Characterization of Carotid Smooth Muscle Cells during Phenotypic Transition.

Vascular smooth muscle cells (VSMCs) are central players in carotid atherosclerosis plaque development. Although the precise mechanisms involved in plaque destabilization are not completely understood, it is known that VSMC proliferation and migration participate in plaque stabilization. In this study, we analyzed expression patterns of genes involved in carotid atherosclerosis development (e.g., transcription factors of regulation of SMC genes) of VSMCs located inside or outside the plaque lesion that may give clues about changes in phenotypic plasticity during atherosclerosis. VSMCs were isolated from 39 carotid plaques extracted from symptomatic and asymptomatic patients by endarterectomy. Specific biomarker expression, related with VSMC phenotype, was analyzed by qPCR, western immunoblot, and confocal microscopy. MYH11, CNN1, SRF, MKL2, and CALD1 were significantly underexpressed in VSMCs from plaques compared with VSMCs from a macroscopically intact (MIT) region, while SPP1, KLF4, MAPLC3B, CD68, and LGALS3 were found significantly upregulated in plaque VSMCs versus MIT VSMCs. The gene expression pattern of arterial VSMCs from a healthy donor treated with 7-ketocholesterol showed high similarity with the expression pattern of carotid plaque VSMCs. Our results indicate that VSMCs isolated from plaque show a typical SMC dedifferentiated phenotype with macrophage-like features compared with VSMCs isolated from a MIT region of the carotid artery. Additionally, MYH11, KLF5, and SPP1 expression patterns were found to be associated with symptomatology of human carotid atherosclerosis.

RNAseq based transcriptomics study of SMCs from carotid atherosclerotic plaque: BMP2 and IDs proteins are crucial regulators of plaque stability.

Carotid artery atherosclerosis is a risk factor to develop cerebrovascular disease. Atheroma plaque can become instable and provoke a cerebrovascular event or else remain stable as asymptomatic type. The exact mechanism involved in plaque destabilization is not known but includes among other events smooth muscle cell (SMC) differentiation. The goal of this study was to perform thorough analysis of gene expression differences in SMCs isolated from carotid symptomatic versus asymptomatic plaques. Comparative transcriptomics analysis of SMCs based on RNAseq technology identified 67 significant differentially expressed genes and 143 significant differentially expressed isoforms in symptomatic SMCs compared with asymptomatic. 37 of top-scoring genes were further validated by digital PCR. Enrichment and network analysis shows that the gene expression pattern of SMCs from stable asymptomatic plaques is suggestive for an osteogenic phenotype, while that of SMCs from unstable symptomatic plaque correlates with a senescence-like phenotype. Osteogenic-like phenotype SMCs may positively affect carotid atheroma plaque through participation in plaque stabilization via bone formation processes. On the other hand, plaques containing senescence-like phenotype SMCs may be more prone to rupture. Our results substantiate an important role of SMCs in carotid atheroma plaque disruption.

The use of unenhanced Doppler sonography in the evaluation of solid breast lesions.

OBJECTIVE: The objectives of our study were to investigate differences in Doppler sonography features between benign and malignant breast lesions and between malignant lesions with different prognostic factors and to propose diagnostic criteria for Doppler sonography of breast lesions. SUBJECTS AND METHODS: We performed power and duplex Doppler sonography examinations in 826 breast lesions scheduled for sonographically guided core needle biopsy. Lesion vascularity, pulsatility index (PI), and resistive index (RI) of the vessels detected were analyzed and correlated with histologic results. RESULTS: Color flow was more frequently seen in malignant (237/348 lesions, 68%) than in benign (171/478, 36%) lesions (p < 0.001). However, sensitivity, specificity, and positive and negative predictive values for this sign were low (68%, 64%, 58%, and 73%, respectively). The RI and PI values were significantly higher (p < 0.001) in cancers. Although an overlap in these values between benign and malignant lesions was observed, all but one nodule with an RI of greater than 0.99 (those with null or inverted diastolic flow) or a PI of greater than 4 were malignant. No significant relationship was found between PI, RI, or flow visualization on power Doppler sonography and tumor grade or lymph node involvement in cancers. CONCLUSION: Flow visualization on power Doppler sonography indicates a higher possibility of malignancy but is not useful as the main sign for malignancy. However, any lesion with a vessel that has an RI value greater than 0.99 or a PI value greater than 4 within it must be considered as probably malignant regardless of any other sonography sign present. Doppler findings are not useful to predict tumor grade or lymph node involvement.

Tomografía computarizada con contraste rectal en el diagnóstico de la apendicitis aguda / Rectal contrast-enhanced computed tomography in the diagnosis of acute appendicitis

Objetivo: Valorar la eficacia y la utilidad de la tomografía computarizada (TC) en el diagnóstico de la apendicitis. Evaluar la fiabilidad de los signos de diagnóstico y de exclusión de apendicitis en la TC de fosa ilíaca derecha.Material y métodos: Durante un año, se estudiaron mediante TC 152 pacientes con sospecha clínica de apendicitis. Las exploraciones fueron interpretadas por dos radiólogos que valoraron la existencia de un apéndice normal o engrosado, y de otros signos de apendicitis, emitiendo un diagnóstico positivo o negativo para apendicitis. Los diagnósticos finales se establecieron por cirugía o seguimiento clínico.Resultados: La TC obtuvo para el diagnóstico de apendicitis una sensibilidad del 81,8 por ciento, una especificidad del 95,3 por ciento, un valor predictivo positivo del 93,1 por ciento, un valor predictivo negativo del 87,2 por ciento y una fiabilidad del 89,9 por ciento. Los signos de apendicitis observados fueron: apendicolitos (30,3 por ciento de sensibilidad, 98,8 por ciento de especificidad), colecciones líquidas (19,7 por ciento y 96,5 por ciento), engrosamiento cecal (21,2 por ciento y 97,7 por ciento), inflamación de la grasa pericecal (72,7 por ciento y 90,7 por ciento), engrosamiento fascial (48,5 por ciento y 91,9 por ciento), y apéndice mayor de 6 mm (78,8 por ciento y 94,2 por ciento). Adenopatías y líquido libre peritoneal no presentaron relación significativa con apendicitis. Visualizar un apéndice normal relleno de aire o contraste mostró un alto valor predictivo negativo para la apendicitis. En 35 de 94 casos con TC negativa se propusieron diagnósticos alternativos.Conclusiones: La TC es altamente fiable en la apendicitis. Un apéndice relleno de aire y/o contraste es un signo de elevado valor predictivo negativo. La visualización de apendicolitos tiene un elevado valor predictivo positivo (AU)