Use of an elastic-scattering spectroscopy and artificial intelligence device in the assessment of lesions suggestive of skin cancer: A comparative effectiveness study.

Background: Skin cancer is the most common form of cancer worldwide. As artificial intelligence (AI) expands its scope within dermatology, leveraging technology may aid skin cancer detection. Objective: To assess the safety and effectiveness of an elastic-scattering spectroscopy (ESS) device in evaluating lesions suggestive of skin cancer. Methods: This prospective, multicenter clinical validation study was conducted at 4 US investigational sites. Patients with skin lesions suggestive of melanoma and nonmelanoma skin cancers were clinically assessed by expert dermatologists and evaluated by a device using AI algorithms comparing current ESS lesion readings with training data sets. Statistical analyses included sensitivity, specificity, AUROC, negative predictive value (NPV), and positive predictive value (PPV). Results: Overall device sensitivity was 97.04%, with subgroup sensitivity of 96.67% for melanoma, 97.22% for basal cell carcinoma, and 97.01% for squamous cell carcinoma. No statistically significant difference was found between the device and dermatologist performance (P = .8203). Overall specificity of the device was 26.22%. Overall NPV of the device was 89.58% and PPV was 57.54%. Conclusion: The ESS device demonstrated high sensitivity in detecting skin cancer. Use of this device may assist primary care clinicians in assessing suspicious lesions, potentially reducing skin cancer morbidity and mortality through expedited and enhanced detection and intervention.

Rash and Poor Wound Healing After Mastectomy.

A patient who had recently undergone bilateral mastectomy had erythema, edema, pain, pruritus, serous fluid drainage at the incision sites, and an erythematous papulovesicular rash on the trunk and extremities. A skin swab bacterial culture result was negative, and the skin findings did not improve with antibiotics. What is the diagnosis and what would you do next?

Proposed guidelines for appropriate utilization of superficial radiation therapy in management of skin cancers. Zemtsov-Cognetta criteria.

OBJECTIVE: To develop appropriate use criteria (AUC) for the treatment of basal cell and squamous cell carcinoma by superficial radiation therapy (SRT) technique. MATERIAL AND METHODS: Delphi-type discussion of the experts. RESULTS: Presented in Figure 1. CONCLUSION: These AUCs are in compliance both with the position statement of the American Academy of Dermatology (AAD) and the ASTRO Clinical Practice Guideline on this subject. It is further recommended that SRT will be only performed by either a dermatologist who is board certified in Mohs surgery (MDS) and who had adequate SRT training or by radiation oncologists. Hopefully, this publication will stimulate further discussion on this topic.

A Rare Presentation of Dermatofibrosarcoma Protuberans of the Scalp Treated with "Slow-Mohs" Micrographic Surgery.

Dermatofibrosarcoma protuberans (DFSP) is a rare, fibrohistiocytic tumor with intermediate malignancy.1 While these tumors are slow-growing and only metastasize in 6% of cases,2 they are often locally destructive, with relatively high local recurrence rates after initial excision. Overall annual incidence rates in the US are 0.8-4.1 per million person-years,2 though incidence among African Americans is nearly double that of Caucasians.3 DFSP is most commonly seen on the trunk (42-50%), followed by the extremities (30-42%) and, rarely, on the head and neck (10-15%).2,4 Other studies report that DFSP of the scalp accounts for under 5% of total cases.5 However, the head and neck region is reported to have the highest tendency to recur locally, roughly 50-75% of cases.4 Further, DFSP tumors on the scalp have the potential to metastases to the brain,4 thus highlighting the importance for these tumors to be correctly diagnosed and treated early on. Partly due to its rarity and also its tendency to mimic other mainly benign lesions clinically, DFSP is often misdiagnosed, leading to years of delay in proper treatment and otherwise likely avoidable sequelae.6 We describe a rare presentation of DFSP on the scalp of a 45-year-old African American woman successfully treated with "slow-Mohs" micrographic surgery. We also discuss the most common misdiagnoses for DFSP and scenarios when this tumor should be included in the differential and subsequent work-up.J Drugs Dermatol. 2022;21(5):534-535. doi:10.36849/JDD.6719.

Identification of cell wall synthesis inhibitors active against Mycobacterium tuberculosis by competitive activity-based protein profiling.

The identification and validation of a small molecule's targets is a major bottleneck in the discovery process for tuberculosis antibiotics. Activity-based protein profiling (ABPP) is an efficient tool for determining a small molecule's targets within complex proteomes. However, how target inhibition relates to biological activity is often left unexplored. Here, we study the effects of 1,2,3-triazole ureas on Mycobacterium tuberculosis (Mtb). After screening ∼200 compounds, we focus on 4 compounds that form a structure-activity series. The compound with negligible activity reveals targets, the inhibition of which is functionally less relevant for Mtb growth and viability, an aspect not addressed in other ABPP studies. Biochemistry, computational docking, and morphological analysis confirms that active compounds preferentially inhibit serine hydrolases with cell wall and lipid metabolism functions and that disruption of the cell wall underlies biological activity. Our findings show that ABPP identifies the targets most likely relevant to a compound's antibacterial activity.

Vismodegib as Eye-Sparing Neoadjuvant Treatment for Locally Advanced Periocular Basal Cell Carcinoma.

Locally-advanced periocular basal cell carcinoma (BCC) pose many therapeutic challenges due to the need to preserve functionality and cosmesis of the orbit and periocular area. Surgical excision and subsequent orbital exenteration are two recognized modalities of treatment. Vismodegib is currently an FDA-approved monotherapy for locally-advanced and metastatic BCC. We present a case of the use of vismodegib as neoadjuvant therapy prior to surgical excision of a locally-advanced periocular recurrent BCC in a 75-year-old male. The patient’s tumor successfully responded to vismodegib allowing surgical excision with clear margins. The orbit was saved in a patient who otherwise would have required complete orbital exenteration. J Drugs Dermatol. 20(5):552-554. doi:10.36849/JDD.5661.

Comparison of Grenz ray and photodynamic therapy for field treatment of actinic keratoses on the forearm: A case series.

BACKGROUND: Actinic Keratosis is an intraepidermal neoplasm that represents the second most common reason for dermatologic visits in the United States. Sustained clearance with existing therapies is highly variable. OBJECTIVE: To assess the effects of combination and monotherapy with photodynamic therapy (PDT), grenz ray therapy, and PDT with microneedling (microchannel skin system) for actinic damage of the dorsal forearms and hands. METHODS: Full ethics approval was obtained through a Human Subjects Committee. Four patients with diffuse actinic field damage on their forearms and hands were recruited for the study. The dorsal forearm and hand from the elbow to the metacarpophalangeal joint were divided into four equal sections. Section 1 was treated with PDT. Section 2 was treated with grenz ray. Section 3 was treated with PDT plus microneedling. Section 4 was treated with grenz ray and PDT with microneedling. Lesion counts were recorded with transparent grids, photographed and evaluated by the same investigator at baseline, 1, 2, 3 and 6 months. RESULTS: At month 6 post treatment, lesion counts, as a per cent reduction from baseline, were 91.7% in section 1 (PDT); 97.3% in section 2 (grenz ray); 92.9% in section 3 (PDT + microneedle); and 93.9% in section 4 (grenz ray + PDT + microneedle). CONCLUSION: The greatest reduction occurred in the grenz ray monotherapy section and the second greatest reduction in the grenz ray, PDT, microneedling section. Further research on the efficacy of grenz ray therapy for field treatment of actinic keratosis of the forearms and hands is needed.

Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium.

A decline in stem cell function impairs tissue regeneration during ageing, but the role of the stem-cell-supporting niche in ageing is not well understood. The small intestine is maintained by actively cycling intestinal stem cells that are regulated by the Paneth cell niche1,2. Here we show that the regenerative potential of human and mouse intestinal epithelium diminishes with age owing to defects in both stem cells and their niche. The functional decline was caused by a decrease in stemness-maintaining Wnt signalling due to production of Notum, an extracellular Wnt inhibitor, in aged Paneth cells. Mechanistically, high activity of mammalian target of rapamycin complex 1 (mTORC1) in aged Paneth cells inhibits activity of peroxisome proliferator activated receptor α (PPAR-α)3, and lowered PPAR-α activity increased Notum expression. Genetic targeting of Notum or Wnt supplementation restored function of aged intestinal organoids. Moreover, pharmacological inhibition of Notum in mice enhanced the regenerative capacity of aged stem cells and promoted recovery from chemotherapy-induced damage. Our results reveal a role of the stem cell niche in ageing and demonstrate that targeting of Notum can promote regeneration of aged tissues.

Consensus Guidelines on the Use of Superficial Radiation Therapy for Treating Nonmelanoma Skin Cancers and Keloids.

Background: The use of superficial radiation therapy (SRT) has experienced a renaissance for treating nonmelanoma skin cancers (NMSCs) and recurrent keloids; however, published treatment guidelines are lacking. Objective: The objective of this work was to provide consensus guidelines on the use of SRT for treating NMSC and recurrent keloids based on a review of the literature and expert opinion. Methods and Materials: A search of the medical literature was performed to obtain published information on the use of SRT for review. A group of qualified dermatologists convened to discuss their views on the use of SRT for the treatment of NMSCs and recurrent keloids. The various guidelines were considered to have consensus based on a supermajority two-thirds vote. The final consensus guidelines are thus based on the medical literature, when available, and expert opinions. Results: Agreement on consensus guidelines was reached for numerous aspects of SRT use, including appropriate tumor types for SRT; anatomical areas suitable for SRT; energy, fractions, and scheduling recommendations for SRT; use of SRT in the presence of comorbidities; safety factors; and treatment recommendations for recurrent keloids, based the literature and on both the opinions of the expert group and a survey of experienced users. Conclusion: Consensus was reached that SRT is a safe and effective treatment for basal cell and squamous cell carcinomas and should be considered as the first-line form of radiation treatment. Postsurgical treatment of keloid excision suture lines with SRT significantly reduces keloid recurrence rates.

Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan.

Phenotypic screening has identified small-molecule modulators of aging, but the mechanism of compound action often remains opaque due to the complexities of mapping protein targets in whole organisms. Here, we combine a library of covalent inhibitors with activity-based protein profiling to coordinately discover bioactive compounds and protein targets that extend lifespan in Caenorhabditis elegans. We identify JZL184-an inhibitor of the mammalian endocannabinoid (eCB) hydrolase monoacylglycerol lipase (MAGL or MGLL)-as a potent inducer of longevity, a result that was initially perplexing as C. elegans does not possess an MAGL ortholog. We instead identify FAAH-4 as a principal target of JZL184 and show that this enzyme, despite lacking homology with MAGL, performs the equivalent metabolic function of degrading eCB-related monoacylglycerides in C. elegans. Small-molecule phenotypic screening thus illuminates pure pharmacological connections marking convergent metabolic functions in distantly related organisms, implicating the FAAH-4/monoacylglyceride pathway as a regulator of lifespan in C. elegans.

Global Portrait of Protein Targets of Metabolites of the Neurotoxic Compound BIA 10-2474.

Clinical investigation of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 resulted in serious adverse neurological events. Structurally unrelated FAAH inhibitors tested in humans have not presented safety concerns, suggesting that BIA 10-2474 has off-target activities. A recent activity-based protein profiling (ABPP) study revealed that BIA 10-2474 and one of its major metabolites inhibit multiple members of the serine hydrolase class to which FAAH belongs. Here, we extend these studies by performing a proteome-wide analysis of covalent targets of BIA 10-2474 metabolites. Using alkynylated probes for click chemistry-ABPP in human cells, we show that des-methylated metabolites of BIA 10-2474 covalently modify the conserved catalytic cysteine in aldehyde dehydrogenases, including ALDH2, which has been implicated in protecting the brain from oxidative stress-related damage. These findings indicate that BIA 10-2474 and its metabolites have the potential to inhibit multiple mechanistically distinct enzyme classes involved in nervous system function.