Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell Carcinoma.

Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effects, which often lead to treatment discontinuation and subsequent relapse in patients with LaBCC. Prolonged remission was previously reported in patients with LaBCCs who underwent surgical debulking before starting vismodegib. In this study, we enrolled 4 patients with LaBCC who underwent debulking followed by vismodegib therapy to assess their clinical outcomes and analyze the cutaneous molecular changes occurring as a result of surgical intervention. After LaBCC debulking, patients underwent a punch biopsy of residual basal cell carcinoma tissue 1 week later. RT-qPCR analysis of 24 Notch and Wnt signaling-associated genes revealed elevated PTCH1, HEY2, LGR6, FZD2, LEF1, ALCAM, and RUNX1 expressions in follow-up biopsies compared with those in patient-matched debulked tissue. Immunoblot and immunostaining further confirmed elevated Notch signaling in follow-up biopsy tissue compared with that in patient-matched debulked tumor tissue. Patients 1, 3, and 4 displayed a clinical response to debulking followed by vismodegib, whereas patient 2 was lost to follow-up after debulking. These findings suggest that surgical manipulation of LaBCCs is correlated with molecular alterations in signaling pathways associated with cellular reprogramming.

The effect of bright light therapy on major depressive disorder: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The increasing prevalence of major depressive disorder (MDD) has led to increased demand for psychotherapy and pharmacotherapy, yet concerns were raised regarding the cost and accessibility to these therapies. Bright light therapy (BLT) has shown promise in mitigating depressive symptoms of non-seasonal affective disorders. This meta-analysis gathered evidence from randomised controlled trials (RCTs) to assess the effectiveness of BLT on patients with non-seasonal MDD. METHODS: Five databases were systematically searched. The primary outcome of the meta-analysis was the endpoint depression score from the BLT and control treatment groups, with the remission and response rates as the secondary outcomes. Results are presented in standardised mean difference (SMD) and log odd ratio. Subgroup analyses compared the effects of trial length and the length of daily exposure. RESULTS: Results on 15 RCTs between 1996 and 2024 with 883 patients showed positive effects of BLT on alleviating depressive symptoms (SMD = 0.48, 95 % CI [0.22, 0.74], p <.001). Trials that lasted two weeks or less or those with 60 minutes or more of daily exposure were associated with higher therapeutic effectiveness. BLT was also associated with a higher response rate at the end of the trial. CONCLUSION: This meta-analysis offers positive evidence that favours BLT in alleviating depressive symptoms in MDD, suggesting that it could be a convenient and easily accessible treatment modality to augment psychotherapy and pharmacotherapy.

The effect of transcranial direct current and magnetic stimulation on fear extinction and return of fear: A meta-analysis and systematic review.

BACKGROUND: We conducted a meta-analysis and qualitative review on the randomized controlled trials investigating the effects of transcranial direct current stimulation and transcranial magnetic stimulation on fear extinction and the return of fear in non-primate animals and humans. METHODS: The meta-analysis was conducted by searching PubMed, Web of science, PsycINFO, and Cochrane Library and extracting fear response in the active and sham groups in the randomized controlled trials. The pooled effect size was quantified by Hedges' g using a three-level meta-analytic model in R. RESULTS: We identified 18 articles on the tDCS effect and 5 articles on the TMS effect, with 466 animal subjects and 621 human subjects. Our findings show that tDCS of the prefrontal cortex significantly inhibit fear retrieval in animal models (Hedges' g = -0.50). In human studies, TMS targeting the dorsolateral/ventromedial prefrontal cortex has an inhibiting effect on the return of fear (Hedges' g = -0.24). LIMITATIONS: The limited number of studies and the heterogeneous designs of the selected studies made cross-study and cross-species comparison difficult. CONCLUSIONS: Our findings shed light on the optimal non-invasive brain stimulation protocols for targeting the neural circuitry of threat extinction in humans.

Histologic Hitchhikers: A Review of Common Exogenous Artifacts Encountered During Mohs Micrographic Surgery.

BACKGROUND: Exogenous artifacts can interfere with accurate histologic tissue evaluation on frozen sections during Mohs micrographic surgery (MMS). Mohs surgeons should be aware of these anomalies to avoid potential misdiagnoses. OBJECTIVE: To review exogenous artifacts encountered in frozen tissue pathology during MMS. METHODS: A literature search was conducted in PubMed to identify studies reporting on exogenous artifacts encountered during MMS and a list of previously described exogenous artifacts was compiled. A retrospective examination of frozen histology slides from recent Mohs cases at the authors' institution was performed to obtain illustrative examples of these artifacts, supplemented by formalin-fixed paraffin-embedded samples when frozen examples could not be found. RESULTS: Exogenous artifacts represent foreign bodies that have been externally introduced into the skin or artifacts resulting from other external factors. If frozen section evaluation is inaccurate, overdiagnosis can occur during MMS, resulting in unnecessary layers, larger margins, and more complex reconstructions. These exogenous tissue changes can mimic inflammatory processes and melanocytic or keratinocyte malignancies on histology. CONCLUSION: Exogenous artifacts are common findings during margin assessment in Mohs micrographic surgery. The resulting histological findings can be confusing but correlating them with the clinical and surgical history often reassures surgeons. Recognizing these artifacts facilitates accurate diagnosis and promotes optimal patient care.

Mohs surgeon workforce survey: a spectrum of clinical, academic, and leadership activities.

Workforce adequacy for Mohs micrographic surgery (MMS) is not fully understood. The purpose of this study was to describe the current spectrum of clinical, academic, advocacy and leadership activities through a survey of members of the American College of Mohs Surgery (ACMS). The ACMS membership was electronically sent a 43-question anonymous survey between January and May 2023 and there was a 10.7% response rate representing 184 members across 37 states. Nearly 90% are board certified in micrographic dermatologic surgery and 10.3% indicate that they practice in a rural setting (57.1% suburban and 32.6% urban). The median number of half-day surgeons performed Mohs surgery is 6 and nearly half of Mohs surgeons work in a dermatology-only medical group (48.4%), do no use immunohistochemical stains (60.3%), and do not participate in a multidisciplinary tumor board (58.7%). Many respondents indicate they have capacity in their clinical schedules to accommodate more cases and the reasons are multifactorial.

The role of consciousness in threat extinction learning.

Extinction learning is regarded as a core mechanism underlying exposure therapy. The extent to which learned threats can be extinguished without conscious awareness is a controversial and on-going debate. We investigated whether implicit vs. explicit exposure to a threatened stimulus can modulate defence responses measured using pupillometry. Healthy participants underwent a threat conditioning paradigm in which one of the conditioned stimuli (CS) was perceptually suppressed using continuous flash suppression (CFS). Participants' pupillary responses, CS pleasantness ratings, and trial-by-trial awareness of the CS were recorded. During Extinction, participants' pupils dilated more in the trials in which they were unaware of the CS than in those in which they were aware of it (Cohen's d = 0.57). After reinstatement, the percentage of fear recovery was greater for the CFS-suppressed CS than the CS with full awareness. The current study suggests that the modulation of fear responses by extinction with reduced visual awareness is weaker compared to extinction with full perceptual awareness.

Well-Being and Professional Fulfillment in Mohs Surgeons: An Explanatory Sequential Mixed-Method Design Study.

BACKGROUND: There are limited data evaluating specific themes of well-being and professional fulfillment in Mohs surgeons. OBJECTIVE: To identify factors that drive occupational distress and those that promote well-being and professional fulfillment among Mohs surgeons. METHODS: This is an explanatory sequential mixed-method study, using semistructured individual interviews. Common drivers of physician well-being and fulfillment were identified based on the independent assessment of the coding in the interview transcripts. RESULTS: This study reports the following qualitative themes: (1) gratitude for the chosen profession and relationships, (2) unrealistic standards of perfection that may have contributed to past career success but are unattainable and create emotional burden, and (3) ability to practice in a manner aligned with personal values promotes professional fulfillment. CONCLUSION: This study suggests that gratitude, self-compassion, and ability to practice in a manner aligned with personal values promote well-being and professional fulfillment in Mohs surgeons. Notably, we found that unrealistic standards of perfection and personal-organization practice incongruences contribute to burnout.

Photoaging and Topical Rejuvenation.

Photoaging is a complex process of skin changes associated with chronic ultraviolet exposure. Prevention with photoprotection and treatment with topical retinoids are the core components of a topical antiaging regimen. Other topicals such as hydroquinone, vitamin C, niacinamide, and alpha hydroxyl acid can be added based on specific concerns. However, caution must be used with some of these products as the stability and absorption are major considerations. A simple topical regimen will reduce irritability and enhance compliance.

Bone Wax as a Physical Hemostatic Agent.

Achieving hemostasis in cutaneous surgery on bony or irregular surfaces can be challenging; typical pressure dressings that act by mechanical occlusion with petrolatum gauze can be inadequate. We offer the use of bone wax as a practical hemostatic agent that can be (1) molded to provide ideal occlusion and pressure without adhering to wound surfaces and (2) painlessly and simply removed.

Implicit threat learning involves the dorsolateral prefrontal cortex and the cerebellum

Background/Objective: Most studies investigating the neural correlates of threat learning were carried out using an explicit Pavlovian conditioning paradigm where declarative knowledge on contingencies between conditioned (CS) and unconditioned stimuli (US) is acquired. The current study aimed at understanding the neural correlates of threat conditioning when contingency awareness is limited or even absent. Method: We conducted an fMRI report of threat learning in an implicit associative learning paradigm called multi-CS conditioning, in which a number of faces were associated with aversive screams (US) such that participants could not report contingencies between the faces and the screams. Results: The univariate results showed support for the recruitment of threat-related regions including the dorsolateral prefrontal cortex (dlPFC) and the cerebellum during acquisition. Further analyses by the multivariate representational similarity technique identified learning-dependent changes in the bilateral dlPFC. Conclusion: Our findings support the involvement of the dlPFC and the cerebellum in threat conditioning that occurs with highly limited or even absent contingency awareness. (AU)

Numerous Ulcerated Plaques of the Trunk and Extremities in a Patient Receiving Long-term Hydroxyurea Therapy.

A woman in her 80s initially presented with numerous, primarily photodistributed, crusted, and ulcerated plaques of the trunk and extremities and a medical history of essential thrombocytosis treated with hydroxyurea for 14 years. What is your diagnosis?

Implicit threat learning involves the dorsolateral prefrontal cortex and the cerebellum.

Background/Objective: Most studies investigating the neural correlates of threat learning were carried out using an explicit Pavlovian conditioning paradigm where declarative knowledge on contingencies between conditioned (CS) and unconditioned stimuli (US) is acquired. The current study aimed at understanding the neural correlates of threat conditioning when contingency awareness is limited or even absent. Method: We conducted an fMRI report of threat learning in an implicit associative learning paradigm called multi-CS conditioning, in which a number of faces were associated with aversive screams (US) such that participants could not report contingencies between the faces and the screams. Results: The univariate results showed support for the recruitment of threat-related regions including the dorsolateral prefrontal cortex (dlPFC) and the cerebellum during acquisition. Further analyses by the multivariate representational similarity technique identified learning-dependent changes in the bilateral dlPFC. Conclusion: Our findings support the involvement of the dlPFC and the cerebellum in threat conditioning that occurs with highly limited or even absent contingency awareness.

Cognitive bias modification for paranoia (CBM-pa): a randomised controlled feasibility study in patients with distressing paranoid beliefs.

BACKGROUND: Cognitive Bias Modification for paranoia (CBM-pa) is a novel, theory-driven psychological intervention targeting the biased interpretation of emotional ambiguity associated with paranoia. Study objectives were (i) test the intervention's feasibility, (ii) provide effect size estimates, (iii) assess dose-response and (iv) select primary outcomes for future trials. METHODS: In a double-blind randomised controlled trial, sixty-three outpatients with clinically significant paranoia were randomised to either CBM-pa or an active control (text reading) between April 2016 and September 2017. Patients received one 40 min session per week for 6 weeks. Assessments were given at baseline, after each interim session, post-treatment, and at 1- and 3-months post-treatment. RESULTS: A total of 122 patients were screened and 63 were randomised. The recruitment rate was 51.2%, with few dropouts (four out of 63) and follow-up rates were 90.5% (1-month) and 93.7% (3-months). Each session took 30-40 min to complete. There was no statistical evidence of harmful effects of the intervention. Preliminary data were consistent with efficacy of CBM-pa over text-reading control: patients randomised to the intervention, compared to control patients, reported reduced interpretation bias (d = -0.48 to -0.76), improved symptoms of paranoia (d = -0.19 to -0.38), and lower depressed and anxious mood (d = -0.03 to -0.29). The intervention effect was evident after the third session. CONCLUSIONS: CBM-pa is feasible for patients with paranoia. A fully powered randomised control trial is warranted.

Cohort study assessing the predictive value of a research year vs additional degree in dermatology.

Taking a gap year to obtain an additional degree or for research is becoming increasingly popular among medical students pursuing dermatology to bolster residency application competitiveness. The purpose of this study was to determine whether doing so influences future academic achievement and career trajectory. A list of dermatologists who achieved board certification in 2010 was obtained from the American Board of Dermatology. Information regarding additional post-graduate degrees, research years, fellowship specialization, practice setting, publication number, and H-index were obtained using publicly available data. Additional degrees were associated with higher research productivity, higher H-index, and practicing at teaching hospitals while taking a research year was only associated with a higher H-index. This data can be used to further inform medical students wishing to achieve high levels of research productivity and careers at teaching institutions and residency programs wishing to recruit such applicants.