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PURPOSE OF REVIEW: Isocitrate dehydrogenase wild-type glioblastoma is the most aggressive primary brain tumour in adults. Its infiltrative nature and heterogeneity confer a dismal prognosis, despite multimodal treatment. Precision medicine is increasingly advocated to improve survival rates in glioblastoma management; however, conventional neuroimaging techniques are insufficient in providing the detail required for accurate diagnosis of this complex condition. RECENT FINDINGS: Advanced magnetic resonance imaging allows more comprehensive understanding of the tumour microenvironment. Combining diffusion and perfusion magnetic resonance imaging to create a multiparametric scan enhances diagnostic power and can overcome the unreliability of tumour characterisation by standard imaging. Recent progress in deep learning algorithms establishes their remarkable ability in image-recognition tasks. Integrating these with multiparametric scans could transform the diagnosis and monitoring of patients by ensuring that the entire tumour is captured. As a corollary, radiomics has emerged as a powerful approach to offer insights into diagnosis, prognosis, treatment, and tumour response through extraction of information from radiological scans, and transformation of these tumour characteristics into quantitative data. Radiogenomics, which links imaging features with genomic profiles, has exhibited its ability in characterising glioblastoma, and determining therapeutic response, with the potential to revolutionise management of glioblastoma. The integration of deep learning algorithms into radiogenomic models has established an automated, highly reproducible means to predict glioblastoma molecular signatures, further aiding prognosis and targeted therapy. However, challenges including lack of large cohorts, absence of standardised guidelines and the 'black-box' nature of deep learning algorithms, must first be overcome before this workflow can be applied in clinical practice.
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ABSTRACT: The presence or absence of tissue eosinophilia has previously aided in the diagnosis of inflammatory skin conditions. However, recent studies have elucidated the presence of eosinophils in traditionally eosinophil-poor inflammatory skin diseases, such as dermatomyositis (DM), psoriasis, and lichen sclerosus (LS). This systematic review of the literature explores previous studies of tissue eosinophilia in skin biopsies of dermatoses that are believed to be classically poor in eosinophil. We identified 26 studies, the majority of which were retrospective reviews. The percent of specimens with increased eosinophils in psoriasis ranged from 18%-73%, pityriasis rubra pilaris (PRP) 22%-63%, LS 29%-53%, DM 15%-44%, morphea 8%-45%, hypertrophic lichen planus (LP) 0%-21%, and oral LP 0%-4%. These reports of tissue eosinophilia in reputed eosinophil-poor dermatologic conditions present a diagnostic pitfall and suggest that tissue eosinophilia itself should not be used to rule out a diagnosis of one of these conditions.
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Eosinofilia , Liquen Escleroso y Atrófico , Pitiriasis Rubra Pilaris , Psoriasis , Humanos , Eosinofilia/patología , Eosinófilos/patología , Liquen Escleroso y Atrófico/patología , Pitiriasis Rubra Pilaris/patología , Psoriasis/patología , Estudios Retrospectivos , Piel/patologíaRESUMEN
Dermatomyositis is an idiopathic inflammatory myopathy that often presents with symmetric proximal skeletal muscle weakness and characteristic skin findings. Typical skin biopsy findings include vacuolar changes of the basal layer, increased dermal mucin, and a predominantly lymphocytic infiltrate. We report a case of dermatomyositis presenting as intensely pruritic papules and plaques, with initial histopathology being atypical of dermatomyositis due to the presence of eosinophils. The initial biopsy demonstrated a superficial dermatitis with eosinophils, initially thought to represent a drug eruption. A second biopsy of the same cutaneous manifestation was performed at a later time given high clinical suspicion for dermatomyositis and demonstrated a more classic vacuolar interface dermatitis with increased mucin and an absence of eosinophils. Notably, increased pruritus was specifically associated with the lesion that demonstrated tissue eosinophilia. The case illustrates the importance of considering tissue eosinophilia in the histologic presentation of dermatomyositis.
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Rectal cancer is an increasing disease worldwide. The outcomes of its treatment are related to the preoperative characteristics of the patient. The objective of this study was to describe sociodemographic, clinical and surgical characteristics and outcomes of patients operated on for rectal cancer at Hospital Universitario Mayor Méderi (HUM) during the period within 2013-2017.A retrospective descriptive cohort-type study was carried out by consulting the clinical records of patients above the age of 18 years with a clinical/histopathological diagnosis of rectal cancer and an institutional follow-up in those who underwent surgery with laparoscopic anterior resection of the rectum carried out by the coloproctology service of the HUM between 2013 and 2017. For statistical analysis, the SPSS V22 program was used.Data from 133 patients were collected during the study period, most of them male, with more frequent involvement of the lower rectum. Complications occurred in 25% of the patients. Conversion rate to open surgery was 8.6%, in-hospital death was associated with cardiovascular comorbidity, corticosteroid uses and with the presence of complications. Sociodemographic characteristics of the patients were similar to the world population. The institution has a low prevalence of anastomotic dehiscence, global complications are comparable with international statistics.
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Hospitales , Neoplasias del Recto , Humanos , Masculino , Adolescente , Colombia/epidemiología , Estudios Retrospectivos , Mortalidad Hospitalaria , Neoplasias del Recto/cirugíaRESUMEN
Vulvar disease is common, and urologists are often the first providers to see patients with a vulvar skin condition. Primary vulvar dermatoses can be localized to the anogenital area or a manifestation of more diffuse cutaneous disease. Additionally, secondary dermatoses can develop from exogenous agents and inflammatory vaginitis. Vulvar conditions are challenging to diagnose due to location and different types of skin and mucosal epithelium involved. Herein, we provide an overview of noninfectious inflammatory vulvar dermatoses (part I) and benign and malignant vulvar neoplasms (part II), grouped by morphologic findings. We include diagnostic evaluation, workup, and management of these conditions.
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Enfermedades de la Piel , Enfermedades de la Vulva , Neoplasias de la Vulva , Femenino , Humanos , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/patología , Enfermedades de la Vulva/diagnóstico , Enfermedades de la Vulva/patología , Enfermedades de la Vulva/terapia , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/terapiaRESUMEN
Vulvar disease is common, and urologists are often the first providers to see patients with a vulvar skin condition. Primary vulvar dermatoses can be localized to the anogenital area or a manifestation of more diffuse cutaneous disease. Additionally, secondary dermatoses can develop from exogenous agents and inflammatory vaginitis. Vulvar conditions are challenging to diagnose due to location and different types of skin and mucosal epithelium involved. Herein, we provide an overview of noninfectious inflammatory vulvar dermatoses (Part I) and benign and malignant vulvar neoplasms (Part II), grouped by morphologic findings. We include diagnostic evaluation, workup, and management of these conditions.
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Neoplasias Cutáneas , Enfermedades de la Vulva , Neoplasias de la Vulva , Femenino , Humanos , Piel/patología , Neoplasias Cutáneas/patología , Vulva/patología , Enfermedades de la Vulva/diagnóstico , Enfermedades de la Vulva/patología , Enfermedades de la Vulva/terapia , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/terapiaRESUMEN
Chronic cellular stress associated with neurodegenerative disease can result in the persistence of stress granule (SG) structures, membraneless organelles that form in response to cellular stress. In Huntington's disease (HD), chronic expression of mutant huntingtin generates various forms of cellular stress, including activation of the unfolded protein response and oxidative stress. However, it has yet to be determined whether SGs are a feature of HD neuropathology. We examined the miRNA composition of extracellular vesicles (EVs) present in the cerebrospinal fluid (CSF) of patients with HD and show that a subset of their target mRNAs were differentially expressed in the prefrontal cortex. Of these targets, SG components were enriched, including the SG-nucleating Ras GTPase-activating protein-binding protein 1 (G3BP1). We investigated localization and levels of G3BP1 and found a significant increase in the density of G3BP1-positive granules in the cortex and hippocampus of R6/2 transgenic mice and in the superior frontal cortex of the brains of patients with HD. Intriguingly, we also observed that the SG-associated TAR DNA-binding protein 43 (TDP43), a nuclear RNA/DNA binding protein, was mislocalized to the cytoplasm of G3BP1 granule-positive HD cortical neurons. These findings suggest that G3BP1 SG dynamics may play a role in the pathophysiology of HD.
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Gránulos Citoplasmáticos/metabolismo , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Hipocampo/metabolismo , Enfermedad de Huntington/metabolismo , Neuronas/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Corteza Prefrontal/metabolismo , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Animales , Gránulos Citoplasmáticos/patología , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Femenino , Hipocampo/patología , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Masculino , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Neuronas/patología , Proteínas de Unión a Poli-ADP-Ribosa/genética , Corteza Prefrontal/patología , Transporte de Proteínas/genética , ARN Helicasas/genética , Proteínas con Motivos de Reconocimiento de ARN/genéticaRESUMEN
BACKGROUND: Biochemical analysis of mutant huntingtin (mHTT) aggregation species in HD mice is a common measure to track disease. A longitudinal and systematic study of how tissue processing affects detection of conformers has not yet been reported. Understanding the homeostatic flux of mHTT over time and under different processing conditions would aid in interpretation of pre-clinical assessments of disease interventions. OBJECTIVE: Provide a systematic evaluation of tissue lysis methods and molecular and biochemical assays in parallel with behavioral readouts in R6/2 mice to establish a baseline for HTT exon1 protein accumulation. METHODS: Established biochemical methods were used to process tissue from R6/2 mice of specific ages following behavior tasks. Aggregation states and accumulation of mHTT exon 1 protein were evaluated using multiple break and assay methods to determine potential conformational flux assay specificity in detection of mHTT species, and tissue specificity of conformers. RESULTS: Detection of mHTT exon 1 protein species varied based on biochemical processing and analysis providing a baseline for subsequent studies in R6/2 mice. Insoluble, high molecular weight species of mHTT exon 1 protein increased and tracked with onset of behavioral impairments in R6/2 mice using multiple assay methods. CONCLUSIONS: Conformational flux from soluble monomer to high molecular weight, insoluble species of mHTT exon 1 protein was generally consistent for multiple assay methods throughout R6/2 disease progression; however, the results support the use of multiple biochemical techniques to detect mHTT exon 1 protein species for preclinical assessments in HD mouse models expressing mHTT exon 1 protein.
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Encéfalo/metabolismo , Proteína Huntingtina/metabolismo , Agregación Patológica de Proteínas/metabolismo , Animales , Modelos Animales de Enfermedad , Electroforesis en Gel de Agar , Electroforesis en Gel de Poliacrilamida , Exones , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/metabolismo , Estudios Longitudinales , Ratones , Ratones Endogámicos , Ratones Transgénicos , Manejo de EspecímenesRESUMEN
Resumen El Tumor Venéreo Transmisible (TVT), es una neoplasia común de la especie canina, se localiza principalmente en la mucosa de los genitales; es altamente contagiosa y es la única que puede ser transmisible mediante el trasplante celular por contacto directo. Se diagnostica por estudio citológico y su tratamiento es la quimioterapia con sulfato de vincristina, fármaco de elección por tener un alto porcentaje de efectividad y baja recidiva; sin embargo, se han descrito efectos adversos como trastornos digestivos, hemáticos y nerviosos por parte de la población tratada. El objetivo de este trabajo es dar a conocer la efectividad y comportamiento de otras alternativas para el tratamiento de TVT; primero con un protocolo de autohemoterapia y el otro mediante la inmunoterapia con ácido yatrénico mas caseína, que actúan sobre el sistema inmunológico del animal, haciendo que sea el mismo organismo quien realice la eliminación del tumor.
Abstract Transmissible Venereal Tumor (TVT) is a common canine neoplasia; it is mainly located in the genital mucosa. This pathology is highly contagious and can be transmitted by direct contact cell transplantation from a diseased to a non-diseased mucosa. It is primarily diagnosed by cytology and its treatment is chemotherapy being the vincristine sulfate the medicine of choice. The Vincristine has a high rate of effectiveness and low recidivism; however, this alternative has important side effects. The treatment with Vincristine could cause primarily digestive upset, hematological, and nervous diseases. The objective of this work is to determine the efficacy and performance of alternative therapies for the treatment of TVT, firstly, with an autohemoterapy protocol, and using an immunotherapy treatment with yatrenic acid and casein, which acts in the animal's immune system and causes the same organism to eradicate the tumor.
Resumo O Tumor Venéreo Transmissível (TVT), é uma neoplasia comum da espécie canina, localiza-se principalmente na mucosa dos genitais; é altamente contagioso e é o único que pode ser transmitido por transplante de células de contato direto. É diagnosticado por estudo citológico e seu tratamento é a quimioterapia com sulfato de vincristina, a droga de escolha por apresentar alto percentual de eficácia e baixa recorrência; entretanto, efeitos adversos como distúrbios digestivos, sanguíneos e nervosos foram relatados na população tratada. O objetivo deste trabalho é apresentar a eficácia e o comportamento de outras alternativas para o tratamento do TVT; a primeira com um protocolo de auto-hemoterapia e a outra por meio de imunoterapia com ácido yatrênico mais caseína, que atuam no sistema imunológico do animal, fazendo com que o mesmo organismo realize a retirada do tumor.