The importance of CXCR4 expression in tumor stroma as a potential biomarker in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. METHODS: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. RESULTS: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. CONCLUSIONS: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.

Comparison of deep learning models for digital H&E staining from unpaired label-free multispectral microscopy images.

BACKGROUND AND OBJECTIVE: This paper presents the quantitative comparison of three generative models of digital staining, also known as virtual staining, in H&E modality (i.e., Hematoxylin and Eosin) that are applied to 5 types of breast tissue. Moreover, a qualitative evaluation of the results achieved with the best model was carried out. This process is based on images of samples without staining captured by a multispectral microscope with previous dimensional reduction to three channels in the RGB range. METHODS: The models compared are based on conditional GAN (pix2pix) which uses images aligned with/without staining, and two models that do not require image alignment, Cycle GAN (cycleGAN) and contrastive learning-based model (CUT). These models are compared based on the structural similarity and chromatic discrepancy between samples with chemical staining and their corresponding ones with digital staining. The correspondence between images is achieved after the chemical staining images are subjected to digital unstaining by means of a model obtained to guarantee the cyclic consistency of the generative models. RESULTS: The comparison of the three models corroborates the visual evaluation of the results showing the superiority of cycleGAN both for its larger structural similarity with respect to chemical staining (mean value of SSIM ∼ 0.95) and lower chromatic discrepancy (10%). To this end, quantization and calculation of EMD (Earth Mover's Distance) between clusters is used. In addition, quality evaluation through subjective psychophysical tests with three experts was carried out to evaluate quality of the results with the best model (cycleGAN). CONCLUSIONS: The results can be satisfactorily evaluated by metrics that use as reference image a chemically stained sample and the digital staining images of the reference sample with prior digital unstaining. These metrics demonstrate that generative staining models that guarantee cyclic consistency provide the closest results to chemical H&E staining that also is consistent with the result of qualitative evaluation by experts.

Enfermedad antimembrana basal glomerular en hermanos no gemelos con HLA idéntico / Anti-glomerular basement membrane disease in HLA-identical non-twin siblings

La enfermedad antimembrana basal glomerular (EMBG) es un trastorno autoinmune caracterizado por la presencia de anticuerpos antimembrana basal glomerular (AMBG), hemorragia pulmonar, glomerulonefritis necrotizante y depósito lineal de inmunoglobulinas en inmunofluorescencia directa. La predisposición genética, entre otros factores, posee un papel importante en el desarrollo de la enfermedad. Estudios previos han demostrado que el antígeno leucocitario humano (HLA), HLA-DR15 y HLA- DR4, se asocian con mayor riesgo de presentarla, mientras que el HLA-DR1 y HLA-DR7 han demostrado ser factor de protección frente a su desarrollo.Describimos el primer caso de dos hermanos no gemelos con EMBG con tipaje HLA idéntico, con factor de riesgo HLA-DR4 y factor de protección HLA-DR7. Planteamos la importancia de analizar el tipaje de histocompatibilidad en hermanos de pacientes con EMBG, para determinar el grado de susceptibilidad genética y plantear en ellos un seguimiento estrecho, con el objetivo de lograr un diagnóstico y tratamiento precoces en caso de presentar la enfermedad. (AU)

Anti-glomerular basement membrane disease (AGBM) is an autoinmune disorder characterized by the presence of anti-glomerular basement membrane (anti-GBM) antibodies, alveolar hemorrhage, necrotizing glomerulonephritis, and linear deposition of immunoglobulins through direct inmunofluorescence. Genetic predisposition, among other factors, plays an important role in the development of the disease. Previous studies have shown that HLA-DR15 and HLA-DR4 increase the risk of presenting it, while HLA-DR1 and HLA-DR7 protect against its development.We describe the first case of two non-twin siblings with AGBM and identical HLA, with HLA-DR4 as risk factor and HLA-DR7 as protection factor. We propose the importance of analyzing HLA in siblings of patients with AGBM, to determine the degree of genetic susceptibility and to carry out a close follow-up on them, with the aim of achieving an early diagnosis and treatment in case of presenting the disease. (AU)

Anti-glomerular basement membrane disease in HLA-identical non-twin siblings.

Anti glomerular basement membrane disease (AGBM) is an autoinmune disorder characterised by the presence of anti-glomerular basement membrane (Anti-GBM) antibodies, alveolar hemorrhage, necrotizing glomerulonephritis, and linear deposition of immunoglobulins through direct inmunofluorescence. Genetic predisposition, among other factors, plays an important role in the development of the disease. Previous studies have shown that HLA-DR15 and HLA-DR4 increase the risk of presenting it, while HLA-DR1 and HLA-DR7 protect against its development. We describe the first case of two non-twin siblings with AGBM and identical HLA, with HLA-DR4 as risk factor and HLA-DR7 as protection factor. We propose the importance of analysing HLA in siblings of patients with AGBM, to determine the degree of genetic susceptibility and to carry out a close follow-up on them, with the aim of achieving an early diagnosis and treatment in case of presenting the disease.

Characterization of Permeability Barrier Dysfunction in a Murine Model of Cutaneous Field Cancerization Following Chronic UV-B Irradiation: Implications for the Pathogenesis of Skin Cancer.

Chronic ultraviolet B (UV-B) irradiation is known to be one of the most important hazards acting on the skin and poses a risk of developing photoaging, skin with cutaneous field cancerization (CFC), actinic keratosis (AKs), and squamous cell carcinomas (SCCs). Most of the UV-B light is absorbed in the epidermis, affecting the outermost cell layers, the stratum corneum, and the stratum granulosum, which protects against this radiation and tries to maintain the permeability barrier. In the present work, we show an impairment in the transepidermal water loss, stratum corneum hydration, and surface pH after chronic UV-B light exposure in an immunologically intact mouse model (SKH1 aged mice) of skin with CFC. Macroscopic lesions of AKs and SCCs may develop synchronically or over time on the same cutaneous surface due to both the presence of subclinical AKs and in situ SCC, but also the accumulation of different mutations in keratinocytes. Focusing on skin with CFC, yet without the pathological criteria of AKs or SCC, the presence of p53 immunopositive patches (PIPs) within the epidermis is associated with these UV-B-induced mutations. Reactive epidermis to chronic UV-B exposure correlated with a marked hyperkeratotic hyperplasia, hypergranulosis, and induction of keratinocyte hyperproliferation, while expressing an upregulation of filaggrin, loricrin, and involucrin immunostaining. However, incidental AKs and in situ SCC might show neither hypergranulosis nor upregulation of differentiation markers in the upper epidermis. Despite the overexpression of filaggrin, loricrin, involucrin, lipid enzymes, and ATP-binding cassette subfamily A member 12 (ABCA12) after chronic UV-B irradiation, the permeability barrier, stratum corneum hydration, and surface pH were severely compromised in the skin with CFC. We interpret these results as an attempt to restore the permeability barrier homeostasis by the reactive epidermis, which fails due to ultrastructural losses in stratum corneum integrity, higher pH on skin surface, abundant mast cells in the dermis, and the common presence of incidental AKs and in situ SCC. As far as we know, this is the first time that the permeability barrier has been studied in the skin with CFC in a murine model of SCC induced after chronic UV-B irradiation at high doses. The impairment in the permeability barrier and the consequent keratinocyte hyperproliferation in the skin of CFC might play a role in the physiopathology of AKs and SCCs.

Anti-glomerular basement membrane disease in HLA-identical non-twin siblings. / Enfermedad antimembrana basal glomerular en hermanos no gemelos con HLA idéntico.

Anti-glomerular basement membrane disease (AGBM) is an autoinmune disorder characterized by the presence of anti-glomerular basement membrane (anti-GBM) antibodies, alveolar hemorrhage, necrotizing glomerulonephritis, and linear deposition of immunoglobulins through direct inmunofluorescence. Genetic predisposition, among other factors, plays an important role in the development of the disease. Previous studies have shown that HLA-DR15 and HLA-DR4 increase the risk of presenting it, while HLA-DR1 and HLA-DR7 protect against its development. We describe the first case of two non-twin siblings with AGBM and identical HLA, with HLA-DR4 as risk factor and HLA-DR7 as protection factor. We propose the importance of analyzing HLA in siblings of patients with AGBM, to determine the degree of genetic susceptibility and to carry out a close follow-up on them, with the aim of achieving an early diagnosis and treatment in case of presenting the disease.

Metastatic Melanoma Negative for 5 Melanocytic Markers, Complete Regressed Primary Cutaneous Melanoma, and Melanoma-Associated Leukoderma in the Same Patient.

Melanomas with complete histological regression have been seen very infrequently. On the other hand, the diagnosis of metastatic melanoma is based on the histopathology and positivity of markers such as S100, Melan-A, and HMB-45 whose sensitivity is 99%, 82%, and 76%, respectively. It is very rare that metastatic melanomas and even more primary melanoma are negative for all of these markers. In these rare cases, there is usually a known primary. We present the case of a 82-year-old woman with a erythematous mass in the left groin and a 1-cm black-bluish irregular nodule on the skin of the ipsilateral foot. This lesion was clinical and dermoscopically compatible with primary melanoma. In the histological evaluation of the skin, a dermis full of melanophages and hemosiderophages were found in a background of fibrosis, scarce lymphocytic infiltrate, and neovascularization. Any cells expressing melanocytic markers were observed. It was diagnosed as tumoral melanosis. Lymph nodes showed a proliferation of atypical epithelioid cells with eosinophilic cytoplasm. Mitosis was conspicuous. Tumoral cells were vimentin and CD99 positive, and S100, CD34, HMB-45, Melan-A, SOX 10, tyrosinase, C-KIT, CD45, and CKAE1/AE3 negative, and BRAF-V600 mutated was detected. During follow-up, atypical vitiligo-like lesions were discovered, suggesting the diagnosis of metastatic melanoma totally regressed in our patient.

The human olfactory system in two proteinopathies: Alzheimer's and Parkinson's diseases.

Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-ß peptide and neurofibrillary tangles of tau protein in Alzheimer's disease, and Lewy bodies mostly composed of α-synuclein in Parkinson's disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal-hippocampal-cortical and amygdala-dorsal motor vagal nucleus) of network dysfunction in Alzheimer's and Parkinson's diseases.

Data for glomeruli characterization in histopathological images.

The data presented in this article is part of the whole slide imaging (WSI) datasets generated in European project AIDPATH This data is also related to the research paper entitle "Glomerulosclerosis Identification in Whole Slide Images using Semantic Segmentation", published in Computer Methods and Programs in Biomedicine Journal [1]. In that article, different methods based on deep learning for glomeruli segmentation and their classification into normal and sclerotic glomerulous are presented and discussed. The raw data used is described and provided here. In addition, the detected glomeruli are also provided as individual image files. These data will encourage research on artificial intelligence (AI) methods, create and compare fresh algorithms, and measure their usability in quantitative nephropathology.

Glomerulosclerosis identification in whole slide images using semantic segmentation.

BACKGROUND AND OBJECTIVE: Glomeruli identification, i.e., detection and characterization, is a key procedure in many nephropathology studies. In this paper, semantic segmentation based on convolutional neural networks (CNN) is proposed to detect glomeruli using Whole Slide Imaging (WSI) follows by a classification CNN to divide the glomeruli into normal and sclerosed. METHODS: Comparison between U-Net and SegNet CNNs is performed for pixel-level segmentation considering both a two and three class problem, that is, a) non-glomerular and glomerular structures and b) non-glomerular normal glomerular and sclerotic structures. The two class semantic segmentation result is then used for a CNN classification where glomerular regions are divided into normal and global sclerosed glomeruli. RESULTS: These methods were tested on a dataset composed of 47 WSIs belonging to human kidney sections stained with Periodic Acid Schiff (PAS). The best approach was the SegNet for two class segmentation follows by a fine-tuned AlexNet network to characterize the glomeruli. 98.16% of accuracy was obtained with this process of consecutive CNNs (SegNet-AlexNet) for segmentation and classification. CONCLUSION: The results obtained demonstrate that the sequential CNN segmentation-classification strategy achieves higher accuracy reducing misclassified cases and therefore being the methodology proposed for glomerulosclerosis detection.

Short and long-term outcomes of underwater EMR compared to the traditional procedure in the real clinical practice

Background and aims: underwater endoscopic mucosal resection (U-EMR) has been recently described as an alternative to endoscopic mucosal resection (EMR) for flat colorectal polyps. However, the real applications remain unclear due to the lack of comparative studies. Methods: a multi-centric prospective study was performed from November 2016 to December 2017. All lesions larger than 15 mm that were resected with both techniques were included in the study. The samples were matched using the size, morphology, site and access (SMSA) score as a reference. The efficacy, efficiency and adverse events rates were compared. Results: a total of 162 resections were collected (112 EMR and 50 U-EMR) with an average size of 25 mm. U-EMR achieved better results for the en bloc resection rate (49 vs 62%; p = 0.08) and there were no cases of an incomplete resection (10.7 vs 0%; p = 0.01). U-EMR was faster than EMR and there were no differences in the adverse events rate. Furthermore, U-EMR tended to achieve better results in terms of recurrence. Performing the resection in emersion appeared to prevent the cautery artefact, especially in sessile serrated adenomas. Conclusion: in the real clinical practice, U-EMR and EMR are equivalent in terms of efficacy and safety. Furthermore, U-EMR may be a feasible approach to prevent cautery artefact, allowing an accurate pathologic assessment

No disponible

Short and long-term outcomes of underwater EMR compared to the traditional procedure in the real clinical practice.

BACKGROUND AND AIMS: underwater endoscopic mucosal resection (U-EMR) has been recently described as an alternative to endoscopic mucosal resection (EMR) for flat colorectal polyps. However, the real applications remain unclear due to the lack of comparative studies. METHODS: a multi-centric prospective study was performed from November 2016 to December 2017. All lesions larger than 15 mm that were resected with both techniques were included in the study. The samples were matched using the size, morphology, site and access (SMSA) score as a reference. The efficacy, efficiency and adverse events rates were compared. RESULTS: a total of 162 resections were collected (112 EMR and 50 U-EMR) with an average size of 25 mm. U-EMR achieved better results for the en bloc resection rate (49 vs 62%; p = 0.08) and there were no cases of an incomplete resection (10.7 vs 0%; p = 0.01). U-EMR was faster than EMR and there were no differences in the adverse events rate. Furthermore, U-EMR tended to achieve better results in terms of recurrence. Performing the resection in emersion appeared to prevent the cautery artefact, especially in sessile serrated adenomas. CONCLUSION: in the real clinical practice, U-EMR and EMR are equivalent in terms of efficacy and safety. Furthermore, U-EMR may be a feasible approach to prevent cautery artefact, allowing an accurate pathologic assessment.

Cranial Pair 0: The Nervus Terminalis.

Originally discovered in elasmobranchs by Fritsh in 1878, the nervus terminalis has been found in virtually all species, including humans. After more than one-century debate on its nomenclature, it is nowadays recognized as cranial pair zero. The nerve mostly originates in the olfactory placode, although neural crest contribution has been also proposed. Developmentally, the nervus terminalis is clearly observed in human embryos; subsequently, during the fetal period loses some of its ganglion cells, and it is less recognizable in adults. Fibers originating in the nasal cavity passes into the cranium through the middle area of the cribiform plate of the ethmoid bone. Intracranially, fibers joint the telencephalon at several sites including the olfactory trigone and the primordium of the hippocampus to reach preoptic and precommissural regions. The nervus terminalis shows ganglion cells, that sometimes form clusters, normally one or two located at the base of the crista galli, the so-called ganglion of the nervus terminalis. Its function is uncertain. It has been described that its fibers facilitates migration of luteinizing hormone-releasing hormone cells to the hypothalamus thus participating in the development of the hypothalamic-gonadal axis, which alteration may provoke Kallmann's syndrome in humans. This review summarizes current knowledge on this structure, incorporating original illustrations of the nerve at different developmental stages, and focuses on its anatomical and clinical relevance. Anat Rec, 302:394-404, 2019. © 2018 Wiley Periodicals, Inc.

Thrombotic microangiopathy and accelerated hypertension after treatment with interferon beta / Microangiopatía trombótica e hipertensión acelerada tras tratamiento con interferón beta

No disponible

Personas usuarias del servicio de ayuda a domicilio. Una mirada desde la vulnerabilidad y la fragilidad / Users of the home help service. A view from the vulnerability and frailty

Introducción: El trabajo que se presenta tiene como objetivo profundizar en el conocimiento de la situación de fragilidad y vulnerabilidad de las personas atendidas en su hogar por el Servicio de Ayuda a Domicilio en Andalucía (SAD), para mejorar las intervenciones que se realizan y detectar posibles necesidades no cubiertas. Metodología: Se han recogido datos de una muestra representativa de 391 personas mayores a través de un cuestionario elaborado para este estudio. Se han incluido variables sociodemográficas, apoyo familiar, problemas de salud, necesidades atendidas y no atendidas y entorno. Resultados: El perfil de usuario del SAD es mujer, de 81 años, con bajo nivel educativo cuya fuente principal de ingresos es una pensión. Vive con su cónyuge en un domicilio que tiene algunos problemas de accesibilidad y utiliza dispositivos de apoyo para la movilidad. Presenta problemas de salud crónicos y tiene un sentimiento de soledad. Conclusiones: A pesar de que el SAD cubre múltiples necesidades que tienen las personas mayores, se han detectado una serie de lagunas en algunas áreas y necesidades de mejora en la coordinación entre el ámbito sanitario y social

Introduction: The work presented aims to deepen the understanding of the situation of fragility and vulnerability of the person cared for in home help service in Andalusia, to improve interventions carried out and to detect possible needs not covered. Methods: We have collected data from a representative sample of 391 older people through a questionnaire developed for this study. We have included socio-demographic variables, support family, problems of health, served and unmet needs and environment. Results: The user profile of home help service is as follows: woman, 81 years, with low level of education whose main source of income is a pension. She lives with her spouse in a domicile, with some problems of accessibility and she uses assistive mobility devices. She has chronic health problems and has a feeling of loneliness. Conclusions: While the home help service covers a multiple needs of older persons, they have been detected a number of gaps in some areas and needs for improvement in the coordination between the health and social fields