We studied 24 patients with histologically verified cerebral cavernous malformations, reviewing the familial occurrence and presenting signs, symptoms, and radiographic features of the disorder. Eleven patients had no evidence of a heritable trait and had negative family histories. Thirteen patients were members of six unrelated Mexican-American families. Sixty-four first-degree and second-degree relatives were examined, and family pedigrees were established. Most relatives (83 percent) were asymptomatic; 11 percent had seizures. Magnetic resonance imaging was performed in 16 relatives (5 of whom were asymptomatic). Fourteen of the 16 studies revealed cavernous malformations; 11 studies identified multiple lesions. As compared with computerized tomography and angiography, magnetic resonance imaging was far more accurate in detecting cavernous malformations. We conclude that cavernous malformations are more prevalent than previously reported, and that a familial form of the disorder exists that is more common than expected, with a high incidence of multiple lesions and an increased frequency of occurrence among Mexican-American families. Magnetic resonance imaging is the radiographic technique of choice for the identification and follow-up of these lesions.

(89)Zr-anti-γH2AX-TAT allows PET imaging of DNA DSBs in a tumour xenograft mouse model.

Improved risk stratification and prognosis in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here three scientific groups were invited to independently generate prognostic models for 30-day mortality using 12 discovery cohorts (N=650) containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance was validated in 5 cohorts of community-onset sepsis patients (N=189) in which the models showed summary AUROCs ranging from 0.765-0.89. Similar performance was observed in 4 cohorts of hospital-acquired sepsis (N=282). Combining the new gene-expression-based prognostic models with prior clinical severity scores led to significant improvement in prediction of 30-day mortality (p<0.01). These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis, improving both resource allocation and prognostic enrichment in clinical trials.