-rays reconstructed from tomographies as an alternative for conventional cephalometric X-rays. Our secondary goal was to assess whether computerized cephalometric analysis was a reproducible technique, both on clinical and anthropological material. MATERIALS AND METHODS: We included 10 consecutive adult patients admitted for orthodontic assessment who had benefited from both lateral cephalometric X-rays and from CT-scans. We also included 10 CT-scans from adult dry skulls without a cervical spine, from the collections of the Muséum National d'Histoire Naturelle (Musée de l'Homme, Paris, France). Cephalometric X-rays were reconstructed from CT-scans of both patients and dry skulls using Carestream® (Carestream Health inc., New York, USA). Simplified Delaire analyses (Top12) were conducted by 2 observers using the Delaire Evolution software (JDel, Nantes, France), on the 3 sets of cephalometric X-rays: (1) 10 standard cephalometric X-rays from the orthodontic patients, (2) 10 reconstructed cephalometric X-rays from the CT scans of the orthodontic patients and (3) 10 reconstructed cephalometric X-rays from the CT scans of the dry skulls. A standard statistical assessment of reproducibility was conducted using correlation coefficients. RESULTS: We found good inter- and intra-observer reproducibility for standard cephalometric X-rays and reconstructed cephalometric X-rays (Intraclass Correlation Coeficient > 0.75). We did not find any difference for angle measures between the standard cephalometric X-rays and the reconstructed cephalometric X-rays for the group of orthodontic patients (P > 0.05). Delaire cephalometric analysis was not reproducible for cephalometric X-rays without a cervical spine, that is for cephalometric X-rays reconstructed from the CT-scans of dry skulls. DISCUSSION: Delaire computerized simplified Top12 analysis was reproducible for lateral cephalometric X-rays and for reconstructions obtained from CT scans with similar angle measures for a given patient. This analysis does not seem to be reliable for dry skulls without upper cervical spine. This study uses the example of one particular computerized cephalometric analysis in order to show that cephalometric analyses can be performed on lateral reconstructed cephalometric X-rays obtained from CT scans.

Zygomatic bone shape in intentional cranial deformations: a model for the study of the interactions between skull growth and facial morphology.

Intentional cranial deformations (ICD) were obtained by exerting external mechanical constraints on the skull vault during the first years of life to permanently modify head shape. The repercussions of ICD on the face are not well described in the midfacial region. Here we assessed the shape of the zygomatic bone in different types of ICDs. We considered 14 non-deformed skulls, 19 skulls with antero-posterior deformation, nine skulls with circumferential deformation and seven skulls with Toulouse deformation. The shape of the zygomatic bone was assessed using a statistical shape model after mesh registration. Euclidian distances between mean models and Mahalanobis distances after canonical variate analysis were computed. Classification accuracy was computed using a cross-validation approach. Different ICDs cause specific zygomatic shape modifications corresponding to different degrees of retrusion but the shape of the zygomatic bone alone is not a sufficient parameter for classifying populations into ICD groups defined by deformation types. We illustrate the fact that external mechanical constraints on the skull vault influence midfacial growth. ICDs are a model for the study of the influence of epigenetic factors on craniofacial growth and can help to understand the facial effects of congenital skull malformations such as single or multi-suture synostoses, or of external orthopedic devices such as helmets used to correct deformational plagiocephaly.

[Consideration of guidelines, recommendations and quality indicators for treatment of stroke in the dataset "Emergency Department" of DIVI]. / Berücksichtigung von Leitlinien, Empfehlungen und Qualitätsindikatoren zur Schlaganfalltherapie im Datensatz Notaufnahme der DIVI.

BACKGROUND: The dataset "Emergency Department" of the German Interdisciplinary Association of Critical Care and Emergency Medicine (DIVI) has been developed during several expert meetings. Its goal is an all-encompassing documentation of the early clinical treatment of patients in emergency departments. Using the example of the index disease acute ischemic stroke (stroke), the aim was to analyze how far this approach has been fulfilled. MATERIAL AND METHODS: In this study German, European and US American guidelines were used to analyze the extent of coverage of the datasets on current emergency department guidelines and recommendations from professional societies. In addition, it was examined whether the dataset includes recommended quality indicators (QI) for quality management (QM) and in a third step it was examined to what extent national provisions for billing are included. In each case a differentiation was made whether the respective rationale was primary, i.e. directly apparent or whether it was merely secondarily depicted by expertise. In the evaluation an additional differentiation was made between the level of recommendations and further quality relevant criteria. RESULTS: The modular design of the emergency department dataset comprising 676 data fields is briefly described. A total of 401 individual fields, divided into basic documentation, monitoring and specific neurological documentation of the treatment of stroke patients were considered. For 247 data fields a rationale was found. Partially overlapping, 78.9 % of 214 medical recommendations in 3 guidelines and 85.8 % of the 106 identified quality indicators were primarily covered. Of the 67 requirements for billing of performance of services, 55.5 % are primarily part of the emergency department dataset. Through appropriate expertise and documentation by a board certified neurologist, the results can be improved to almost 100 %. CONCLUSION: The index disease stroke illustrates that the emergency department dataset of the DIVI covers medical guidelines, especially 100 % of the German guidelines with a grade of recommendation. All necessary information to document the specialized stroke treatment procedure in the German diagnosis-related groups (DRG) system is also covered. The dataset is also suitable as a documentation tool of quality management, for example, to participate in the registry of the German Stroke Society (ADSR). Best results are obtained if the dataset is applied by a physician specialized in the treatment of patients with stroke (e.g. board certified neurologist). Finally the results show that changes in medical guidelines and recommendations for quality management as well as billing-relevant content should be implemented in the development of datasets for documentation to avoid duplicate documentation.

Pododermatitis in Captive and Free-Ranging Greater Flamingos (Phoenicopterus roseus).

Pododermatitis is frequent in captive flamingos worldwide, but little is known about the associated histopathologic lesions. Involvement of a papillomavirus or herpesvirus has been suspected. Histopathologic evaluation and viral assessment of biopsies from 19 live and 10 dead captive greater flamingos were performed. Selected samples were further examined by transmission electron microscopy and immunohistochemistry. Feet from 10 dead free-ranging greater flamingos were also evaluated. The histologic appearance of lesions of flamingos of increasing age was interpreted as the progression of pododermatitis. Mild histologic lesions were seen in a 3-week-old flamingo chick with no macroscopic lesions, and these were characterized by Micrococcus-like bacteria in the stratum corneum associated with exocytosis of heterophils. The inflammation associated with these bacteria may lead to further histologic changes: irregular columnar proliferations, papillary squirting, and dyskeratosis. In more chronic lesions, hydropic degeneration of keratinocytes, epidermal hyperplasia, and dyskeratosis were seen at the epidermis, as well as proliferation of new blood vessels and increased intercellular matrix in the dermis. Papillomavirus DNA was not identified in any of the samples, while herpesvirus DNA was seen only in a few cases; therefore, these viruses were not thought to be the cause of the lesions. Poor skin health through suboptimal husbandry may weaken the epidermal barrier and predispose the skin to invasion of Micrococcus-like bacteria. Histologic lesions were identified in very young flamingos with no macroscopic lesions; this is likely to be an early stage lesion that may progress to macroscopic lesions.

Shape and volume of craniofacial cavities in intentional skull deformations.

Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.

Reduced nuclear translocation of nuclear factor (NF)-kappaB p65 in the footpad epidermis of dogs infected with distemper virus.

Infection of canine footpads with the canine distemper virus (CDV) can cause massive epidermal thickening (hard pad disease), as a consequence of increased proliferation of keratinocytes and hyperkeratosis. Keratinocytes of canine footpad epidermis containing detectable CDV nucleoprotein antigen and CDV mRNA were shown previously to have increased proliferation indices. Because various proteins that play a role in the proliferation of epidermal cells are viral targets, the potential participation of such proteins in CDV-associated keratinocyte proliferation was investigated. Transforming growth factor-alpha (TGF-alpha), cell cycle regulatory proteins p21, p27 and p53, and nuclear factor (NF)-kappaB transcription factor components p50 and p65 were studied in the footpad epidermis from the following groups of dogs inoculated with CDV: group 1, consisting of seven dogs with clinical distemper and CDV in the footpad epidermis; group 2, consisting of four dogs with clinical distemper but no CDV in the footpad epidermis; group 3, consisting of eight dogs with neither clinical distemper nor CDV in the footpad epithelium. Group 4 consisted of two uninoculated control dogs. The expression of TGF-alpha, p21, p27 and p53, and p50 in the basal layer, lower and upper spinous layers, and in the granular layer did not differ statistically between CDV-positive (group 1) and CDV-negative (groups 2-4) footpad epidermis. However, there were differences in the levels of nuclear and cytoplasmic p65 expression between group 1 dogs and the other three groups. Thus, footpads from group 1 dogs had more keratinocytes containing p65 in the cytoplasm and, conversely, fewer nuclei that were positive for p65. These findings indicate that p65 translocation into the nucleus is reduced in CDV-infected footpad epidermis. Such decreased translocation of p65 may help to explain increased keratinocyte proliferation in hard pad disease and suggests interference of CDV with the NF-kappaB pathway.