Voriconazole exposure and the risk of cutaneous squamous cell carcinoma in allogeneic hematopoietic stem cell transplant patients.

BACKGROUND: Voriconazole is a commonly used antifungal medication in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. In solid organ transplantation, voriconazole use has been associated with the development of cutaneous squamous cell carcinoma (SCC). We sought to determine if voriconazole use was associated with SCC in patients undergoing allo-HSCT. METHODS: We retrospectively reviewed consecutive adult patients who underwent allo-HSCT at Mayo Clinic from January 2007 through July 2012. Multivariable Cox models were created to assess the relationship of SCC with two time-dependent voriconazole exposure variables: (i) history of voriconazole exposure (yes/no), and (ii) cumulative days of voriconazole use. RESULTS: In our cohort of 381 allo-HSCT patients, SCC developed in 26 of 312 patients exposed to voriconazole (25 post-voriconazole) and in 1 of 69 patients who received alternative antifungal agent(s). Cumulative incidence of SCC was estimated to be 19% at 5 years post allo-transplant. Cumulative days of voriconazole use was found to be a risk factor for SCC, and this relationship persisted in a multivariable model using previously identified risk factors as covariates (hazard ratio 1.859 for each 180 days of use, P < 0.001). CONCLUSION: This is the first study, to our knowledge, to identify cumulative days of voriconazole use as a risk factor for SCC development following allo-HSCT, and may help guide appropriate antifungal use in this patient population.

The mean A beta load in the hippocampus correlates with duration and severity of dementia in subgroups of Alzheimer disease.

Using image analysis techniques to quantify the percentage area covered by the immunopositive marker for amyloid beta-peptide (A beta), we examined subjects with combinations of either early-onset or late-onset Alzheimer disease (AD) and either familial Alzheimer disease (FAD) or sporadic Alzheimer disease (SAD). We measured the mean and maximum A beta loads, in the hippocampus of each subject. There were no statistically significant differences in the mean A beta load between familial and sporadic AD subjects. Although sample sizes were too small for statistical testing, subjects with the epsilon 4/epsilon 4 allele of the apolipoprotein E (ApoE) gene had higher mean A beta loads than those with the epsilon 3/epsilon 3 or epsilon 3/epsilon 4 alleles. Members of the Volga German families (recently linked to chromosome 1) all had high mean A beta loads, and one of the chromosome 14-linked subjects had the highest mean A beta load while the other had a relatively small load, but the sample was too small for statistical comparisons. The duration of dementia and neuropsychological test scores showed a statistically significant correlation with the mean A beta load in the hippocampus, but not with the maximum A beta load. This difference indicates that the mean A beta load may be a more useful feature than the maximum A beta load as an objective neuropathological measure for cognitive status. This finding may help to improve the established methods for quantitative assessment of the neuropathological changes in AD.

A mathematical model of glioma growth: the effect of chemotherapy on spatio-temporal growth.

During the past two decades computerized tomography (CT) and magnetic resonance imaging (MRI) have permitted the detection of tumours at much earlier stages in their development than was previously possible. In spite of this earlier diagnosis the effects of earlier and more extensive treatments have been difficult to document. This failure has led to an increasing awareness of the importance of infiltration of glioma cells into surrounding grossly normal brain tissue such that recurrence still occurs. In this paper a simple mathematical model for the proliferation and infiltration of such tumours is introduced, based in part on quantitative image analysis of histological sections of a human brain glioma and especially on cross-sectional area/volume measurements of serial CT images while the patient was undergoing chemotherapy. The model parameters were estimated using optimization techniques to give the best fit of the simulated tumour area to the CT scan data. Numerical solution of the model on a two-dimensional domain, which took into account the geometry of the brain and its natural barriers to diffusion, was used to determine the effect of chemotherapy on the spatio-temporal growth of the tumour.

Automated prescreening of conventionally prepared cervical smears: a feasibility study.

The feasibility of an automated screening device that will analyze conventionally prepared cervical smears was examined. Consecutive normal and abnormal cervical smears were selected retrospectively and analyzed on a customized microscope imaging workstation system. Specialized image processing, feature extraction, and object classification algorithms were integrated on the imaging workstation to provide an Analysis Score for each slide analyzed. A threshold was set for the Analysis Score, and all slides with a score less than the threshold were classified as normal. Examination of the distribution of the Analysis Score for normal and abnormal cervical smears provided an estimate that 50% of all slides will be sorted as normal, and consequently need no cytologist review. With the Analysis Score threshold set for a 50% sort rate, zero false-negative slides were found in this slide set. This study has shown that a large percentage of slides can be correctly classified as normal while maintaining a high sensitivity to abnormal slides. Given the current workload problems in cytology laboratories, reducing the screening workload by one half will be beneficial. This study has shown that it is now feasible with current technology to provide a clinically useful device to automate screening of conventional cervical smears.