Clinical implication of PRAME immunohistochemistry in differentiating melanoma in situ and dysplastic nevus in non-acral nevus-associated melanoma in situ: An institutional experience and meta-analysis.

INTRODUCTION: PReferentially expressed Antigen in MElanoma (PRAME) has shown utility in differentiating benign from malignant melanocytic neoplasms. In this study, we investigated the clinical significance of PRAME expression in dysplastic nevi (DN) and nevus-associated melanoma in situ (MIS). METHODS: We included 172 DN and 38 nevus-associated MIS from our institutional archive. PRAME positive expression was defined as nuclear staining in at least 75% of melanocytes. In addition, relevant studies from PubMed and Web of Science were incorporated into a meta-analysis using the random-effects model to assess PRAME expression in MIS and DN. RESULTS: Our institutional data revealed that 71.1% of nevus-associated MIS cases exhibited positive PRAME expression in the MIS components, whereas all DN components were negative for PRAME. 5.7% of cases diagnosed as DN in our cohort demonstrated diffuse positivity for PRAME. Notably, MIS associated with DN displaying epidermal and dermal components displayed a higher likelihood of PRAME positivity compared to those arising on a background of DN with solely epidermal (junctional) components (84% vs. 46%, p = 0.024). The meta-analysis indicated that the pooled PRAME positivity in MIS and DN was 54.5% and 1.9%, respectively. CONCLUSION: PRAME is a valuable immunohistochemical marker for differentiating MIS from DN, particularly in the context of nevus-associated MIS.

A paradoxical misperception of relative motion.

Motion perception is considered a hyperacuity. The presence of a visual frame of reference to compute relative motion is necessary to achieve this sensitivity [Legge, Gordon E., and F. W. Campbell. "Displacement detection in human vision." Vision Research 21.2 (1981): 205-213.]. However, there is a special condition where humans are unable to accurately detect relative motion: images moving in a direction consistent with retinal slip where the motion is unnaturally amplified can, under some conditions, appear stable [Arathorn, David W., et al. "How the unstable eye sees a stable and moving world." Journal of Vision 13.10.22 (2013)]. In this study, we asked: Is world-fixed retinal image background content necessary for the visual system to compute the direction of eye motion to render in the percept images moving with amplified slip as stable? Or, are non-visual cues sufficient? Subjects adjusted the parameters of a stimulus moving in a random trajectory to match the perceived motion of images moving contingent to the retina. Experiments were done with and without retinal image background content. The perceived motion of stimuli moving with amplified retinal slip was suppressed in the presence of visual content; however, higher magnitudes of motion were perceived under conditions with no visual cues. Our results demonstrate that the presence of retinal image background content is essential for the visual system to compute its direction of motion. The visual content that might be thought to provide a strong frame of reference to detect amplified retinal slips, instead paradoxically drives the misperception of relative motion.

Participation in Clinical Trials Among Academic Dermatologists Affiliated With Veterans Affairs Hospitals: Survey Study.

Background: Clinical trials have led to the development of new and effective therapies for many dermatologic conditions. To our knowledge, there is no published study that has quantified and described the degree of involvement in clinical trials among academic dermatologists and their university affiliates. Objective: The purpose of this study was to characterize the involvement of academic dermatology departments in clinical trials research. Methods: An online survey was sent to 211 Veterans Affairs (VA)-employed dermatologists. It comprised 20 questions related to the number of clinical trials, support staff dedicated to clinical research, skin diseases studied, and the effect of the COVID-19 pandemic on conducting clinical research. Three rounds of survey invitations were sent over a 3-month period (March to May 2021). Data from all survey responses were reviewed for quantitative and descriptive analyses of the key outcome measures. Results: A total of 48 dermatologists completed the survey and provided their university affiliations and details of involvement in clinical trials research. Over half of participants (n=25, 58.1%) with a university affiliate reported that their affiliated dermatology department had a dedicated clinical trials unit. Basal cell carcinoma was the most frequently studied skin condition (n=9, 18.8%), followed by atopic dermatitis and psoriasis (n=4, 8.3% each); 66.7% of participants reported no current clinical trials participation. Of those conducting clinical trials, 87% (n=18) noted that COVID-19 was a barrier to conducting trials, with 52.2% (n=11) citing disrupted or decreased trials due to the pandemic. Conclusions: Although many dermatologists with university affiliations reported having a dedicated clinical trials unit at their institution, a majority of those surveyed reported not taking part in any active trials. Overall, the diseases investigated in academic clinical trials appear to follow national trends, though some of the top dermatological diseases are underrepresented in clinical trials research. A key limitation of our study was the low response rate (~23%) and that the survey responses from the sample of VA-based dermatologists may not be generalizable to all academic dermatology departments in the United States. The effect of the COVID-19 pandemic appeared to play a significant role in disrupting active trials.

Cemiplimab for Locally Advanced Cutaneous Squamous Cell Carcinoma: A Case Series of 3 Unique Scenarios.

Cemiplimab, a monoclonal antibody directed against programmed death receptor 1 (PD-1), has shown promising results in cutaneous squamous cell carcinoma (cSCC). In a nonrandomized trial where cemiplimab 3 mg/kg was given every 2 weeks for up to 96 weeks, a 44% response rate was noted. This case series discusses 3 unique scenarios of patients with advanced cSCC treated with cemiplimab. The first case is of an end stage kidney disease (ESKD) patient with failed living donor kidney transplant who had developed recurrent cSCC despite several excisions and topical 5-flurouracil and acitretin therapy. He received 8 cycles of cemiplimab leading to resolution. This case serves as an example of the safety and efficacy of cemiplimab in a complex patient who is a kidney transplant recipient on hemodialysis. The second case describes an elderly gentleman with inoperable cSCC initially treated with radiotherapy who later received 9 cycles of cemiplimab for recurrent metastatic disease with excellent response. This case supports the safe and effective use of cemiplimab in an elderly patient. In the third case, cSCC presented itself as a large fungating mass that would have otherwise necessitated limb amputation and was successfully treated with 18 cycles of cemiplimab. This case highlights the dramatic response to cemiplimab obviating the need for surgical intervention and resulting in limb salvage.

Dermatology residency research policies: A 2021 national survey.

BACKGROUND: In this follow-up study to previous work, the authors survey the availability of key measures and resources pertaining to residency research in U.S. Accreditation Council for Graduate Medical Education-accredited dermatology residency programs, including potential policy changes following the COVID-19 pandemic. OBJECTIVE: The chief objective of this survey was to evaluate and compare dermatology programs' resident research requirements and guidelines. METHODS: This cross-sectional study employed a 13-item survey administered online in early 2021 to assess the degree to which dermatology residency programs require and support their new physician graduates in scholarly research endeavors. RESULTS: A total of 32 program directors representing 30 dermatology residency programs (30 of 138 accredited programs contacted [22%]) responded to the survey. Almost all programs described quality improvement project requirements for residents and were able to provide funding for resident conference participation. Most programs also reported resident publication requirements and the availability of research electives. However, the vast majority did not have required research rotations or a formal mentorship program. The COVID-19 pandemic did not have a substantial impact on residency research requirements. CONCLUSION: Our survey provides objective data about the current dermatology resident research requirements across the United States. These findings may prove valuable to prospective applicants, residency programs, and accrediting agencies in improving, advancing, and structuring dermatology residency guidelines and resources with the aim of encouraging new physician trainees to pursue research.

A Mutated PB1 Residue 319 Synergizes with the PB2 N265S Mutation of the Live Attenuated Influenza Vaccine to Convey Temperature Sensitivity.

Current influenza vaccines have modest efficacy. This is especially true for current live attenuated influenza vaccines (LAIV), which have been inferior to the inactivated versions in recent years. Therefore, a new generation of live vaccines may be needed. We previously showed that a mutation at PB1 residue 319 confers enhanced temperature sensitivity and attenuation in an LAIV constructed in the genetic background of the mouse-adapted Influenza A Virus (IAV) strain A/PR/8/34 (PR8). Here, we describe the origin/discovery of this unique mutation and demonstrate that, when combined with the PB2 N265S mutation of LAIV, it conveys an even greater level of temperature sensitivity and attenuation on PR8 than the complete set of attenuating mutations from LAIV. Furthermore, we show that the combined PB1 L319Q and PB2 N265S mutations confer temperature sensitivity on IAV polymerase activity in two different genetic backgrounds, PR8 and A/Cal/04/09. Collectively, these findings show that the PB2 LAIV mutation synergizes with a mutation in PB1 and may have potential utility for improving LAIVs.