Collapsars as a major source of r-process elements.

The production of elements by rapid neutron capture (r-process) in neutron-star mergers is expected theoretically and is supported by multimessenger observations1-3 of gravitational-wave event GW170817: this production route is in principle sufficient to account for most of the r-process elements in the Universe4. Analysis of the kilonova that accompanied GW170817 identified5,6 delayed outflows from a remnant accretion disk formed around the newly born black hole7-10 as the dominant source of heavy r-process material from that event9,11. Similar accretion disks are expected to form in collapsars (the supernova-triggering collapse of rapidly rotating massive stars), which have previously been speculated to produce r-process elements12,13. Recent observations of stars rich in such elements in the dwarf galaxy Reticulum II14, as well as the Galactic chemical enrichment of europium relative to iron over longer timescales15,16, are more consistent with rare supernovae acting at low stellar metallicities than with neutron-star mergers. Here we report simulations that show that collapsar accretion disks yield sufficient r-process elements to explain observed abundances in the Universe. Although these supernovae are rarer than neutron-star mergers, the larger amount of material ejected per event compensates for the lower rate of occurrence. We calculate that collapsars may supply more than 80 per cent of the r-process content of the Universe.

Updates on coding in dermatology.

Correct coding is an important component of effective dermatology practice management. Over the past several years there have been updates to many commonly used codes within dermatology. This review highlights many of these updates, such as: the skin biopsy codes have been subdivided to reflect the different biopsy techniques. The definition of complex linear repairs has been updated and clarified. Outpatient and inpatient evaluation and management visits have new coding guidelines to determine level of care. Dermatopathology consultation codes have been updated and category III codes related to digital pathology have been created. Understanding the details and nuances of each of these categories of codes is vital to ensuring appropriate coding is performed.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND:  Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE:  To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS:  A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS:  The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION:  The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12):54-60.   doi:10.36849/JDD.7691.

Jets from Neutron-Star Merger Remnants and Massive Blue Kilonovae.

We perform three-dimensional general-relativistic magnetohydrodynamic simulations with weak interactions of binary neutron-star (BNS) mergers resulting in a long-lived remnant neutron star, with properties typical of galactic BNS and consistent with those inferred for the first observed BNS merger GW170817. We demonstrate self-consistently that within ≲30 ms postmerger magnetized (σ∼5-10) incipient jets emerge with asymptotic Lorentz factor Γ∼5-10, which successfully break out from the merger debris within ≲20 ms. A fast (v≲0.6c), magnetized (σ∼0.1) wind surrounds the jet core and generates a UV/blue kilonova precursor on timescales of hours, similar to the precursor signal due to free neutron decay in fast dynamical ejecta. Postmerger ejecta are quickly dominated by magnetohydrodynamically driven outflows from an accretion disk. We demonstrate that, within only 50 ms postmerger, ≳2×10^{-2}M_{⊙} of lanthanide-free, quasispherical ejecta with velocities ∼0.1-0.2c is launched, yielding a kilonova signal consistent with GW170817 on timescales of ≲5 d.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE: To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS: A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION: The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12): doi:10.36849/JDD.7691e.

International Dermatology Outcome Measures (IDEOM) - Report from the 2022 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) is a non-profit organization dedicated to the advancement of evidence-based, consensus-driven outcome measures in dermatological diseases. Researchers and stakeholders from various backgrounds collaborate to develop these objective benchmark metrics to further advance treatment and management of dermatological conditions. SUMMARY: The 2022 IDEOM Annual Meeting was held on June 17-18, 2022. Leaders and stakeholders from the hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, cutaneous lymphoma, and psoriatic disease workgroups discussed the progress of their respective outcome-measures research. This report summarizes each workgroup's updates from 2022 and their next steps as established during the 2022 IDEOM Annual Meeting. J Drugs Dermatol. 2023;22(12):1153-1159 doi:10.36849/JDD.7615.

An interpersonal neurobiology perspective on the mind and mental health: personal, public, and planetary well-being.

This article outlines an Interpersonal Neurobiology (IPNB) perspective on the fundamental components that comprise mental health and promote well-being. The central aim of this paper is to answer essential but often overlooked questions related to the field of mental health, such as: What is the mind? What is the basis of well-being? What is the self and how does it develop? We will offer scientific support for the IPNB position that the mind is relational and embodied and that integration is the basis of mental health. It will also describe how the self extends beyond the individual, arising from and inextricably connected to the social, cultural and planetary systems in which we exist. IPNB is not a form of therapy; rather, it is a framework that focuses on deepening our understanding of the mind and human development across the lifespan. Drawing from interdisciplinary principles from a range of fields including physics, mathematics, neuroscience, and psychology, we will provide a practical view of the underlying basis of mental suffering and the scientific mechanisms of change to improve mental well-being. These core principles are building blocks of clinical evaluation and treatment that can be applied across multiple theoretical orientations and client populations. The special emphasis in this article is on the issue of psychache as an underlying cause of suicide and its relationship to personal, public and planetary health.

Validation of a Market-Approved Artificial Intelligence Mobile Health App for Skin Cancer Screening: A Prospective Multicenter Diagnostic Accuracy Study.

BACKGROUND: Mobile health (mHealth) consumer applications (apps) have been integrated with deep learning for skin cancer risk assessments. However, prospective validation of these apps is lacking. OBJECTIVES: To identify the diagnostic accuracy of an app integrated with a convolutional neural network for the detection of premalignant and malignant skin lesions. METHODS: We performed a prospective multicenter diagnostic accuracy study of a CE-marked mHealth app from January 1 until August 31, 2020, among adult patients with at least one suspicious skin lesion. Skin lesions were assessed by the app on an iOS or Android device after clinical diagnosis and before obtaining histopathology. The app outcome was compared to the histopathological diagnosis, or if not available, the clinical diagnosis by a dermatologist. The primary outcome was the sensitivity and specificity of the app to detect premalignant and malignant skin lesions. Subgroup analyses were conducted for different smartphone types, the lesion's origin, indication for dermatological consultation, and lesion location. RESULTS: In total, 785 lesions, including 418 suspicious and 367 benign control lesions, among 372 patients (50.8% women) with a median age of 71 years were included. The app performed at an overall 86.9% (95% CI 82.3-90.7) sensitivity and 70.4% (95% CI 66.2-74.3) specificity. The sensitivity was significantly higher on the iOS device compared to the Android device (91.0 vs. 83.0%; p = 0.02). Specificity calculated on benign control lesions was significantly higher than suspicious skin lesions (80.1 vs. 45.5%; p < 0.001). Sensitivity was higher in skin fold areas compared to smooth skin areas (92.9 vs. 84.2%; p = 0.01), while the specificity was higher for lesions in smooth skin areas (72.0 vs. 56.6%; p = 0.02). CONCLUSION: The diagnostic accuracy of the mHealth app is far from perfect, but is potentially promising to empower patients to self-assess skin lesions before consulting a health care professional. An additional prospective validation study, particularly for suspicious pigmented skin lesions, is warranted. Furthermore, studies investigating mHealth implementation in the lay population are needed to demonstrate the impact on health care systems.

International Dermatology Outcome Measures (IDEOM): Report from the 2020 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) initiative is a non-profit organization that aims to develop evidence-based outcome measurements to evaluate the impact of treatments for patients with dermatological disease. IDEOM includes all key stakeholders in dermatology (patient, physician, industry, insurer, and government) during the process of developing such outcome measurements. SUMMARY: Here, we provide an update of IDEOM activities that were presented at the 2020 IDEOM Virtual Annual Meeting (October 23-24, 2020). During the meeting, multiple IDEOM workgroups (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) shared their progress to date, as well as future directions in developing and validating Patient-Reported Outcome Measures. Updates on demonstrating efficacy in clinicals trials by the US Food and Drug Administration are also summarized. KEY MESSAGES: In this report, we summarize the work presented by each IDEOM workgroup (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) at the 2020 IDEOM Virtual Annual Meeting.

2020 IDEOM Annual Meeting: Actinic Keratosis Stakeholders Survey Identifies Gaps in Research and Care.

This is a report of the survey results from the International Dermatology Outcome Measures (IDEOM) actinic keratosis (AK) workgroup. The purpose of the survey was to compile a list of gaps within AK care and management that require refinement. The results were discussed at the IDEOM annual meeting held virtually on October 23–24, 2020. This built a framework with which the AK workgroup, which consisted of physicians, patients, and pharmaceutical scientists, discussed at length in their breakout session at the meeting. The electronic survey was distributed to patients, pharmaceutical scientists, and leading physician experts in the field via email on September 22, 2020, with a deadline of October 2, 2020. The survey consisted of three open-ended prompts concerning key gaps and/or unmet needs in (1) the care of AKs, (2) outcome measurement of AKs in clinical trials and, (3) the measurement of AKs in clinical practice. The results were qualitative, with a response rate of 47%. Responses included reform of outcome measures for clinical trials, a methodology for evaluating the efficacy of preventative measures, and a comparison of treatments to establish a treatment protocol, among other efforts. This paper will also provide a brief overview of the current state of the AK outcome measures, emphasizing the heterogeneity of the measures and detailing the AK workgroup's future efforts to create a reliable and applicable core outcome measure set. J Drugs Dermatol. 2022;21(2):128-134. doi:10.36849/JDD.6360.

International Dermatology Outcome Measures (IDEOM): Report from the 2021 Annual Meeting.

BACKGROUND: International Dermatology Outcome Measures (IDEOM) is a non-profit organization founded in 2013. It is composed of researchers and stakeholders who work to develop evidenced-based outcome measures to enhance research and treatment recommendations of dermatologic diseases. SUMMARY: The 2021 IDEOM Virtual Annual Meeting occurred from November 19-20, 2021. Contributions were made by leaders and stakeholders from the psoriasis, psoriatic arthritis, pediatric hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, and cutaneous lymphoma workgroups. The psoriasis, psoriatic arthritis, and actinic keratosis workgroups provided an overview of their respective instruments for treatment satisfaction and symptom measurement. The inaugural meetings of the itch, alopecia areata, and cutaneous lymphoma workgroups identified unmet needs of their respective diseases and future goals. The acne, vitiligo, and pediatric hidradenitis suppurativa workgroups discussed concerns of quality of life, instruments for symptom measurement, and screening tools. Additionally, a representative from the US Food and Drug Administration was in attendance and presented an update on topical drugs and generics. This report provides a summary of workgroup updates from the past year and future directions established during the meeting. KEY MESSAGES: This report summarizes progress made by each IDEOM workgroup at the 2021 IDEOM Virtual Annual Meeting. J Drugs Dermatol. 2022;21(8):867-874. doi:10.36849/JDD.6974.

Neutrino Fast Flavor Conversions in Neutron-Star Postmerger Accretion Disks.

A compact accretion disk may be formed in the merger of two neutron stars or of a neutron star and a stellar-mass black hole. Outflows from such accretion disks have been identified as a major site of rapid neutron-capture (r-process) nucleosynthesis and as the source of "red" kilonova emissions following the first observed neutron-star merger GW170817. We present long-term general-relativistic radiation magnetohydrodynamic simulations of a typical postmerger accretion disk at initial accretion rates of M[over ˙]∼1 M_{⊙} s^{-1} over 400 ms postmerger. We include neutrino radiation transport that accounts for the effects of neutrino fast flavor conversions dynamically. We find ubiquitous flavor oscillations that result in a significantly more neutron-rich outflow, providing lanthanide and 3rd-peak r-process abundances similar to solar abundances. This provides strong evidence that postmerger accretion disks are a major production site of heavy r-process elements. A similar flavor effect may allow for increased lanthanide production in collapsars.

A Novel Skin Moisture Management Strategy.

An important function of skin is prevention of water loss. When the normal skin barrier breaks down, strategies to treat dry skin include occlusives and humectants. An important physiological process for retaining water in epidermal cells is the taurine transporter (TauT). The TauT is activated within minutes after the skin is exposed to irritation, dehydration, ultraviolet radiation, and other stressors. A novel product comprising two patented technologies delivers cytoprotective osmoregulation and ingredients for optimum moisture management (Tetros® ULTRA, Intense Hydration for Stressed Skin; TetraDerm™ Group LLC, Grosse Pointe, MI). The product has been formulated with natural physiological lipid ceramides, free fatty acids, and cholesterol esters, which restore and protect the stratum corneum moisture barrier. It also contains a retinoid activator of the TauT to stimulate osmoregulation. The selected lipids and lipid precursors are present in the product in ratios that resemble the natural complexity of biological membranes. The product is also formulated with different nano- and micro-compartments that deliver hydrophilic and hydrophobic actives together, with different rates and depth of delivery, without changing composition or concentrations of excipients. The formulation enables penetration through stratum corneum and epidermis without disturbing normal skin barrier function. Controlled ingredient release and penetration depth enhance the capability of lipid precursors to promote skin lipid biosynthesis. These product characteristics lend themselves to widespread application in numerous dermatologic disorders without compromising the normal barrier function of the skin. J Drugs Dermatol. 2021;20(7):752-754. doi:10.36849/JDD.5749.

Delayed Metastatic Polypoid Nodular Melanoma Diagnosis During COVID-19 Pandemic, Successful Treatment With Surgery and Nivolumab.

Patients with polypoid (pedunculated) melanoma have the poorest 5-year survival rate compared with all other variants of nodular melanoma, presenting with increased thickness, incidence of metastasis, and rates of ulceration. There are few published reports regarding the pathogenesis and treatment of polypoid melanomas. We report the successful treatment of a rapidly developing red nodular polypoid melanoma with metastasis using surgery followed by anti-PD-1 antibody nivolumab in a SARS-CoV-2-positive patient who delayed seeking care due to the COVID-19 pandemic. J Drugs Dermatol. 2021;20(12):1343-1345. doi:10.36849/JDD.6071.

Variability in Wound Care Recommendations Following Dermatologic Procedures.

BACKGROUND: Dermatologists routinely perform office-based surgical procedures that result in cutaneous wounds. Wound care instructions are an important resource for postoperative patients. As there is no consensus on the ideal wound care regimen after dermatologic procedures, recommendations may vary. OBJECTIVE: To evaluate the current recommendations for wound care following dermatologic procedures. METHODS: The authors conducted a cross-sectional assessment of dermatology wound care handouts available online. The handouts were evaluated based on predefined parameters: topical agent recommendations for wound healing, caution against topical antibiotic use, and discussion of scarring, infection, bleeding, analgesia, and lifestyle considerations. RESULTS: A total of 169 handouts were evaluated. The majority (84%) recommended the application of petrolatum-based products, specifically Vaseline (75%) and Aquaphor (43%). Nearly half (43%) recommended the use of topical antibiotics, whereas 24% advised patients to avoid antibiotic ointments. Handouts variably addressed scarring (36%), infection (72%), bleeding (69%), pain (66%), and lifestyle modifications (64%). CONCLUSION: The instructions provided in dermatology patient handouts are highly variable, with various topical agents being recommended for wound healing. Topical antibiotics are not indicated for prophylaxis in clean dermatologic procedures but are still widely used. Greater efforts should be made to ensure that patients receive consistent and evidence-based wound care guidance.

Therapies for Psoriasis: Clinical and Economic Comparisons.

BACKGROUND: Clinical and economic comparisons of therapies for plaque psoriasis are regularly updated following each new devel- opment in the field. With the recent availability of a novel accessory (Multi Micro DoseTM [MMD®] tip) for the 308nm excimer laser (XTRAC®, Strata Skin Sciences, Horsham, PA), which can determine and deliver an optimal therapeutic dose (OTDTM) of ultraviolet-B light in an improved protocol, the need for comparative health-economic assessment recurs. To this end, a comprehensive evaluation of treatment-related costs was undertaken from the payer perspective. Results show that outcomes are influenced by many factors; most importantly, the severity and extent of disease, treatment selection, and patient preference, as well as compliance, adherence, and persistence with care. Among study comparators, the 308nm excimer laser – XTRAC – with its latest MMD enhancement, is safe and delivers incremental clinical benefits with the potential for significant cost savings. These benefits are particularly relevant today in the context of SARS-CoV-2 virus and the COVid-19 pandemic. J Drugs Dermatol. 2020;19(11):1101-1108. doi:10.36849/JDD.2020.5510.

The evolving maintenance of certification process: update on the financial status of the medical boards.

Medical board organizations have accumulated large asset balances, in part due to the monetization of physician board recertification, as well as capital gains in positive investment conditions. Physicians across the country have raised concerns regarding the effectiveness and efficiency of existing recertification processes, to which the American Board of Medical Specialties and independent accreditation boards have responded with newly instituted changes. The present article analyzes the publicly available F990 tax forms of the medical boards in an effort to provide data to the ongoing debate. Although some boards have begun to mobilize assets in recent years, many continue to accumulate wealth. It remains to be seen whether the new recertification programs will bring about change or perpetuate organizational wealth.

Efficacy and safety of ingenol disoxate gel in field treatment of actinic keratosis on full face, scalp or large area (250 cm2) on the chest: results of four phase 3 randomized controlled trials.

INTRODUCTION: Actinic keratosis (AK) is a skin condition arising from chronic exposure to ultraviolet light and may lead to the development of malignancies. This trial aimed to evaluate efficacy and safety of ingenol disoxate gel (IngDsx, 0.018% for face/chest [FC]; 0.037% for scalp [S]), versus vehicle. METHODS: Four identical phase 3 trials in patients with AK on the full face/up to 250cm2 of chest or full balding scalp, with an initial 8-week period and 12-month follow-up, were conducted. FC and S trials were pooled for analysis. The primary endpoint was complete clearance at Week 8. RESULTS: Across trials, 616 patients were randomized to FC and 626 to S, with 410 and 420 assigned to receive IngDsx, respectively. In the FC and S trials, 25.9% and 24.5% of patients in the IngDsx group, respectively, achieved the primary endpoint. IngDsx was relatively well tolerated. During extended follow-up, there were more identified non-melanoma skin malignancies in the IngDsx group than vehicle group; HR: 2.38 (95% CI: 1.28, 4.41). CONCLUSION: Treatment with IngDsx was superior to vehicle on all clinical endpoints, patient-reported and cosmetic outcomes. During the 12-month follow-up, slightly increased skin malignancies in the treatment area were identified, potentially due to unintentional detection bias.

Assessment of Provider Utilization Through Skin Biopsy Rates.

BACKGROUND: There have been recent claims of overdiagnosis and unnecessary treatment in dermatology. One potential manifestation of overutilization would be providers who perform numerous biopsies per patient. OBJECTIVE: To identify the frequency of skin biopsy rate outliers. MATERIALS AND METHODS: Data on biopsy rates at the individual provider level were obtained from Medicare Provider Utilization and Payment Data Public Use Files. The total number of biopsies for each provider was obtained by summing the number of claimed biopsy services for each unique National Provider Identifier. The visit count for each provider was obtained by summing all evaluation and management services claimed. Provider biopsy rates were calculated by dividing the total number of biopsies associated with each National Provider Identifier by the corresponding visit count. RESULTS: The mean provider biopsy rate was 0.31 services per visit, or approximately 1 biopsy every 3 visits. Defining outliers as providers who averaged 3 or more biopsies per visit, there were 38 outliers out of 18,260 providers. Physicians had a lower mean biopsy rate than nonphysician clinicians (p = 1.70E-28). CONCLUSION: Contrary to claims, the authors' results do not indicate widespread overutilization of skin biopsy services.

Corrigendum: Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month followup of negative test results and utility data from a large US registry study.

The revised version of the article corrected Figure 2. This change appears in the revised online PDF copy of this article.