Genotype-phenotype correlation in pseudoxanthoma elasticum.

BACKGROUND AND AIMS: Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable phenotypic variability. We investigated the association between the ABCC6 genotype and calcification and clinical phenotypes in these different organs. METHODS: ABCC6 sequencing was performed in 289 PXE patients. Genotypes were grouped as two truncating, mixed, or two non-truncating variants. Arterial calcification mass was quantified on whole body, low dose CT scans; and peripheral arterial disease was measured with the ankle brachial index after treadmill test. The presence of pseudoxanthoma in the skin was systematically scored. Ophthalmological phenotypes were the length of angioid streaks as a measure of Bruchs membrane calcification, the presence of choroidal neovascularizations, severity of macular atrophy and visual acuity. Regression models were built to test the age and sex adjusted genotype-phenotype association. RESULTS: 158 patients (median age 51 years) had two truncating variants, 96 (median age 54 years) a mixed genotype, 18 (median age 47 years) had two non-truncating variants. The mixed genotype was associated with lower peripheral (ß: 0.39, 95%CI:-0.62;-0.17) and total (ß: 0.28, 95%CI:-0.47;-0.10) arterial calcification mass scores, and lower prevalence of choroidal neovascularizations (OR: 0.41 95%CI:0.20; 0.83) compared to two truncating variants. No association with pseudoxanthomas was found. CONCLUSIONS: PXE patients with a mixed genotype have less severe arterial and ophthalmological phenotypes than patients with two truncating variants in the ABCC6 gene. Research into environmental and genetic modifiers might provide further insights into the unexplained phenotypic variability.

Volumetric image interpretation in radiology: scroll behavior and cognitive processes.

The interpretation of medical images is a primary task for radiologists. Besides two-dimensional (2D) images, current imaging technologies allow for volumetric display of medical images. Whereas current radiology practice increasingly uses volumetric images, the majority of studies on medical image interpretation is conducted on 2D images. The current study aimed to gain deeper insight into the volumetric image interpretation process by examining this process in twenty radiology trainees who all completed four volumetric image cases. Two types of data were obtained concerning scroll behaviors and think-aloud data. Types of scroll behavior concerned oscillations, half runs, full runs, image manipulations, and interruptions. Think-aloud data were coded by a framework of knowledge and skills in radiology including three cognitive processes: perception, analysis, and synthesis. Relating scroll behavior to cognitive processes showed that oscillations and half runs coincided more often with analysis and synthesis than full runs, whereas full runs coincided more often with perception than oscillations and half runs. Interruptions were characterized by synthesis and image manipulations by perception. In addition, we investigated relations between cognitive processes and found an overall bottom-up way of reasoning with dynamic interactions between cognitive processes, especially between perception and analysis. In sum, our results highlight the dynamic interactions between these processes and the grounding of cognitive processes in scroll behavior. It suggests, that the types of scroll behavior are relevant to describe how radiologists interact with and manipulate volumetric images.

Late onset subgaleal hemorrhage infection with Streptococcus pneumoniae?

We report a case of an infected subgaleal hematoma caused by an unusual micro-organism in a previously healthy 11-month-old girl. Our patient presented at the emergency department with an increasing scalp swelling for 2 weeks, and culture of the evacuated fluid yielded Streptococcus pneumoniae. Although she was born after vacuum delivery and a scalp swelling was noticed from the third day of life, this swelling disappeared completely at the age of 3 months. Parents were thoroughly questioned but we could not find out a new traumatic head event. We postulate that in our patient, a subgaleal hemorrhage developed after vacuum delivery and possibly infected 11 months later, presumably from hematogenous seeding of an acute otitis media. The patient recovered well after surgical drainage and antimicrobial therapy.