Integrating transcriptomic sequencing with conventional cytogenetics, we identified WWTR1 (WW domain-containing transcription regulator 1) (3q25) and CAMTA1 (calmodulin-binding transcription activator 1) (1p36) as the two genes involved in the t(1;3)(p36;q25) chromosomal translocation that is characteristic of epithelioid hemangioendothelioma (EHE), a vascular sarcoma. This WWTR1/CAMTA1 gene fusion is under the transcriptional control of the WWTR1 promoter and encodes a putative chimeric transcription factor that joins the amino terminus of WWTR1, a protein that is highly expressed in endothelial cells, in-frame to the carboxyl terminus of CAMTA1, a protein that is normally expressed only in brain. Thus, CAMTA1 expression is activated inappropriately through a promoter-switch mechanism. The gene fusion is present in virtually all EHEs tested but is absent from all other vascular neoplasms, demonstrating it to be a disease-defining genetic alteration. A sensitive and specific break-apart fluorescence in situ hybridization assay was also developed to detect the translocation and will assist in the evaluation of this diagnostically challenging neoplasm. The chimeric WWTR1/CAMTA1 transcription factor may represent a therapeutic target for EHE and offers the opportunity to shed light on the functions of two poorly characterized proteins.

The human gastrointestinal tract is home to hundreds of species of bacteria and the balance between beneficial and pathogenic bacteria plays a critical role in human health and disease. The human infant, however, is born with a sterile gut and the complex gastrointestinal host/bacterial ecosystem is only established after birth by rapid bacterial colonization. Composition of newborn gut flora depends on several factors including type of birth (Ceasarian or natural), manner of early feeding (breast milk or formula), and exposure to local, physical environment. Imbalance in normal, healthy gut flora contributes to several adult human diseases including inflammatory bowel (ulcerative colitis and Crohn's disease) and Clostridium difficile associated disease, and early childhood diseases such as necrotizing enterocolitis. As a first step towards characterization of the role of gut bacteria in human health and disease, we conducted an 850 MHz (1)H nuclear magnetic resonance spectroscopy study to monitor changes in metabolic profiles of urine and fecal extracts of 15 mice following gut sterilization by the broad-spectrum antibiotic enrofloxacin (also known as Baytril). Ten metabolites changed in urine following enrofloxacin treatment including decreased acetate due to loss of microbial catabolism of sugars and polysaccharides, decreased trimethylamine-N-oxide due to loss of microbial catabolism of choline, and increased creatine and creatinine due to loss of microbial enzyme degradation. Eight metabolites changed in fecal extracts of mice treated with enrofloxacin including depletion of amino acids produced by microbial proteases, reduction in metabolites generated by lactate-utilizing bacteria, and increased urea caused by loss of microbial ureases.

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BackgroundDespite advances in surgical techniques, sterile protocols, and perioperative antibiotic regimens, surgical site infections (SSIs) remain a significant problem. We investigated the relationship between wound classification (i.e., clean, clean/contaminated, contaminated, dirty) and SSI rates in plastic surgery.MethodsWe performed a retrospective review of a multi-institutional, surgical outcomes database for all patients undergoing plastic surgery procedures from 2006-2010. Patient demographics, wound classification, and 30-day outcomes were recorded and analyzed by multivariate logistic regression.ResultsA total of 15,289 plastic surgery cases were analyzed. The overall SSI rate was 3.00%, with superficial SSIs occurring at comparable rates across wound classes. There were similar rates of deep SSIs in the clean and clean/contaminated groups (0.64%), while rates reached over 2% in contaminated and dirty cases. Organ/space SSIs occurred in less than 1% of each wound classification. Contaminated and dirty cases were at an increased risk for deep SSIs (odds ratios, 2.81 and 2.74, respectively); however, wound classification did not appear to be a significant predictor of superficial or organ/space SSIs. Clean/contaminated, contaminated, and dirty cases were at increased risk for a postoperative complication, and contaminated and dirty cases also had higher odds of reoperation and 30-day mortality.ConclusionsAnalyzing a multi-center database, we found that wound classification was a significant predictor of overall complications, reoperation, and mortality, but not an adequate predictor of surgical site infections. When comparing infections for a given wound classification, plastic surgery had lower overall rates than the surgical population at large.