A Protease-Activated Fluorescent Probe Allows Rapid Visualization of Keratinocyte Carcinoma during Excision.

Keratinocyte carcinomas, including basal and squamous cell carcinomas, are the most common human cancers worldwide. While 75% of all keratinocyte carcinoma (4 million annual cases in the United States) are treated with conventional excision, this surgical modality has much lower cure rates than Mohs micrographic surgery, likely due to the bread-loaf histopathologic assessment that visualizes <1% of the tissue margins. A quenched protease-activated fluorescent probe 6qcNIR, which produces a signal only in the protease-rich tumor microenvironment, was topically applied to 90 specimens ex vivo immediately following excision. "Puzzle-fit" analysis was used to correlate the fluorescent images with histology. Probe-dependent fluorescent images correlated with cancer determined by conventional histology. Point-of-care fluorescent detection of skin cancer had a clinically relevant sensitivity of 0.73 and corresponding specificity of 0.88. Importantly, clinicians were effectively trained to read fluorescent images within 15 minutes with reliability and confidence, resulting in sensitivities of 62%-78% and specificities of 92%-97%. Fluorescent imaging using 6qcNIR allows 100% tumor margin assessment by generating en face images that correlate with histology and may be used to overcome the limitations of conventional bread-loaf histology. The utility of 6qcNIR was validated in a busy real-world clinical setting, and clinicians were trained to effectively read fluorescent margins with a short guided instruction, highlighting clinical adaptability. When used in conventional excision, this approach may result in higher cure rates at a lower cost by allowing same-day reexcision when needed, reducing patient anxiety and improving compliance by expediting postsurgical specimen assessment. SIGNIFICANCE: A fluorescent-probe-tumor-visualization platform was developed and validated in human keratinocyte carcinoma excision specimens that may provide simple, rapid, and global assessment of margins during skin cancer excision, allowing same-day reexcision when needed.

An expert panel consensus on opioid-prescribing guidelines for dermatologic procedures.

BACKGROUND: Opioid overprescribing is a major contributor to the opioid crisis. The lack of procedure-specific guidelines contributes to the vast differences in prescribing practices. OBJECTIVE: To create opioid-prescribing consensus guidelines for common dermatologic procedures. METHODS: We used a 4-step modified Delphi method to conduct a systematic discussion among a panel of dermatologists in the fields of general dermatology, dermatologic surgery, and cosmetics/phlebology to develop opioid prescribing guidelines for some of the most common dermatologic procedural scenarios. Guidelines were developed for opioid-naive patients undergoing routine procedures. Opioid tablets were defined as oxycodone 5-mg oral equivalents. RESULTS: Postoperative pain after most uncomplicated procedures (76%) can be adequately managed with acetaminophen and/or ibuprofen. Group consensus identified no specific dermatologic scenario that routinely requires more than 15 oxycodone 5-mg oral equivalents to manage postoperative pain. Group consensus found that 23% of the procedural scenarios routinely require 1 to 10 opioid tablets, and only 1 routinely requires 1 to 15 opioid tablets. LIMITATIONS: These recommendations are based on expert consensus in lieu of quality evidence-based outcomes research. These recommendations must be individualized to accommodate patients' comorbidities. CONCLUSIONS: Procedure-specific opioid prescribing guidelines may serve as a foundation to produce effective and responsible postoperative pain management strategies after dermatologic interventions.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

Improper Potency and Impurities in Compounded Polidocanol

Polidocanol is an FDA-approved sclerosant indicated for treating uncomplicated spider veins and reticular veins in the lower extremities. Despite restrictions against compounding drugs that are essentially copies of FDA-approved or commercially available products, polidocanol is also available from compounding pharmacies and outsourcing facilites. Compounded drug products are not FDA-approved and have not undergone premarket FDA review for safety, effectiveness, and quality. Seven samples of polidocanol were obtained from three compounding pharmacies and analyzed using high pressure liquid chromatography. None of the samples contained the labeled concentration of polidocanol and five contained excessive levels of impurities. Since the potency and purity of compounded polidocanol injection cannot be assured, physicians who use these products should consider FDA-approved products to ensure optimal safety and efficacy. J Drugs Dermatol. 2019;18(11):1124-1127.

Significant physician practice variability in the utilization of endovenous thermal ablation in the 2017 Medicare population.

BACKGROUND: There has been a substantial increase in the use of procedures to treat lower extremity venous disease in the United States over the past decade. A specialty society-selected metric was applied to evaluate the use of endovenous thermal ablation (EVTA) in Medicare beneficiaries and factors associated with physician practice variations. We used confidential physician reports of this benchmark data to increase physician recognition of individualized usage relative to their peers. METHODS: We used 100% Medicare fee-for-service claims data to identify all patients 18 years of age and older who underwent at least one lower extremity EVTA over a 1-year period (January 1, 2017, to December 31, 2017). A physician-specific annual rate of EVTA performed per patient was calculated. Individual physician results were shared confidentially with each provider billing Medicare for more than 10 ablations during the study period by mail, benchmarked to the distribution of use by their peers nationally. Hierarchical multivariable linear regression was used to identify patient and provider characteristics associated with high rates of thermal ablations per patient. RESULTS: A total of 102,145 Medicare beneficiaries (median age, 72.1 years; 67.8% female) underwent an EVTA by 2462 physicians during the study period. The majority (96.4%) of patients underwent 1 to 5 ablations, 3.3% underwent 6 to 10 ablations, and 0.3% underwent 11 or more ablations. The median and mean physician ablation rates were 1.6 (interquartile range, 1.3-2.2) and 1.9 ± 0.8 ablations per patient annually, respectively. There were 106 physicians (4.3%) who had an ablation rate of 3.4 or greater, which is two or more standard deviations above the national mean. After adjusting for patient-level variables, characteristics independently associated with outlier physicians included specialties other than vascular surgery, fewer years in practice, and higher overall venous ablation practice volume (P ≤ .03). CONCLUSIONS: Using a physician-generated metric of performance, the physician use EVTA performed annually per patient is highly variable, and this variability correlated with physician discipline, years in practice, and is more common in physicians who perform ablation the most. Our data show that there is considerable variability in the use of EVTA in Medicare beneficiaries, and that outlier physicians performing a high number of venous ablation procedures per patient are identifiable using a peer-benchmarked practice pattern measure via claims-based data.

Evidence-Based Clinical Practice Guidelines for Microcystic Adnexal Carcinoma: Informed by a Systematic Review.

IMPORTANCE: Microcystic adnexal carcinoma (MAC) occurs primarily in older adults of white race/ethnicity on sun-exposed skin of the head and neck. There are no formal guiding principles based on expert review of the evidence to assist clinicians in providing the highest-quality care for patients. OBJECTIVE: To develop recommendations for the care of adults with MAC. EVIDENCE REVIEW: A systematic review of the literature (1990 to June 2018) was performed using MEDLINE, Embase, Web of Science, and the Cochrane Library. The keywords searched were microcystic adnexal carcinoma, sclerosing sweat gland carcinoma, sclerosing sweat duct carcinoma, syringomatous carcinoma, malignant syringoma, sweat gland carcinoma with syringomatous features, locally aggressive adnexal carcinoma, and combined adnexal tumor. A multidisciplinary expert committee critically evaluated the literature to create recommendations for clinical practice. Statistical analysis was used to estimate optimal surgical margins. FINDINGS: In total, 55 studies met our inclusion criteria. The mean age of 1968 patients across the studies was 61.8 years; 54.1% were women. Recommendations were generated for diagnosis, treatment, and follow-up of MAC. There are 5 key findings of the expert committee based on the available evidence: (1) A suspect skin lesion requires a deep biopsy that includes subcutis. (2) MAC confined to the skin is best treated by surgery that examines the surrounding and deep edges of the tissue removed (Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment). (3) Radiotherapy can be considered as an adjuvant for MAC at high risk for recurrence, surgically unresectable tumors, or patients who cannot have surgery for medical reasons. (4) Patients should be seen by a physician familiar with MAC every 6 to 12 months for the first 5 years after treatment. Patient education on photoprotection, periodic skin self-examination, postoperative healing, and the possible normal changes in local sensation (eg, initial hyperalgesia) should be considered. (5) There is limited evidence to guide the treatment of metastasis in MAC due to its rarity. Limitations of our findings are that the medical literature on MAC comprises only retrospective reviews and descriptions of individual patients and there are no controlled studies to guide management. CONCLUSIONS AND RELEVANCE: The presented clinical practice guidelines provide an outline for the diagnosis and management of MAC. Future efforts using multi-institutional registries may improve our understanding of the natural history of the disease in patients with lymph node or nerve involvement, the role of radiotherapy, and the treatment of metastatic MAC with drug therapy.

The use of 3-dimensionally printed models to optimize patient education and alleviate perioperative anxiety in Mohs micrographic surgery: A randomized controlled trial.

BACKGROUND: Perioperative patient anxiety in Mohs micrographic surgery (MMS) is associated with increased postoperative pain and decreased satisfaction. OBJECTIVE: To determine whether a 3-dimensionally printed MMS model with standardized education (SE) improves perioperative patient understanding and anxiety. METHODS: An unblinded, randomized controlled trial was conducted, with patients randomly assigned to receive the MMS model plus SE or SE alone. Baseline and poststage understanding and anxiety were evaluated with the Visual Analog Scale (VAS) and State-Trait Anxiety Inventory (STAI). Additionally, patients completed a 6-item knowledge assessment. RESULTS: Eighty-two patients were enrolled, 42 in the MMS model and 40 in the SE group, with similar group mean age (67.8 years), sex (59.8% male), and previous MMS experience (47.6%). Both groups experienced significant reductions in VAS anxiety and State-Trait Anxiety Inventory scores and significant increases in VAS understanding. Compared with SE alone, the MMS model group had larger VAS anxiety reduction (change, -1.31; approaching significance) than the SE group (change, -0.52; P = .052) and 5.59 (93.25%) correct responses versus 5.15 (85.83%) correct responses in the SE group (P < .028). LIMITATIONS: Overestimations of baseline patient anxiety in our population and 91.1% recruitment of the intended study population limited study power. CONCLUSION: A 3-dimensionally printed MMS model with SE may improve patient understanding of MMS and decrease perioperative anxiety.

Characterization of the facial microbiome in twins discordant for rosacea.

Previously, we determined that genetic and environmental factors contributed equally towards rosacea in twins. To assess an environmental factor, we characterized the malar cheek bacterial microbiome from twins discordant for rosacea. We found no significant difference in facial microbiome alpha and beta diversity between related twins discordant for rosacea. However, the relative percentage abundance of Gordonia and Geobacillus, low-abundant genera, was positively and negatively associated with rosacea severity, respectively. Our data demonstrate a significant correlation between facial microbiome and severity of rosacea in genetically matched twins and importantly that overall microbiome composition is largely unchanged.

Rapid visualization of nonmelanoma skin cancer.

BACKGROUND: Mohs micrographic surgery examines all margins of the resected sample and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not readily amenable to Mohs micrographic surgery. This defines an unmet clinical need to assess the completeness of non-Mohs micrographic surgery resections during surgery to prevent re-excision/recurrence. OBJECTIVE: We sought to examine the utility of quenched activity-based probe imaging to discriminate cancerous versus normal-appearing skin tissue. METHODS: The quenched activity-based probe GB119 was applied to NMSC excised from 68 patients. We validated activation of the probe for hematoxylin-eosin-confirmed cancerous tissue versus normal-appearing skin tissue. RESULTS: Topical application of the probe differentiated basal cell carcinoma and squamous cell carcinoma from normal-appearing skin with overall estimated sensitivity and specificity of 0.989 (95% confidence interval 0.940-1.00) and 0.894 (95% confidence interval 0.769-0.965), respectively. Probe activation accurately defined peripheral margins of NMSC as compared with conventional hematoxylin-eosin-based pathology. LIMITATIONS: This study only examined NMSC debulking excision specimens. The sensitivity and specificity for this approach using final NMSC excision margins will be clinically important. CONCLUSIONS: These findings merit further studies to determine whether quenched activity-based probe technology may enable cost-effective increased cure rates for patients with NMSC by reducing re-excision and recurrence rates with a rapid and easily interpretable technological advance.

Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based Survey of Twins.

IMPORTANCE: To our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions. OBJECTIVES: To study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility. DESIGN, SETTING, AND PARTICIPANTS: Identical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated. MAIN OUTCOMES AND MEASURES: The NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists. RESULTS: Among the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins (r = 0.69 vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age (r = 0.38; P < .001) and lifetime UV radiation exposure (r = 0.26; P < .001). These associations remained after use of propensity score matching to adjust for multicollinearity. Other correlated variables included body mass index (r = 0.21; P < .001), smoking (r = 0.10; P < .02), alcohol consumption (r = 0.11; P = .01), cardiovascular comorbidity (r = 0.17; P < .001), and skin cancer comorbidity (r = 0.19; P < .001). CONCLUSIONS AND RELEVANCE: The study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.

Role of lymphocytic choriomeningitis virus (LCMV) in understanding viral immunology: past, present and future.

Lymphocytic choriomeningitis virus (LCMV) is a common infection of rodents first identified over eighty years ago in St. Louis, MO, U.S.A. It is best known for its application in immunological studies. The history of LCMV closely correlates with the development of modern immunology. With the use of LCMV as a model pathogen several key concepts have emerged: Major Histocompatibility Complex (MHC) restriction, T cell memory, persistent infections, T cell exhaustion and the key role of immune pathology in disease. Given the phenomenal infrastructure within this field (e.g., defined immunodominant and subdominant epitopes to all T cell receptor specificities as well as the cognate tetramers for enumeration in vivo) the study of LCMV remains an active and productive platform for biological research across the globe to this day. Here we present a historical primer that highlights several breakthroughs since the discovery of LCMV. Next, we highlight current research in the field and conclude with our predictions for future directions in the remarkable field of LCMV research.

Sclerotherapy: it is back and better.

With the recent US Food and Drug Administration (FDA) approval of polidocanol in the United States, there has been a resurgence of interest in sclerotherapy. Despite the popularity of laser therapy, sclerotherapy remains the gold standard for treating spider and reticular veins. Although this traditional method of treatment has been around for more than 100 years, better sclerosing agents and newer techniques have made sclerotherapy safer and more efficacious than ever before. This article is a primer for physicians interested in updating their skills in sclerotherapy. It reviews common sclerosants, sclerotherapy techniques, patient evaluation, complications, and recent advancements in sclerotherapy.

Life cycle environmental impacts of selected U.S. ethanol production and use pathways in 2022.

Projected life cycle greenhouse gas (GHG) emissions and net energy value (NEV) of high-ethanol blend fuel (E85) used to propel a passenger car in the United States are evaluated using attributional life cycle assessment. Input data represent national-average conditions projected to 2022 for ethanol produced from corn grain, corn stover, wheat straw, switchgrass, and forest residues. Three conversion technologies are assessed: advanced dry mill (corn grain), biochemical (switchgrass, corn stover, wheat straw), and thermochemical (forest residues). A reference case is compared against results from Monte Carlo uncertainty analysis. For this case, one kilometer traveled on E85 from the feedstock-to-ethanol pathways evaluated has 43%-57% lower GHG emissions than a car operated on conventional U.S. gasoline (base year 2005). Differences in NEV cluster by conversion technology rather than by feedstock. The reference case estimates of GHG and NEV skew to the tails of the estimated frequency distributions. Though not as optimistic as the reference case, the projected median GHG and NEV for all feedstock-to-E85 pathways evaluated offer significant improvement over conventional U.S. gasoline. Sensitivity analysis suggests that inputs to the feedstock production phase are the most influential parameters for GHG and NEV. Results from this study can be used to help focus research and development efforts.

Chemowraps as an adjuvant to surgery for patients with diffuse squamous cell carcinoma of the extremities.

BACKGROUND: Managing patients with diffuse squamous cell carcinoma (SCC) and actinic damage on their extremities is challenging because SCCs may be ill-defined, confluent, and only amenable to radical surgery. Diffuse actinic keratoses put patients at risk for further malignancies and may be difficult to distinguish from SCCs. An experience using chemowraps, a novel approach involving weekly 5-fluorouracil (5-FU) 5% cream under Unna wraps to reduce actinic keratoses, as an adjuvant to surgery is described. METHODS: A series of 3 representative patients is presented. Before chemowraps were applied, biopsies and clinical lymph node examinations were performed to confirm the diagnosis of SCC. Patients were informed that chemowraps represent an off-label use of 5-FU to reduce actinic keratoses as an adjuvant to definitive surgery for SCCs. RESULTS: Three patients were referred for diffuse actinic damage and biopsy-proven SCCs on the legs. Patients tolerated chemowraps well (applied for 4-20 weeks) and showed reduction in clinical lesions at 6 weeks to 3 years follow-up. CONCLUSIONS: Chemowraps may be useful in managing patients with diffuse SCCs in fields of severe actinic damage on the extremities. As an adjuvant to surgery, chemowraps may treat surrounding actinic keratoses, help define tumor borders, and minimize the extent of surgery required.

New advances in liposuction technology.

Although suction-assisted liposuction under tumescent anesthesia remains the traditional method for body sculpting, newer technologies promise to increase efficiency, decrease surgeon fatigue, and minimize complication. Power-, ultrasound-, and laser-assisted devices are ideal in large volume cases and in areas of fibrous tissues as an adjunct to traditional liposuction. Although skepticism remains chemical lipolysis, more commonly termed mesotherapy or lipodissolve may be an alternative to surgical treatment of localized fat. This article reviews the recent advancements in the field of liposuction and the current literature which support their use.