Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency

BACKGROUND: In newborn screening with tandem mass spectrometry, multiple intermediary metabolites are quantified in a single analytical run for the diagnosis of fatty-acid oxidation disorders, organic acidurias, and aminoacidurias. Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the markers have been chosen to reflect metabolic pathway deviations. METHODS: We applied a procedure to extract new markers and diagnostic criteria for newborn screening to the data of newborns with confirmed medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and a control group from the newborn screening program, Heidelberg, Germany. We validated the results with external data of the screening center in Hamburg, Germany. We extracted new markers by performing a systematic search for analyte combinations (features) with high discriminatory performance for MCADD. To select feature thresholds, we applied automated procedures to separate controls and cases on the basis of the feature values. Finally, we built classifiers from these new markers to serve as diagnostic criteria in screening for MCADD. RESULTS: On the basis of chi(2) scores, we identified approximately 800 of >628,000 new analyte combinations with superior discriminatory performance compared with the best published combinations. Classifiers built with the new features achieved diagnostic sensitivities and specificities approaching 100%. CONCLUSION: Feature construction methods provide ways to disclose information hidden in the set of measured analytes. Other diagnostic tasks based on high-dimensional metabolic data might also profit from this approach.     

Laser-induced interstitial thermotherapy of liver metastases in an interventional 0.5 Tesla MRI system: technique and first clinical experiences

Laser-induced interstitial thermotherapy (LITT) surveyed by magnetic resonance imaging (MRI) has been shown to be effective in various applications. The laser treatment of colorectal liver metastases usually requires a separate device (e.g., ultrasound or CT) to position the laser applicator. In this study, we used an interventional 0.5 T MRI system, allowing both the navigation to the target tissue and on-line thermometry. Laser irradiation was performed using a near-infrared laser source combined with a cooled laser light guide. We treated 20 patients exhibiting a total of 58 colorectal liver metastases. Clinically relevant complications did not occur. No residual tumor was observed after laser irradiation in all metastases with a diameter below 2 cm. Metastases with a mean diameter between 2 and 3 cm demonstrated total necrosis in 71%, while in larger tumors this proportion decreased to 46% (diameter, 3-4 cm) and 30% (diameter, >4 cm), respectively. We conclude that LITT, guided by the employed interventional MRI system, is feasible and safe. The results suggest a more aggressive treatment, especially for larger metastases. J. Magn. Reson. Imaging 2001;13:729-737.     

MR-guided laser irradiation of recurrent glioblastomas

We treated two patients with recurrent glioblastoma multiforme using Nd:YAG laser irradiation in the framework of a salvage therapy. The underlying concept is to achieve cytoreduction by partial coagulation of the tumor. Magnetic resonance imaging (MRI) follow-up examinations revealed a volume reduction of the laser-irradiated areas, while the untreated parts of the tumor exhibited a progression. The survival time after the diagnosis of the recurrence was 16 and 20 months, respectively, which is substantially (about four times) longer than the natural history of the disease would suggest. In conclusion, cytoreduction by laser irradiation may be a promising option for patients suffering from recurrent glioblastoma multiforme. Future work should optimize the therapeutic regimen and evaluate this treatment approach in controlled clinical trials.     

Hemoadsorption with CytoSorb® and the early course of linezolid plasma concentration during septic shock

Journal of Artificial Organs - Hemoadsorption with CytoSorb® becomes increasingly established in treatment of various, predominantly inflammation-associated diseases. In septic shock, results...