Growing evidence suggests that pretransplant alpha-fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-gamma-carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow-up of 78.9 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP-L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9–6.7; P < 0.001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4–5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3–12.0; P < 0.001) when AFP ≥ 250 ng/mL and DCP ≥ 7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4–4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0–24.6; P < 0.001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8–18.1; P < 0.001) for outside the Milan criteria and DCP ≥ 7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility.
Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.
Since the successful tornado forecast at Tinker AFB in 1948 paved the way for the issuance of tornado warnings, the science of tornado detection and forecasting has advanced greatly. However, tornado warnings must be disseminated to the public to be of any use. The Texas tornado warning conferences in 1953 began to develop the framework for a modern tornado warning system and included radar detection of tornadoes, a spotter network, and improved communications between the U.S. Weather Bureau, spotters, and public officials, allowing more timely warnings and dissemination of those warnings to the public. Commercial radio and television are a main source of warnings for many, and the delivery methods on TV have changed much since 1960. NOAA Weather Radio (NWR) was launched after the 1974 Super Outbreak of tornadoes, with the most important feature being the tone alert that allowed receivers to alert people even when the radio broadcast was turned off. Today, NWR reaches most of the U.S. population, and Specific Area Message Encoding technology has improved its warning precision. Outdoor warning sirens, originally designed for use in enemy attack, were made available for use during tornado warnings around 1970. “Storm based” warnings, adopted by the National Weather Service in 2007, replaced countybased warnings and greatly reduce the warning area. As communications advances continue, tornado warnings will eventually be delivered to precise locations, using GPS and other location technology, through cellular telephones, outdoor sirens, e-mails, and digital television, in addition to NWR.
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