RESUMEN
PURPOSE: To determine the correlation of the T1-weighted signal intensity ratio (T1 SIR, or T1 Score) and arterial-to-delayed venous enhancement ratio (ADV ratio) of the pancreas with pancreatic fibrosis on histopathology. METHODS: Sixty consecutive adult CP patients who had an MRI/MRCP study prior to pancreatic surgery were analyzed. Three blinded observers measured T1 SIR of pancreas to spleen (T1 SIR p/s), pancreas-to-paraspinal muscle (T1 SIR p/m), ADV ratio, and Cambridge grade. Histopathologic grades were given by a gastrointestinal pathologist using Ammann's fibrosis score. Statistical analysis included Spearman's correlation coefficient of the T1 SIR, ADV ratio, Cambridge grade with the fibrosis score, and weighted kappa for interobserver agreement. RESULTS: The study population included 31 female and 29 male patients, with an average age of 52.1 (26-78 years). Correlations between fibrosis score and T1 SIR p/s, T1 SIR p/m, and ADV ratio were ρ = - 0.54 (p = 0.0001), ρ = - 0.19 (p = 0.19), and ρ = - 0.39 (p = 0.003), respectively. The correlation of Cambridge grade with fibrosis score was ρ = 0.26 (p = 0.07). There was substantial interobserver agreement (weighted kappa) for T1 SIR p/s (0.78), T1 SIR p/m (0.71), and ADV ratio (0.64). T1 SIR p/s of ≤ 1.20 provided a sensitivity of 74% and specificity of 50% (AUC: 0.74), while ADV ratio of ≤ 1.10 provided a sensitivity of 75% and specificity of 55% (AUC: 0.68) to detect a fibrosis score of ≥ 6. CONCLUSION: There is a moderate negative correlation between the T1 Score (SIR p/s) and ADV ratio with pancreatic fibrosis and a substantial interobserver agreement. These parenchymal metrics show a higher correlation than the Cambridge grade.
Asunto(s)
Benchmarking , Enfermedades Pancreáticas , Adulto , Femenino , Fibrosis , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Páncreas/diagnóstico por imagen , Páncreas/patología , Enfermedades Pancreáticas/diagnóstico por imagenRESUMEN
Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders.
Asunto(s)
Oído Interno/patología , Células Ciliadas Auditivas Internas/patología , Proteínas de la Membrana/genética , Organoides/citología , Serina Proteasas/genética , Animales , Apoptosis/genética , Membrana Celular/metabolismo , Codón sin Sentido , Técnicas de Inactivación de Genes , Homeostasis/genética , Humanos , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Mecanotransducción Celular , Proteínas de la Membrana/metabolismo , Ratones , Análisis de Secuencia de ARN , Serina Proteasas/metabolismo , Análisis de la Célula IndividualRESUMEN
OBJECTIVES: To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration. STUDY DESIGN: Institutional review board-approved prospective cohort study. METHODS: Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified. RESULTS: Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 µm2 vs. 66 ± 8 µm2 ; P < 0.05) and 4 mm diameter (70 ± 8 µm2 vs. 50 ± 3 µm2 ; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/µg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/µg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips. CONCLUSION: Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E41-E46, 2018.