Code Crimson: A Postpartum Hemorrhage Bundled Intervention Quality Improvement Project.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternity mortality in the United States. The Code Crimson project aimed to enhance PPH management by implementing a standardized intervention bundle to mitigate morbidity and mortality associated with PPH. LOCAL PROBLEM: At a large Philadelphia tertiary hospital, health disparities existed for severe maternal morbidity and mortality, and PPH was a significant factor. METHODS: A quality improvement design, using Plan-Do-Study-Act cycles and interrupted time series analysis, was undertaken. INTERVENTIONS: The Code Crimson project implemented a standardized bundle to manage PPH, including blood product administration and massive transfusion protocol activation. RESULTS: After implementing the Code Crimson bundle, there was a significant decrease in blood product use ( P < .001), with minor reductions in packed red blood cell administration over 4 units and mean blood loss. CONCLUSIONS: The Code Crimson bundle effectively reduced blood product utilization for PPH treatment.

GnRH Induces Citrullination of the Cytoskeleton in Murine Gonadotrope Cells.

Peptidylarginine deiminases (PADs or PADIs) catalyze the conversion of positively charged arginine to neutral citrulline, which alters target protein structure and function. Our previous work established that gonadotropin-releasing hormone agonist (GnRHa) stimulates PAD2-catalyzed histone citrullination to epigenetically regulate gonadotropin gene expression in the gonadotrope-derived LßT2 cell line. However, PADs are also found in the cytoplasm. Given this, we used mass spectrometry (MS) to identify additional non-histone proteins that are citrullinated following GnRHa stimulation and characterized the temporal dynamics of this modification. Our results show that actin and tubulin are citrullinated, which led us to hypothesize that GnRHa might induce their citrullination to modulate cytoskeletal dynamics and architecture. The data show that 10 nM GnRHa induces the citrullination of ß-actin, with elevated levels occurring at 10 min. The level of ß-actin citrullination is reduced in the presence of the pan-PAD inhibitor biphenyl-benzimidazole-Cl-amidine (BB-ClA), which also prevents GnRHa-induced actin reorganization in dispersed murine gonadotrope cells. GnRHa induces the citrullination of ß-tubulin, with elevated levels occurring at 30 min, and this response is attenuated in the presence of PAD inhibition. To examine the functional consequence of ß-tubulin citrullination, we utilized fluorescently tagged end binding protein 1 (EB1-GFP) to track the growing plus end of microtubules (MT) in real time in transfected LßT2 cells. Time-lapse confocal microscopy of EB1-GFP reveals that the MT average lifetime increases following 30 min of GnRHa treatment, but this increase is attenuated by PAD inhibition. Taken together, our data suggest that GnRHa-induced citrullination alters actin reorganization and MT lifetime in gonadotrope cells.

Pruritus related to trastuzumab and pertuzumab in HER2 + breast cancer patients.

PURPOSE: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2 + breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. METHODS: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2 + breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. RESULTS: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. CONCLUSIONS: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

Prospective validation of dermoscopy-based open-source artificial intelligence for melanoma diagnosis (PROVE-AI study).

The use of artificial intelligence (AI) has the potential to improve the assessment of lesions suspicious of melanoma, but few clinical studies have been conducted. We validated the accuracy of an open-source, non-commercial AI algorithm for melanoma diagnosis and assessed its potential impact on dermatologist decision-making. We conducted a prospective, observational clinical study to assess the diagnostic accuracy of the AI algorithm (ADAE) in predicting melanoma from dermoscopy skin lesion images. The primary aim was to assess the reliability of ADAE's sensitivity at a predefined threshold of 95%. Patients who had consented for a skin biopsy to exclude melanoma were eligible. Dermatologists also estimated the probability of melanoma and indicated management choices before and after real-time exposure to ADAE scores. All lesions underwent biopsy. Four hundred thirty-five participants were enrolled and contributed 603 lesions (95 melanomas). Participants had a mean age of 59 years, 54% were female, and 96% were White individuals. At the predetermined 95% sensitivity threshold, ADAE had a sensitivity of 96.8% (95% CI: 91.1-98.9%) and specificity of 37.4% (95% CI: 33.3-41.7%). The dermatologists' ability to assess melanoma risk significantly improved after ADAE exposure (AUC 0.7798 vs. 0.8161, p = 0.042). Post-ADAE dermatologist decisions also had equivalent or higher net benefit compared to biopsying all lesions. We validated the accuracy of an open-source melanoma AI algorithm and showed its theoretical potential for improving dermatology experts' ability to evaluate lesions suspicious of melanoma. Larger randomized trials are needed to fully evaluate the potential of adopting this AI algorithm into clinical workflows.

Management of immune-related cutaneous adverse events with dupilumab.

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70-90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.

Pruritus Related to Trastuzumab and Pertuzumab in HER2+ Breast Cancer Patients.

Purpose: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2+ breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. Methods: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2+ breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. Results: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. Conclusions: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

An evaluation of implementation climate in inpatient maternity care: a cross-sectional survey study.

OBJECTIVE: Researchers in obstetrics and gynecology are continuously generating new evidence to inform clinical care delivery. Yet, much of this newly emerging evidence fails to be rapidly and effectively integrated into routine clinical practice. Implementation climate refers to clinicians' perceptions of to what degree organizations support and reward use of an evidence-based practice (EBP) and is an important construct in the science of implementation in healthcare. Little is known about implementation climate for EBPs in maternity care. Thus, we aimed to (a) determine the reliability of the Implementation Climate Scale (ICS) for use in inpatient maternity care, (b) describe implementation climate in inpatient maternity care overall, and (c) compare individual perceptions of implementation climate between physician and nursing clinicians on these units. STUDY DESIGN: We performed a cross-sectional survey of clinicians in inpatient maternity units across 2 urban, academic hospitals in the northeastern United States in 2020. Clinicians completed the 18-question validated ICS [scored 0-4]. Scale reliability by role was evaluated using Cronbach's α. Subscale and total scores were described overall and compared by physician versus nursing role using independent t-tests, as well as linear regression to control for confounders. RESULTS: 111 clinicians completed the survey (physicians = 65; nursing = 46). Physicians were less likely to identify as female (75.4% vs. 100.0%, p < .001), but were of similar age and years of experience as nursing clinicians. Reliability of the ICS was excellent, with Cronbach's α of 0.91 and 0.86 among physicians and nursing clinicians, respectively. Scores were notably low for implementation climate in maternity care overall and for all subscales. ICS total scores were also higher among physicians as compared to nurses (2.18(±0.56) vs. 1.92(±0.50), p = .02), which remained significant in multivariable modeling (p = .02). Unadjusted subscale scores were higher among physicians in Recognition for EBP (2.68(±0.89) vs. 2.30(±0.86), p = .03) and Selection for EBP (2.24(±0.93) vs. 1.62(±1.04), p = .002). After adjustment for potential confounders, subscale scores for Focus on EBP (p = .04) and Selection for EBP (p = .002) were all higher among physicians. CONCLUSIONS: This study supports the ICS as a reliable scale for measuring implementation climate in the inpatient maternity care setting. Notably lower implementation climate scores across subscales and roles compared to other settings may underlie the vast evidence to practice gap in obstetrics. In order to successfully implement practices that reduce maternal morbidity, we may need to focus on building educational support and rewarding EBP utilization on labor and delivery units, with an emphasis on nursing clinicians.

Agreement Between Experts and an Untrained Crowd for Identifying Dermoscopic Features Using a Gamified App: Reader Feasibility Study.

BACKGROUND: Dermoscopy is commonly used for the evaluation of pigmented lesions, but agreement between experts for identification of dermoscopic structures is known to be relatively poor. Expert labeling of medical data is a bottleneck in the development of machine learning (ML) tools, and crowdsourcing has been demonstrated as a cost- and time-efficient method for the annotation of medical images. OBJECTIVE: The aim of this study is to demonstrate that crowdsourcing can be used to label basic dermoscopic structures from images of pigmented lesions with similar reliability to a group of experts. METHODS: First, we obtained labels of 248 images of melanocytic lesions with 31 dermoscopic "subfeatures" labeled by 20 dermoscopy experts. These were then collapsed into 6 dermoscopic "superfeatures" based on structural similarity, due to low interrater reliability (IRR): dots, globules, lines, network structures, regression structures, and vessels. These images were then used as the gold standard for the crowd study. The commercial platform DiagnosUs was used to obtain annotations from a nonexpert crowd for the presence or absence of the 6 superfeatures in each of the 248 images. We replicated this methodology with a group of 7 dermatologists to allow direct comparison with the nonexpert crowd. The Cohen κ value was used to measure agreement across raters. RESULTS: In total, we obtained 139,731 ratings of the 6 dermoscopic superfeatures from the crowd. There was relatively lower agreement for the identification of dots and globules (the median κ values were 0.526 and 0.395, respectively), whereas network structures and vessels showed the highest agreement (the median κ values were 0.581 and 0.798, respectively). This pattern was also seen among the expert raters, who had median κ values of 0.483 and 0.517 for dots and globules, respectively, and 0.758 and 0.790 for network structures and vessels. The median κ values between nonexperts and thresholded average-expert readers were 0.709 for dots, 0.719 for globules, 0.714 for lines, 0.838 for network structures, 0.818 for regression structures, and 0.728 for vessels. CONCLUSIONS: This study confirmed that IRR for different dermoscopic features varied among a group of experts; a similar pattern was observed in a nonexpert crowd. There was good or excellent agreement for each of the 6 superfeatures between the crowd and the experts, highlighting the similar reliability of the crowd for labeling dermoscopic images. This confirms the feasibility and dependability of using crowdsourcing as a scalable solution to annotate large sets of dermoscopic images, with several potential clinical and educational applications, including the development of novel, explainable ML tools.

A Quality Improvement Project to Reduce Events of Visitor Escalation in the Intensive Care Nursery.

BACKGROUND: Escalating and aggressive visitor behaviors have become increasingly common in healthcare settings nationally, negatively impacting staff and patients alike. Most healthcare providers do not innately possess the specific skills to manage such behaviors. Management of escalating and aggressive behaviors presents a particularly bedeviling challenge when staff safety must be balanced with the needs of parent-neonate bonding. PURPOSE: In the Intensive Care Nursery (ICN), the frequency of aggressive and hostile incidents from visitors increased such that the staff felt frustrated by and uneasy about their work environment. METHODS: The ICN convened an interprofessional team to strategize interventions aimed at consistently managing aggressive behavior and supporting the staff after aggressive and/or hostile visitor encounters. FINDINGS: Following staff education and training, the unit launched a de-escalation management algorithm in July 2018 that assisted in identifying high-risk families at admission and drove consistent action and management of all visitor behaviors. In the 12 months following the intervention, the frequency of behavioral escalation decreased by 75% and staff perception of safety increased by 25%. IMPLICATIONS FOR PRACTICE: Collaborating with staff to design consistent strategies to manage aggressive and escalating visitor behavior can improve safety and improve employee satisfaction in the ICN. IMPLICATIONS FOR RESEARCH: Additional research on the effectiveness of the algorithm in other ICNs and alternative areas of practice is needed. Furthermore, validation of a staff perception survey measuring the impact of escalating visitor behaviors on employees would be an important next step in this research.Video abstract available athttps://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=43.

Tunable Interfacial Properties in Silk Ionomer Microcapsules with Tailored Multilayer Interactions.

Microencapsulation techniques represent a critical step in realizing highly controlled transport of functional materials in multiphase systems. The first demonstration of microcapsules prepared from minimally grafted silk ionomers (silk fibroin modified with cationic/anionic charge groups) are presented here. These tailored biomacromolecules have shown significantly increased biocompatibility over traditional polyelectrolytes and heavily grafted silk ionomers, but the low grafting density had previously limited attempts to fabricate stable microcapsules. In addition, the first microcapsules from polyethylene-glycol-grafted silk ionomers are fabricated and the corresponding impact on microcapsule behavior is demonstrated. The materials are shown to exhibit pH-responsive properties, with the microcapsules demonstrating an approx. tenfold decrease in stiffness and an approx. threefold change in diffusion coefficient when moving from acidic to basic buffer. Finally, the effect of assembly conditions of the microcapsules are shown to play a large role in determining final properties, with microcapsules prepared in acidic buffers showing lower roughness, stiffness, and an inversion in transport behavior (i.e., permeability decreases at higher pH).

Dual-Excitation Nanocellulose Plasmonic Membranes for Molecular and Cellular SERS Detection.

We demonstrate that cellulose nanofiber (CNF) biomaterials with high transparency and mechanical robustness can be combined with gold nanorods to form a multifunctional porous membrane for dual-mode surface-enhanced Raman scattering (SERS) detection of both small molecules and cells. The nanoporous nature of the nanofiber membranes allows for effective molecular filtration and preconcentration of the analytes, further boosting the SERS performance. Specifically, because of the low fluorescence and Raman background of the CNF matrix, extremely low loading density of gold nanorods can be used. The nanorod assemblies within the CNF network can be resonantly driven by a 532 nm laser (transverse plasmonic mode) and near resonantly driven at by a 785 nm laser (longitudinal mode), facilitating dual operational modes at two excitation wavelengths. The shorter wavelength excitation mode yields better Raman scattering efficiency and has been demonstrated to be capable of detecting rhodamine 6G (R6G) dyes down to picomolar concentrations. On the other hand, the longer wavelength excitation mode provides autofluorescence suppression for the better detection of microorganisms such as Escherichia coli, shortening the required integration time from hours to minutes. Upon drastically lowering the spectral background noise and utilizing nanofiltration, the plasmonic CNF membranes reported here show significantly improved SERS sensitivity and detection fidelity as compared to traditional metal, metal oxide, synthetic polymer, and paper SERS substrates.

Results of the 2016 International Skin Imaging Collaboration International Symposium on Biomedical Imaging challenge: Comparison of the accuracy of computer algorithms to dermatologists for the diagnosis of melanoma from dermoscopic images.

BACKGROUND: Computer vision may aid in melanoma detection. OBJECTIVE: We sought to compare melanoma diagnostic accuracy of computer algorithms to dermatologists using dermoscopic images. METHODS: We conducted a cross-sectional study using 100 randomly selected dermoscopic images (50 melanomas, 44 nevi, and 6 lentigines) from an international computer vision melanoma challenge dataset (n = 379), along with individual algorithm results from 25 teams. We used 5 methods (nonlearned and machine learning) to combine individual automated predictions into "fusion" algorithms. In a companion study, 8 dermatologists classified the lesions in the 100 images as either benign or malignant. RESULTS: The average sensitivity and specificity of dermatologists in classification was 82% and 59%. At 82% sensitivity, dermatologist specificity was similar to the top challenge algorithm (59% vs. 62%, P = .68) but lower than the best-performing fusion algorithm (59% vs. 76%, P = .02). Receiver operating characteristic area of the top fusion algorithm was greater than the mean receiver operating characteristic area of dermatologists (0.86 vs. 0.71, P = .001). LIMITATIONS: The dataset lacked the full spectrum of skin lesions encountered in clinical practice, particularly banal lesions. Readers and algorithms were not provided clinical data (eg, age or lesion history/symptoms). Results obtained using our study design cannot be extrapolated to clinical practice. CONCLUSION: Deep learning computer vision systems classified melanoma dermoscopy images with accuracy that exceeded some but not all dermatologists.

Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1.

Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti-PD-1 mAb nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti-PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell- and B-cell-mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383-9. ©2016 AACR.

Technology and Technique Standards for Camera-Acquired Digital Dermatologic Images: A Systematic Review.

IMPORTANCE: Photographs are invaluable dermatologic diagnostic, management, research, teaching, and documentation tools. Digital Imaging and Communications in Medicine (DICOM) standards exist for many types of digital medical images, but there are no DICOM standards for camera-acquired dermatologic images to date. OBJECTIVE: To identify and describe existing or proposed technology and technique standards for camera-acquired dermatologic images in the scientific literature. EVIDENCE REVIEW: Systematic searches of the PubMed, EMBASE, and Cochrane databases were performed in January 2013 using photography and digital imaging, standardization, and medical specialty and medical illustration search terms and augmented by a gray literature search of 14 websites using Google. Two reviewers independently screened titles of 7371 unique publications, followed by 3 sequential full-text reviews, leading to the selection of 49 publications with the most recent (1985-2013) or detailed description of technology or technique standards related to the acquisition or use of images of skin disease (or related conditions). FINDINGS: No universally accepted existing technology or technique standards for camera-based digital images in dermatology were identified. Recommendations are summarized for technology imaging standards, including spatial resolution, color resolution, reproduction (magnification) ratios, postacquisition image processing, color calibration, compression, output, archiving and storage, and security during storage and transmission. Recommendations are also summarized for technique imaging standards, including environmental conditions (lighting, background, and camera position), patient pose and standard view sets, and patient consent, privacy, and confidentiality. Proposed standards for specific-use cases in total body photography, teledermatology, and dermoscopy are described. CONCLUSIONS AND RELEVANCE: The literature is replete with descriptions of obtaining photographs of skin disease, but universal imaging standards have not been developed, validated, and adopted to date. Dermatologic imaging is evolving without defined standards for camera-acquired images, leading to variable image quality and limited exchangeability. The development and adoption of universal technology and technique standards may first emerge in scenarios when image use is most associated with a defined clinical benefit.

Effects on skills and practice from a web-based skin cancer course for primary care providers.

BACKGROUND: Melanoma incidence and mortality is a growing concern. Better recognition and management of skin cancer by primary care providers (PCPs) could help, but studies suggest they would benefit from additional education. Effective educational programs are needed. METHODS: We developed and conducted a voluntary before-and-after evaluation of a 1- to 2-hour interactive, web-based course in skin cancer detection for practicing, board-certified PCPs (http://www.skinsight.com/info/for_professionals/dermatology-education-resources). Voluntary participants' ability to diagnose and manage skin cancer was assessed using pretests, immediate tests, and 6-month posttests. The effect on actual practice patterns was assessed using participants' patient panels: referrals or visits to dermatology and skin biopsies during the 6 months after the course were compared with those during the same period before the course. RESULTS: The mean age of the 54 participants was 50.5 years (standard deviation, 11.1); 54% were women and 52% were Asian. The mean score for appropriate diagnosis and management increased from 36.1% to 46.7% (odds ratio, 1.6; 95% confidence interval, 1.4-1.9), with greatest improvement in benign lesions, from 32.1% to 46.3% (odds ratio, 1.9; 95% confidence interval, 1.6-2.4). Dermatology referrals for suspicious lesions or new visits by participants' patients decreased at both sites after the course (from 630 to 607 and from 726 to 266, respectively). CONCLUSIONS: This course improved skills in practicing PCPs. Improvement was greatest in the diagnosis and appropriate management of benign lesions and dermatology utilization decreased.

Microinvasive melanoma: cutaneous pharmacotherapeutic approaches.

Surgical excision is the treatment of choice for primary melanomas and radiation therapy is the accepted alternative for the subset of lesions not amenable to surgery. With the recent rise in melanoma incidence, especially in the elderly, there are a growing number of cases that are neither amenable to surgery nor radiation therapy. In this article, we review pharmacotherapeutic approaches to microinvasive melanoma (invasive radial growth phase melanoma) that might be considered in such circumstances. There are no approved drugs for the treatment of primary melanoma and randomized controlled trials with 5 or more years of follow-up have not been performed. The limited studies and numerous case series in the literature on pharmacologic treatment of primary melanoma have focused on topical therapies. Accordingly, we provide a review of the potential pharmacotherapeutic agents in the treatment of microinvasive melanoma by extrapolating from the available limited literature on the use of fluorouracil, azelaic acid, retinoic acid derivatives, interferon (IFN)-α, imiquimod, and other agents for melanoma in situ, invasive melanoma, and epidermotropic melanoma metastases. Our review indicates that topical fluorouracil and tretinoin are not effective as single agents. The efficacy of azelaic acid, tazarotene, cidofovir, and intralesional IFN-α, interleukin-2, and IFN-ß is undefined. Imiquimod is the most studied and promising agent; however, optimal dosage, therapeutic regimen, and survival rates are unknown. In the face of a growing demand for non-surgical treatments, formal clinical trials are needed to ascertain the role of pharmacotherapeutic agents in the treatment of microinvasive melanoma.

Influence of time on dermoscopic diagnosis and management.

BACKGROUND/OBJECTIVES: Dermoscopy aids in clinical decision-making. However, time pressure is a common reason precluding its use. We evaluated the effect of time on lesion recognition and management decisions utilising clinical and dermoscopic images. METHOD: In all, 100 dermoscopic images were presented to 15 dermatologists with experience in dermoscopy and seven non-experts (dermatology residents). Each lesion was displayed thrice in succession. The dermoscopic image was initially presented for 1 s (t1). The same dermoscopic image was shown again without time constraints (t2) and then a final time with additional images of the clinical context (t3). Participants provided a diagnosis, their level of confidence and biopsy predilection after evaluating each image. RESULTS: For benign lesions, both groups rarely changed their diagnosis. However, an improvement in the number of correct benign diagnoses was observed when the lesion was shown in a clinical context. For malignant lesions, both groups improved when more time and clinical context was given; nevertheless, non-experts were more likely to change the diagnosis towards the correct one as more time was given and tended to perform more biopsies, in particular of benign lesions. Limitations were a small number of participants and an artificial study setting. CONCLUSION: Dermoscopy uses analytical and non-analytical reasoning approaches. We suggest that non-analytical reasoning is employed when rapid clinical decisions need to be made, especially during the evaluation of benign lesions. We conclude that dermoscopy is relatively rapid and non-time-consuming technique that adds relevant information and guides clinicians towards appropriate management decisions.