Long-term outcomes of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities.

BACKGROUND: Microscopic evaluation of the entire surgical margin during excision of cutaneous malignancies results in the highest rates of complete excision and lowest rates of true local scar recurrence. Few studies demonstrate the outcomes of Mohs micrographic surgery specifically for invasive melanoma of the trunk and proximal portion of the extremities. OBJECTIVE: To evaluate the long-term efficacy of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities, including true local scar recurrence rate, distant recurrence-free survival, and disease-specific survival. METHODS: Prospectively collected study of 1416 cases of invasive melanoma of the trunk and proximal portion of the extremities was performed to evaluate long-term outcomes. RESULTS: True local scar recurrences occurred in our cohort at a rate of 0.14% (2/1416), after a mean follow-up period of 75 months and were not associated with tumor depth. The rate of satellite/in-transit recurrences and the disease-specific survival stratified by tumor thickness were superior to historical control values. LIMITATIONS: We used a nonrandomized, single institution, retrospective design. CONCLUSIONS: Mohs micrographic surgery of primary cutaneous invasive melanoma on the trunk and proximal portion of the extremities resulted in local control of 99.86% of tumors and an overall disease-specific death rate superior to that of wide local excision.

Lipophagic Panniculitis of Childhood: A Case Report and Comprehensive Review of the Literature.

Lipophagic panniculitis of childhood is a rare condition notable clinically for an inflammatory panniculitis followed by the development of permanent lipoatrophy. In this regard, the term lipoatrophic panniculitis has been used synonymously with lipophagic panniculitis. Additional designations include lipophagic lipoatrophic panniculitis and annular lipoatrophic panniculitis of the ankles. Although lipophagic panniculitis has been associated with a number of autoimmune phenomena, a paucity of reports and limited pathological analyses to date renders this disease an elusive one whose pathogenesis is not yet established. We describe the clinical, histopathologic, and immunohistochemical findings in a case of lipophagic panniculitis of childhood in a 7-year-old boy and present it in the context of a comprehensive review of the literature. Furthermore, we offer a hypothesis regarding the pathogenetic basis of lipophagic panniculitis of childhood, suggesting cellular immunity targeting the adipocyte at the crux of its pathogenesis.

Genome Modeling System: A Knowledge Management Platform for Genomics.

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

Photoprotection: part I. Photoprotection by naturally occurring, physical, and systemic agents.

The acute and chronic consequences of ultraviolet radiation on human skin are reviewed. An awareness of variations in naturally occurring photoprotective agents and the use of glass, sunglasses, and fabric can lead to effective protection from the deleterious effects of ultraviolet radiation. New systemic agents, including Polypodium leucotomos, afamelanotide, and antioxidants have potential as photoprotective agents.

Photoprotection: part II. Sunscreen: development, efficacy, and controversies.

In addition to the naturally occurring, physical, and systemic photoprotective agents reviewed in part I, topical ultraviolet radiation filters are an important cornerstone of photoprotection. Sunscreen development, efficacy, testing, and controversies are reviewed in part II of this continuing medical education article.

Quantitative analysis of approaches to measure cooperative phosphate release in polymerized actin.

We use stochastic simulations that treat several experimental probes of actin dynamics to explore the extent to which phosphate dissociation in filamentous actin may be cooperative. Phosphate time-courses from polymerization and copolymerization experiments of ATP- and ADP-actin are studied, including the effects of variations in filament-number concentration as well as single-filament depolymerization time-courses. We find that highly cooperative models are consistent with the treated experimental data. We also find that some types of experiments that are believed to provide strong constraints on the cooperativity of actin hydrolysis models do not provide such constraints.

Sunscreens: obtaining adequate photoprotection.

Adequate photoprotection plays a paramount role in reducing the burden of both photoaging and photocarcinogenesis. The scope of photoprotective strategies employed by the public, from most to least effective, includes: sun avoidance, seeking shade, the use of protective clothing, and the application of sunscreen. Among these options, sunscreen use remains the strategy most frequently employed by the public--a reversal of the preferred order of photoprotection. Given this trend, it is clear why sunscreens invariably take center stage in any discussion regarding obtaining adequate photoprotection.

Current sunscreen controversies: a critical review.

BACKGROUND/PURPOSE: Sunscreens are believed to be a valuable tool in providing photoprotection against the detrimental effects of UV radiation, a known carcinogen. However, a number of controversies have developed regarding their safety and efficacy. This review summarizes the relevant studies surrounding these controversies. METHODS: Evidence of the prevention of skin cancer, an oft-cited reason for sunscreen use, was examined as it pertains to squamous cell carcinoma, basal cell carcinoma and melanoma. We also reviewed studies examining the effects of sunscreen on the synthesis of vitamin D, an essential nutrient whose role in health and disease continues to grow. Lastly, we analyzed studies surrounding the safety and toxicity of oxybenzone, retinyl palmitate and nanoparticles of zinc oxide (ZnO) and titanium dioxide (TiO2 ). RESULTS: The overwhelming majority of available data is drawn from studies conducted using antiquated sunscreen formulations. Nonetheless, our research revealed that topical use of sunscreen protects against squamous cell carcinoma, does not cause vitamin D deficiency/insufficiency in practice and has not been demonstrated to adversely affect the health of humans. CONCLUSION: Given the established benefits of UV protection, the use of sunscreens remains an important part of an overall photoprotective strategy. Future sunscreens with improved formulation should ideally offer superior protection. With increased usage of sunscreen by the public, continuous and vigilant monitoring of the overall safety of future products is also needed.

Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling.

Superoxide dismutase 1 (SOD1) is an abundant copper/zinc enzyme found in the cytoplasm that converts superoxide into hydrogen peroxide and molecular oxygen. Tetrathiomolybdate (ATN-224) has been recently identified as an inhibitor of SOD1 that attenuates FGF-2- and VEGF-mediated phosphorylation of ERK1/2 in endothelial cells. However, the mechanism for this inhibition was not elucidated. Growth factor (GF) signaling elicits an increase in reactive oxygen species (ROS), which inactivates protein tyrosine phosphatases (PTP) by oxidizing an essential cysteine residue in the active site. ATN-224-mediated inhibition of SOD1 in tumor and endothelial cells prevents the formation of sufficiently high levels of H(2)O(2), resulting in the protection of PTPs from H(2)O(2)-mediated oxidation. This, in turn, leads to the inhibition of EGF-, IGF-1-, and FGF-2-mediated phosphorylation of ERK1/2. Pretreatment with exogenous H(2)O(2) or with the phosphatase inhibitor vanadate abrogates the inhibition of ERK1/2 phosphorylation induced by ATN-224 or SOD1 siRNA treatments. Furthermore, ATN-224-mediated SOD1 inhibition causes the down-regulation of the PDGF receptor. SOD1 inhibition also increases the steady-state levels of superoxide, which induces protein oxidation in A431 cells but, surprisingly, does not oxidize phosphatases. Thus, SOD1 inhibition in A431 tumor cells results in both prooxidant effects caused by the increase in the levels of superoxide and antioxidant effects caused by lowering the levels of H(2)O(2). These results identify SOD1 as a master regulator of GF signaling and as a therapeutic target for the inhibition of angiogenesis and tumor growth.

Cutaneous Leishmaniasis.

Leishmaniasis is a parasitic infection that can involve the skin, mucosal membranes, and internal organs. Soldiers are at highrisk of leishmaniasis when conducting operations in endemic regions. Medical providers should have a low threshold to consider Leishmaniasis as the cause of persisting skin lesions.

Centipede Bites.

The genus Scolopendra includes large centipedes that inhabit tropical regions of Southeast Asia and the Pacific Islands as well as South America and the Southwestern US. They are capable of inflicting a clinically significant venomous bite. These multilegged arthropods may enter tents or buildings at night in search of prey and tend to hide in bedding and clothing. Presentation and management are discussed.

Brucellosis.

Human brucellosis can be caused by different Brucella spp. When conducting operations in a country with high rates of brucellosis, extra precautions should be taken. Appropriate personal protective measures should be used in situations when close contact with animal carcasses cannot be avoided. Clinical diagnosis, treatment, and prevention are discussed.

Genome-wide association studies: a powerful tool for neurogenomics.

As their power and utility increase, genome-wide association (GWA) studies are poised to become an important element of the neurosurgeon's toolkit for diagnosing and treating disease. In this paper, the authors review recent findings and discuss issues associated with gathering and analyzing GWA data for the study of neurological diseases and disorders, including those of neurosurgical importance. Their goal is to provide neurosurgeons and other clinicians with a better understanding of the practical and theoretical issues associated with this line of research. A modern GWA study involves testing hundreds of thousands of genetic markers across an entire genome, often in thousands of individuals, for any significant association with a particular disease. The number of markers assayed in a study presents several practical and theoretical issues that must be considered when planning the study. Genome-wide association studies show great promise in our understanding of the genes underlying common neurological diseases and disorders, as well as in leading to a new generation of genetic tests for clinicians.

Scrub Typhus.

Scrub typhus, also known as tsutsugamushi disease, is caused by Orientia sp. and approximately 1 million new cases are reported annually. This article discusses the importance of scrub typhus and its clinical presentation, diagnosis, treatment, and prevention.

Measles (Rubeola): An Update.

Measles is a significant concern with approximately 10 million people infected annually causing over 100,000 deaths worldwide. In the US before use of the measles vaccine, there were estimated to be 3 to 4 million people infected with measles annually, causing 400 to 500 deaths. Complications of measles include otitis media, diarrhea, pneumonia, and acute encephalitis. Measles is a leading cause of blindness in the developing world, especially in those who are vitamin A deficient. Malnourished children with measles are also at higher risk of developing noma (or cancrum oris), a rapidly progressive gangrenous infection of the mouth and face. Most deaths due to measles are caused by pneumonia, diarrhea, or neurological complications in young children, severely malnourished or immunocompromised individuals, and pregnant women. A rare sequela of measles is subacute sclerosing panencephalitis.

Leptospirosis.

Leptospirosis is caused by an infection with bacteria of the Leptospira species. These spirochetes are carried by a variety of wild and domestic animals. Humans can become infected with these bacteria; leptospirosis most commonly occurs in the tropics and subtropics. Military personnel are at risk of infection through deployment in the field.

Use of complex fractionated atrial electrogram mapping system in mapping and ablating the atrial flutter of a transplanted heart.

Atrial flutter in donor part of orthotopic heart transplant has been reported and treated by radiofrequency ablation in the past. Complex fractionated atrial electrogram (CFE) mapping has been used to simplify the ablation of chronic atrial fibrillation. Here, we report a case with atrial flutter in an orthotopic heart transplant whose circuit mapping was difficult. Using CFE helped us to define the arrhythmia circuit easily and perform curative ablation.

Patients with depression who self-refer for transcranial magnetic stimulation treatment: exploratory qualitative study.

Aims and methodAs part of a larger clinical trial concerning the use of transcranial magnetic stimulation (TMS) for treatment-resistant depression, the current study aimed to examine referral emails to describe the clinical characteristics of people who self-refer and explore the reasons for self-referral for TMS treatment. We used content analysis to explore these characteristics and thematic analysis to explore the reasons for self-referral. RESULTS: Of the 98 referrals, 57 (58%) were for women. Depressive disorder was the most commonly cited diagnosis, followed by bipolar affective disorder. Six themes emerged from the thematic analysis: treatment resistance, side-effects of other treatments, desperation for relief, proactively seeking information, long-term illness and illness getting worse.Clinical implicationsTMS has recently been recommended in the UK for routine use in clinical practice. Therefore, the number of people who self-refer for TMS treatment is likely to increase as its availability increases.Declaration of interestNone.

Antibiotic resistance, molecular characterizations, and clinical manifestations of Campylobacteriosis at a military medical center in Hawaii from 2012-2016: a retrospective analysis.

Hawaii has one of the highest incidences of Campylobacteriosis in the United States, but there remains little published data on circulating strains or antimicrobial resistance. We characterized 110 clinical Campylobacter isolates (106 C. jejuni, 4 C. coli) processed at Tripler Army Medical Center in Honolulu, HI from 2012-2016. Twenty-five percent of C. jejuni isolates exhibited fluoroquinolone (FQ) resistance, compared with 16% for tetracycline (TET), and 0% for macrolides. Two of the four C. coli isolates were resistant to FQ, TET, and macrolides. C. jejuni isolates further underwent multilocus sequence typing, pulsed-field gel electrophoresis, and molecular capsular typing. Nineteen capsule types were observed, with two capsule types (HS2 and HS9) being associated with FQ resistance (p < 0.001 and p = 0.006, respectively). HS2 FQ-resistant isolates associated with clonal complex 21, possibly indicating clonal spread in FQ resistance. Macrolides should be considered for treatment of suspect cases due to lack of observed resistance.