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Wrist Mycobacterium tuberculosis (TB) complex osteomyelitis is rare, with polymicrobial TB osteomyelitis even more uncommon. The authors describe an unusual case of polymicrobial TB wrist osteomyelitis. The case patient presented with a 2.5-year history of 2 insidiously growing nodules on his wrist. He underwent debridement, and tissue cultures grew methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, and, later, TB complex. He was started on vancomycin, rifampin, isoniazid, pyrazinamide, and ethambutol with improvement in symptoms. This case emphasizes the importance of a broad differential and thorough workup for atypical presentations of osteomyelitis. Diagnosis of uncommon etiologies is essential for definitive treatment.
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Purpose: Recently, the association between ATRX and a more aggressive sarcoma phenotype has been shown. We performed a retrospective study of sarcomas from an individual institution to evaluate ATRX as a prognosticator in soft tissue sarcoma. Experimental Design. 128 sarcomas were collected from a single institution and stained for ATRX. The prognostic significance of these markers was evaluated in a smaller cohort of primary soft tissue sarcomas (n = 68). Kaplan-Meier curves were created for univariate analysis, and Cox regression was utilized for multivariate analysis. Results: High expression of ATRX was found to be a positive prognostic indicator for overall survival and metastasis-free survival in our group of soft tissue sarcomas both in univariate analysis and multivariate analysis (HR: 0.38 (0.17-0.85), P=0.02 and HR: 0.49 (0.24-0.99), P=0.05, respectively). Conclusions: High expression of ATRX is a positive prognostic indicator of overall survival and metastasis-free survival in patients with STS. This is consistent with studies in osteosarcoma, which indicate possible mechanisms through which loss of ATRX leads to more aggressive phenotypes. Future prospective clinical studies are required to validate the prognostic significance of these findings.
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CIC::DUX4 sarcoma (CDS) is a rare but highly aggressive undifferentiated small round cell sarcoma driven by a fusion between the tumor suppressor Capicua (CIC) and DUX4. Currently, there are no effective treatments and efforts to identify and translate better therapies are limited by the scarcity of patient tumor samples and cell lines. To address this limitation, we generated three genetically engineered mouse models of CDS (Ch7CDS, Ai9CDS, and TOPCDS). Remarkably, chimeric mice from all three conditional models developed spontaneous soft tissue tumors and disseminated disease in the absence of Cre-recombinase. The penetrance of spontaneous (Cre-independent) tumor formation was complete irrespective of bi-allelic Cic function and the distance between adjacent loxP sites. Characterization of soft tissue and presumed metastatic tumors showed that they consistently expressed the CIC::DUX4 fusion protein and many downstream markers of the disease credentialing the models as CDS. In addition, tumor-derived cell lines were generated and ChIP-seq was preformed to map fusion-gene specific binding using an N-terminal HA epitope tag. These datasets, along with paired H3K27ac ChIP-sequencing maps, validate CIC::DUX4 as a neomorphic transcriptional activator. Moreover, they are consistent with a model where ETS family transcription factors are cooperative and redundant drivers of the core regulatory circuitry in CDS.
Asunto(s)
Sarcoma de Células Pequeñas , Sarcoma , Neoplasias de los Tejidos Blandos , Animales , Ratones , Alelos , Biomarcadores de Tumor , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Proteínas Proto-Oncogénicas c-ets , Sarcoma/genética , Sarcoma/metabolismo , Sarcoma de Células Pequeñas/química , Sarcoma de Células Pequeñas/genética , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , HumanosRESUMEN
Objetivo: Evaluar el efecto del ejercicio físico sobre los niveles de las subpoblaciones HDL, enzima lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol en estudiantes de Medicina. Método: La población se dividió de manera voluntaria en 2 grupos: ejercicio y no ejercicio. Se midieron perímetro abdominal e índice de masa corporal, subfracciones de HDL2 y HDL3 por precipitación iónica, y enzima lecitina-colesterol acil-transferasa y proteína transportadora de ésteres de colesterol mediante Enzyme-Linked Immuno Sorbent Assay (ELISA). Resultados: El perfil lipídico de riesgo aumentó en ambos grupos: las HDL, HDL3 y HDL2 disminuyeron en ambos grupos, pero solo las HDL2 lo hicieron de forma significativa en el grupo que realizó ejercicio. La lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol permanecieron sin cambios significativos. Sin embargo, en el grupo que hizo ejercicio hubo disminución estadísticamente significativa de HDL2 y lecitina-colesterol acil-transferasa, en las mujeres. Conclusiones: El ejercicio logra modificar algunas variables como el perímetro abdominal, el índice de masa corporal y las HDL3. Estas modificaciones son dependientes del género, pero, a pesar de la intervención de 3 meses con un programa de ejercicio, este no logra reducir los factores de riesgo lipídico en esta población de estudiantes de Medicina, debido a que su entorno hace muy compleja la respuesta metabólica al ejercicio.
Objective: To evaluate exercise effect on HDL subpopulations, lecithin-cholesterol acyltransferase enzyme and ester transfer protein cholesterol levels in medical students. Method: Population was divided voluntarily into 2 groups, exercise and no exercise. Waist circumference and body mass index were measured; subfractions HDL2 and HDL3 by ion precipitation and LCAT and CETP enzymes Enzyme-Linked Immuno-Sorbent Assay (ELISA). Results: Lipidrisk profile increased in both groups; HDL, HDL2 and HDL3 decreased in both groups, but only the HDL2 decreased significantly in students who exercised. LCAT and CETP remained without significant changes, however, in the exercise group, there was statistically significant decrease in HDL2 and LCAT in women. Conclusions: This study shows that exercise does alter some variables such as waist circumference, body mass index and HDL3. These changes are dependent on gender, but despite the intervention of 3 months with an exercise program, it fails reducing lipid risk factors in this medical student populations, given their environment, which complicates their metabolic response to exercise.