Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways.

PURPOSE: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. EXPERIMENTAL DESIGN: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip (STS) extracts and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays. RESULTS: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFN-gamma mRNA in patients with lichenoid (p<0.0001) and psoriasiform dermatitis (p<0.01) as compared to patients without ircAEs, while the highest IL-13 mRNA levels were detected in the eczema (p<0.0001, compared to control). IL-17A mRNA was selectively increased in psoriasiform (p<0.001), lichenoid (p<0.0001), bullous dermatitis (p<0.05) and MPR (p<0.001), compared to control. Distinct cytokine profiles were confirmed in STS and plasma. Analysis determined increased skin/plasma IL-4 cytokine in pruritus, skin IL-13 in eczema, plasma IL-5 and IL-31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2-cytokine targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo. CONCLUSIONS: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.

Consent and Identifiability for Patient Images in Research, Education, and Image-Based Artificial Intelligence.

This survey study reports the perspectives and preferences of US adults regarding use of photographs of their skin in medical research, education, and development of image-based artificial intelligence (AI).

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.

Gender Disparities Among Craniofacial Surgeons.

To delineate career differences between genders of practicing plastic surgeons who have completed craniofacial fellowship given the known disparities in surgeons' professional and personal lives and an already lengthy residency training, there is concern that less women may commit to further fellowship training.Craniofacial fellowship programs were contacted to identify graduates and an internet search was attempted where information was not available. Surgeon profiles and literature databases were used to obtain practice demographics and publications.Accredited fellowships were identified through the American Society of Craniofacial Surgeons directory.Program responses along with internet searches identified 201 graduates from 26 programs, of which 132 (66%) were men and 69 (34%) were women. On average, male graduates had 7.1 years in practice versus 6.6 years for females graduates (P = .176). There were significant differences between average number of publications (24.7 publications for males vs 14.1 for females, P = .009) and academic practice (46% males vs 64% females, P = .018). A similar percentage of males and females held leadership positions (13% males vs 16%, P = .552).Despite similar years in practice, men had significantly higher publications while women were significantly more likely to practice in an academic setting. Females are increasing their representation in academia and leadership within the craniofacial community. However, efforts must still be directed at increasing exposure to craniofacial surgery and supporting research and leadership pursuits earlier on during their careers.

Expanding the Utilization of Low-Dose Computed Tomography in Plastic and Reconstructive Surgery Based on Validated Practices Among Surgical Specialties.

INTRODUCTION: As computed tomography (CT) usage increases, so have concerns over radiation-induced malignancy. To mitigate these risks, low-dose CT (LDCT) has emerged as a versatile alternative by other specialties, although its use in plastic surgery remains sparse. This study aimed to investigate validated uses of LDCT across surgical specialties and extrapolate these insights to expand its application for plastic surgeons. METHODS: A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using search terms "low dose CT" OR "low dose computed tomography" AND "surgery," where the name of each surgical specialty was substituted for word "surgery" and each specialty term was searched separately in combination with the 2 CT terms. Data on radiation dose, outcomes, and level of evidence were collected. Validated surgical applications were correlated with similar procedures and diagnostic tests performed routinely by plastic surgeons to extrapolate potential applications for plastic surgeons. RESULTS: A total of 3505 articles were identified across surgical specialties, with 27 ultimately included. Depending on the application, use of LDCT led to a 25% to 97% reduction in radiation dose and all studies reported noninferior image quality and diagnostic capability compared with standard-dose CT. Potential identified uses included the following: evaluation of soft tissue infections, preoperative and postoperative management of facial and hand fractures, flap design, 3D modeling, and surgical planning. DISCUSSION: Low-dose CT is a valid imaging alternative to standard-dose CT. Expanded utilization in plastic surgery should be considered to minimize the iatrogenic effects of radiation and to promote patient safety without compromising outcomes.

Ocean acidification alters properties of the exoskeleton in adult Tanner crabs, Chionoecetes bairdi.

Ocean acidification can affect the ability of calcifying organisms to build and maintain mineralized tissue. In decapod crustaceans, the exoskeleton is a multilayered structure composed of chitin, protein and mineral, predominately magnesian calcite or amorphous calcium carbonate (ACC). We investigated the effects of acidification on the exoskeleton of mature (post-terminal-molt) female southern Tanner crabs, Chionoecetes bairdi Crabs were exposed to one of three pH levels - 8.1, 7.8 or 7.5 - for 2 years. Reduced pH led to a suite of body region-specific effects on the exoskeleton. Microhardness of the claw was 38% lower in crabs at pH 7.5 compared with those at pH 8.1, but carapace microhardness was unaffected by pH. In contrast, reduced pH altered elemental content in the carapace (reduced calcium, increased magnesium), but not the claw. Diminished structural integrity and thinning of the exoskeleton were observed at reduced pH in both body regions; internal erosion of the carapace was present in most crabs at pH 7.5, and the claws of these crabs showed substantial external erosion, with tooth-like denticles nearly or completely worn away. Using infrared spectroscopy, we observed a shift in the phase of calcium carbonate present in the carapace of pH 7.5 crabs: a mix of ACC and calcite was found in the carapace of crabs at pH 8.1, whereas the bulk of calcium carbonate had transformed to calcite in pH 7.5 crabs. With limited capacity for repair, the exoskeleton of long-lived crabs that undergo a terminal molt, such as C. bairdi, may be especially susceptible to ocean acidification.