Catastrophic cutaneous carcinomatosis in the non-organ transplant patient.

BACKGROUND: The increased frequency of nonmelanoma skin cancers (NMSCs) in organ transplant recipients has been termed "catastrophic cutaneous carcinomatosis" (CCC). We have treated a cohort of immunocompetent patients with an increased number of NMSCs that meets the definition of CCC whom we have termed "catastrophic cutaneous carcinomatosis-immunocompetent" (CCC-IC). OBJECTIVE: We sought to further understand the epidemiologic characteristics of this subset of immunocompetent patients with a high burden of NMSCs. METHODS: Our pathology database was searched over a 4-year experience of a Mohs surgeon to identify patients with greater than 10 basal cell carcinomas (BCCs) and/or squamous cell carcinomas (SCCs) in a 12-month period who had no underlying systemic cause of immunosuppression or genetic predisposition to form NMSCs. Information regarding the 13 patients who met inclusion criteria was collected by questionnaire and analyzed. RESULTS: There was no statistically significant difference in the constitutional variables of this patient population. Patients with CCC-IC had a SCC:BCC ratio of 2.5:1, similar to what is seen in organ transplant recipients where the SCC:BCC ratio is 2:1 with SCC predominance. There was a statistically significant increase in the number of SCCs in patients with CCC-IC (8.77/patient) as compared with control patients (2.27/patient). Most strikingly, a 13.8-fold higher incidence of malignant melanoma in the CCC-IC group was found as compared with the general population. LIMITATIONS: Limitations to this study include a small sample size and recall bias. CONCLUSION: Our data suggest that patients with CCC-IC have skin cancer profiles of SCC and BCC similar to organ transplant recipients and have a markedly higher incidence of malignant melanoma than the general population. These patients require strict monitoring and combination therapeutic approaches toward management of cutaneous carcinomas.

A randomized controlled trial of oral phosphate binders in the treatment of pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare connective tissue disorder involving fragmentation and mineralization of elastic fibers predominantly in the skin, eyes, and cardiovascular system. OBJECTIVE: The objective of this study was to assess the efficacy of sevelamer hydrochloride on the reversal of elastic fiber calcification and clinical lesions of PXE. METHODS: This was a randomized, double-blind, placebo-controlled, two-part prospective study. In the first year, 40 patients with PXE were randomized to receive either sevelamer hydrochloride (800 mg by mouth three times daily) or placebo in a 1:1 ratio. In the second year, all patients received sevelamer hydrochloride (800 mg by mouth three times daily). RESULTS: In the first year, the placebo and treatment groups' mean calcium scores decreased from 29.52 to 15.97 (41.93% mean improvement) and 27.48 to 16.75 (38.37% mean improvement), respectively. In the second year, the mean calcium scores decreased to 13.36 (53.94%) and 14.03 (51.35%) in these groups. The mean clinical score in the placebo group decreased from 6.25 to 6.05 at year 1 (2% improvement) whereas the mean clinical score in the sevelamer hydrochloride group decreased from 7.10 to 6.55 (7% improvement). In year 2, the scores in the original placebo and sevelamer hydrochloride groups decreased to 5.33 (14% improvement) and 5.72 (19% improvement), respectively. LIMITATIONS: Magnesium stearate in our placebo and active drugs may have played a confounding role in this study, contributing to the small differences observed in these two groups. CONCLUSION: Sevelamer hydrochloride produced a reduction in both calcification levels and clinical scores; however, this difference was not statistically significant compared with placebo. Future clinical studies should examine the inhibitory role and potential therapeutic effect of magnesium in PXE.

Use of high-frequency, high-resolution ultrasound before Mohs surgery.

BACKGROUND: Although ultrasound imaging is employed ubiquitously today, its use to examine and assess the skin is a relatively new technology. We explored the clinical application and use of high-frequency, high-resolution ultrasound in Mohs micrographic surgery. OBJECTIVE: To evaluate the ability of ultrasound to accurately determine lesion length and width of tumor borders in order to reduce the number of surgical stages. METHODS AND MATERIALS: This was an institutional review board-approved single-center study of 26 Mohs surgery patients. Ultrasound images were taken to record lesion dimensions, and then the investigator documented clinical estimation of the first stage. Extirpation of the tumor and histological analysis were performed thereafter. RESULTS: The results of 20 patients were included in the analysis. A paired-samples t-test revealed no significant difference between clinical and ultrasound widths (t=-1.324, p=.20). Similarly, there was no significant difference between the lengths found from clinical assessment and ultrasound (t=-1.093, p=.29). For different tumor types, there was no significant difference between clinical and ultrasound widths or lengths for basal cell carcinoma (t=-1.307, p=.23; t=-1.389, p=.20) or squamous cell cancer (t=-0.342, p=.73; t=0.427, p=.68). CONCLUSION There is a diagnostic role for high-resolution ultrasound in Mohs surgery regarding the delineation of surgical margins, but its limitations preclude its practical adoption at this time.

Utilization of a new tissue expander in the closure of a large Mohs surgical defect.

BACKGROUND: Malignant proliferating trichilemmal tumor (MPTT) is a rare neoplasm originating in the outer sheath of a hair follicle that often presents as a slowly enlarging, painful, subcutaneous scalp nodule. The authors describe a case of malignant proliferating trichilemmal tumor (MPTT) in an elderly 65-year-old Asian male who presented with a 5.5 x 5.0 cm mass on the posterior scalp. METHODS: The authors present a unique dual approach to treatment of MPTT in both the excision and wound revision phases. First, Mohs micrographic surgery is utilized for more discrete removal of malignant tissue, as opposed to wide excision. Then, a novel device called DermaClose RC is used in wound revision, a device that has proven to be more effective in promoting wound closure than traditional suturing. RESULTS: Mohs micrographic surgery was used to excise the tumor in three stages. The resulting irregular wound measured 6.3 x 5.6 cm, and was repaired with the device. Following the application of the device, the wound reduced in size to 1.5-1.0 cm. Postoperatively, the patient had no evidence of recurrent disease at seven months. CONCLUSION: Use of the DermaClose RC tissue expander following a Mohs surgical procedure provides an effective functional and cosmetic alternative to a skin graft which creates a donor site wound and creates a more complicated, time consuming procedure. The dual approach discussed here-of Mohs micrographic surgery performed in tandem with wound revision via the tissue expanding device is one that may yield promising benefits but warrants further evaluation.

Allergic contact dermatitis: patch testing results at Mount Sinai Medical Center.

Patch testing is an important diagnostic tool commonly used to identify allergens responsible for allergic contact dermatitis, especially in cases where the diagnosis is not clearly apparent. The authors report the patch test results from 2004-2008 and compare the results with the North American Contact Dermatitis Group and Mayo Clinic. Four hundred thirty-four patients with suspected allergic contact dermatitis underwent standardized patch testing with a tray consisting of 50 allergens at Mount Sinai Medical Center. Two hundred ninety patients (66.8%) had positive reactions to at least one allergen. The most frequent contact allergens included nickel sulfate (13%), fragrance mix (9.6%), propylene glycol (7.8%), neomycin sulfate (6.6%), thimerosal (6.4%), bacitracin (6.2%), and sodium gold thiosulfate (5.8%).

A five-patient satisfaction pilot study of calcium hydroxylapatite injection for treatment of aging hands.

BACKGROUND: The process of skin aging is not limited to the face but involves every part of the body, including the hands. A common manifestation of aging of the hands is the loss of volume, which occurs as the skin loses its subcutaneous fat. Injectable dermal fillers have surfaced as a popular method to address such deficiencies. OBJECTIVES: To report the use of calcium hydroxylapatite (CaHA) to address lost volume. METHODS: Five female subjects with soft tissue deficiency of the dorsa of the hands were enrolled at Mount Sinai Medical Center. A solution of CaHA with 2% lidocaine in amounts of 0.3 to 1.0 mL was injected interdigitally at each of three to five insertion sites; the sites were massaged and molded up to three times to ensure an optimal cosmetic end point. Subjects were seen for a follow-up visit after 1, 4, 16, and 24 weeks. RESULTS: With a single injection, all subjects reached their correction goals without requiring any touch-ups. At the 24-week visit, the subjects retained the filling effect, with no adverse events and high patient satisfaction. CONCLUSION: CaHA, a new, easily injectable, safe dermal filler, has emerged as an excellent option for soft tissue augmentation in aging hands.

Six-month safety results of calcium hydroxylapatite for treatment of nasolabial folds in Fitzpatrick skin types IV to VI.

BACKGROUND: Recently, the cosmetic market has seen an increase in the options for treatment for people with dark skin. OBJECTIVES: This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) in individuals with dark skin. METHODS: This open-label, nonrandomized, prospective, five-center trial enrolled 100 patients aged 18 and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25- to 27-gauge needle. Participants received a range of 0.6 to 2.8 mL of CaHA and returned at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. If necessary, each subject was offered a touch-up at the conclusion of the 6-month visit. RESULTS: No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events were recorded. CONCLUSIONS: People with dark skin injected subdermally with CaHA do not show signs of keloid formation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population.

Combined global localization analysis and transcriptome data identify genes that are directly coregulated by Adr1 and Cat8.

In Saccharomyces cerevisiae, glucose depletion causes a profound alteration in metabolism, mediated in part by global transcriptional changes. Many of the transcription factors that regulate these changes act combinatorially. We have analyzed combinatorial regulation by Adr1 and Cat8, two transcription factors that act during glucose depletion, by combining genome-wide expression and genome-wide binding data. We identified 32 genes that are directly activated by Adr1, 28 genes that are directly activated by Cat8, and 14 genes that are directly regulated by both. Our analysis also uncovered promoters that Adr1 binds but does not regulate and promoters that are indirectly regulated by Cat8, stressing the advantage of combining global expression and global localization analysis to find directly regulated targets. At most of the coregulated promoters, the in vivo binding of one factor is independent of the other, but Adr1 is required for optimal Cat8 binding at two promoters with a poor match to the Cat8 binding consensus. In addition, Cat8 is required for Adr1 binding at promoters where Adr1 is not required for transcription. These data provide a comprehensive analysis of the direct, indirect, and combinatorial requirements for these two global transcription factors.

Cost-benefit analysis of a hospital pharmacy bar code solution.

BACKGROUND: Bar coding can reduce hospital pharmacy dispensing errors, but it is unclear if the benefits of this technology justify its costs. The purpose of this study was to assess the costs and benefits and determine the return on investment at the institutional level for implementing a pharmacy bar code system. METHODS: We performed a cost-benefit analysis of a bar code-assisted medication-dispensing system within a large, academic, nonprofit tertiary care hospital pharmacy. We took the implementing hospital's perspective for a 5-year horizon. The primary outcome was the net financial cost and benefit after 5 years. The secondary outcome was the time until total benefits equaled total costs. Single-variable, 2-variable, and multiple-variable Monte Carlo sensitivity analyses were performed to test the stability of the outcomes. RESULTS: In inflation- and time value-adjusted 2005 dollars, total costs during 5 years were $2.24 million ($1.31 million in 1-time costs during the initial 3.5 years and $342 000 per year in recurring costs starting in year 3). The primary benefit was a decrease in adverse drug events from dispensing errors (517 events annually), resulting in an annual savings of $2.20 million. The net benefit after 5 years was $3.49 million. The break-even point for the hospital's investment occurred within 1 year after becoming fully operational. A net benefit was achieved within 10 years under almost all sensitivity scenarios. In the Monte Carlo simulation, the net benefit during 5 years was $3.2 million (95% confidence interval, -$1.2 million to $12.1 million), and the break-even point for return on investment occurred after 51 months (95% confidence interval, 30 to 180 months). CONCLUSION: Implementation of a bar code-assisted medication-dispensing system in hospital pharmacies can result in a positive financial return on investment for the health care organization.

Computational discovery of gene modules and regulatory networks.

We describe an algorithm for discovering regulatory networks of gene modules, GRAM (Genetic Regulatory Modules), that combines information from genome-wide location and expression data sets. A gene module is defined as a set of coexpressed genes to which the same set of transcription factors binds. Unlike previous approaches that relied primarily on functional information from expression data, the GRAM algorithm explicitly links genes to the factors that regulate them by incorporating DNA binding data, which provide direct physical evidence of regulatory interactions. We use the GRAM algorithm to describe a genome-wide regulatory network in Saccharomyces cerevisiae using binding information for 106 transcription factors profiled in rich medium conditions data from over 500 expression experiments. We also present a genome-wide location analysis data set for regulators in yeast cells treated with rapamycin, and use the GRAM algorithm to provide biological insights into this regulatory network

Black dot tinea capitis in an immunosuppressed man.

Tinea capitis is a common superficial fungal infection of the scalp primarily afflicting young children. In adults, this infection may have an atypical presentation that may lead to a delay in diagnosis. The authors present a case report of black dot tinea capitis in an immunosuppressed Asian man with psoriasis and provide a review of the literature.