Verruciform xanthoma in recessive dystrophic epidermolysis bullosa and keratitis-ichthyosis-deafness syndrome: Report of two cases and a review of the literature.

Verruciform xanthoma is a benign, wart-like lesion that can clinically mimic squamous cell carcinoma. We describe two teenage patients with severe genodermatoses, recessive dystrophic epidermolysis bullosa (RDEB), and keratitis-ichthyosis-deafness (KID) syndrome, respectively, each found to have plaques suspicious for malignancy, later demonstrated on histopathologic examination to be verruciform xanthoma. We discuss the connection between these severe genodermatoses and the suspected pathophysiology of verruciform xanthoma. In addition, we highlight the importance of recognizing verruciform xanthoma as a clinical mimicker of squamous cell carcinoma, for which patients with RDEB and KID syndrome are at increased risk.

Wireless Pressure Ulcer Sensor: Validation in an Animal Model.

Pressure ulcers are increasingly prevalent in an aging population. The most commonly used method of pressure ulcer prevention is pressure off-loading achieved by physically turning bedbound patients or by using expensive, single application devices such as wheelchair cushions. Our aim is to approach the problem of pressure ulcer prevention in a new way: a wireless sensor worn by the patient at locations susceptible to pressure injury. The sensor will monitor local pressure over time and transmits the data wirelessly to a base station (in a hospital setting) or smartphone (for home care). When a condition that would be harmful to tissue is reached, an alert would enable immediate direct intervention to prevent development of a pressure ulcer. The goal of this study was to validate the sensor's use in a live animal model and to lay the foundation for building time-pressure curves to predict the probability of pressure injury. Sprague-Dawley rats underwent surgical implantation of bilateral steel discs deep to the latissimus dorsi muscles. After the animals recovered from the surgical procedure, pressure was applied to the overlying tissue using magnets of varying strengths (30-150 mm Hg) for between 1 and 8 hours. Our sensor was placed on the skin prior to magnet application to wirelessly collect data regarding pressure and time. Three days after pressure application, animals were killed, injuries were graded clinically, and biopsies were collected for histological analysis. Results reveal that all animals with magnet application for more than 2 hours had clinical evidence of ulceration. Similarly, histological findings of hemorrhage were associated with increased time of pressure application. However, at high pressures (120-150 mm Hg), there were ischemic changes within the muscular layer without corresponding skin ulceration. We have developed a wireless sensor that can be placed on any at-risk area of the body and has the potential to alert caregivers when patients are at risk of developing a pressure injury. Our sensor successfully transmitted pressure readings wirelessly in a live, mobile animal. Future studies will focus on safety and efficacy with human use and development of algorithms to predict the probability of pressure ulcer formation.

Apurinic/apyrimidinic endonuclease 2 is necessary for normal B cell development and recovery of lymphoid progenitors after chemotherapeutic challenge.

B cell development involves rapid cellular proliferation, gene rearrangements, selection, and differentiation, and it provides a powerful model to study DNA repair processes in vivo. Analysis of the contribution of the base excision repair pathway in lymphocyte development has been lacking primarily owing to the essential nature of this repair pathway. However, mice deficient for the base excision repair enzyme, apurinic/apyrimidinic endonuclease 2 (APE2) protein develop relatively normally, but they display defects in lymphopoiesis. In this study, we present an extensive analysis of bone marrow hematopoiesis in mice nullizygous for APE2 and find an inhibition of the pro-B to pre-B cell transition. We find that APE2 is not required for V(D)J recombination and that the turnover rate of APE2-deficient progenitor B cells is nearly normal. However, the production rate of pro- and pre-B cells is reduced due to a p53-dependent DNA damage response. FACS-purified progenitors from APE2-deficient mice differentiate normally in response to IL-7 in in vitro stromal cell cocultures, but pro-B cells show defective expansion. Interestingly, APE2-deficient mice show a delay in recovery of B lymphocyte progenitors following bone marrow depletion by 5-fluorouracil, with the pro-B and pre-B cell pools still markedly decreased 2 wk after a single treatment. Our data demonstrate that APE2 has an important role in providing protection from DNA damage during lymphoid development, which is independent from its ubiquitous and essential homolog APE1.