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.

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.

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.

Adjuvant radiotherapy may not significantly change outcomes in high-risk cutaneous squamous cell carcinomas with clear surgical margins: A systematic review and meta-analysis.

BACKGROUND: The role of adjuvant radiotherapy for high-risk cutaneous squamous cell carcinomas after surgery with negative margins is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis examining the risk of poor outcomes for patients treated with surgery alone versus surgery and adjuvant radiotherapy. METHODS: A comprehensive search of articles was executed in PubMed, Embase, and the Cochrane Database. Random-effected meta-analyses were conducted. RESULTS: Thirty-three studies comprising 3867 high-risk cutaneous squamous cell carcinomas were included. There were no statistically significant differences in poor outcomes between the surgery only group and surgery with adjuvant radiotherapy group. Estimates for local recurrence for the surgery alone group versus the surgery with adjuvant radiotherapy group were 15.2% (95% confidence interval [CI], 6.3%-27%) versus 8.8% (95% CI, 1.6%-20.9%); for regional metastases, 11.5% (95% CI, 7.2%-16.7%) versus 4.4% (95% CI, 0%-18%); for distant metastases, 2.6% (95% CI, 0.6%-6%) versus 1.7% (95% CI, 0.2%-4.5%); and for disease-specific deaths, 8.2% (95% CI, 1.2%-20.6%) versus 19.7% (95% CI, 3.8%-43.7%), respectively. LIMITATIONS: Retrospective nature of most studies with the lack of sufficient patient-specific data. CONCLUSIONS: For patients with high-risk cutaneous squamous cell carcinomas treated with margin-negative resection, there were no significant differences in poor outcomes between the surgery only group and the surgery with adjuvant radiotherapy group. Randomized controlled trials are necessary to define the benefit of adjuvant radiotherapy in this setting.

Multi-Session Anodal Prefrontal Transcranial Direct Current Stimulation does not Improve Executive Functions among Older Adults.

OBJECTIVE: Findings from single-session online studies highlighted the potential of using anodal prefrontal transcranial direct current stimulation (tDCS) to enhance executive functions (EF) in the context of aging. However, tDCS must be executed as a multi-session offline intervention to ascertain its viability in this context. Relatedly, findings from multi-session studies remained inconclusive. To this end, we examined the effects of multi-session anodal prefrontal tDCS on EF in an intervention. METHOD: The intervention consisted of 15 sessions; in each, healthy older participants (Agemean = 66.7) received either 15 min of 1.5 mA tDCS (Ncompleted = 35) or sham stimulation (Ncompleted = 33) while performing EF training tasks. EF measures were assessed at baseline, post-intervention, and 1-month follow-up. Hierarchical linear models were used to examine the effect of tDCS on EF outcomes. RESULTS: Both groups of participants did not differ significantly in side effect ratings and attendance. There were no significant tDCS-associated gains in any EF outcomes in the intervention. CONCLUSIONS: Multi-session prefrontal tDCS did not lead to any significant gains in EF in the current intervention. More research is needed to optimize the use of tDCS before it can be effectively used to enhance EF among older adults.

Correlation Between Original Biopsy Pathology and Mohs Intraoperative Pathology.

BACKGROUND: The pathology observed on initial biopsy specimens for nonmelanoma skin cancer (NMSC), specifically the tumor subtype, weighs heavily into the selection of the treatment modality. Recognizing aggressive features on intraoperative Mohs micrographic surgery (MMS) frozen sections that were not indicated on initial biopsy reports is not uncommon. To date, there is limited data describing this discrepancy. OBJECTIVE: To investigate the frequency and nature of incongruity between the pathology seen in initial biopsies and intraoperative Mohs sections, providing information that will potentially impact skin cancer treatment and biopsy recommendations. METHODS: Retrospective chart review of cases of NMSC referred for MMS at the authors' institution over a 1-year period, recording changes between tumor subtypes observed at biopsy and those observed during MMS. RESULTS: Cases (50.5%) (n = 163) changed aggressiveness. Of these, 33% (n = 108) were more aggressive, whereas 17% (n = 55) were less aggressive. CONCLUSION: A substantial discrepancy was observed between preoperative biopsy and intraoperative pathology, including a significant portion tumors that became more aggressive. These results suggest that treatment modalities without margin control may not provide adequate treatment for a considerable number of NMSC based on preoperative tumor type alone.

Perceived loneliness among older adults with mild cognitive impairment.

BACKGROUND: The high prevalence of mild cognitive impairment (MCI) in Hong Kong, as previously reported, requires verification. Furthermore, the relationship between loneliness, depression, and cognitive impairment with regards to MCI are unclear. The present study aims to establish the prevalence of MCI in a community sample in Hong Kong and determine if participants with MCI feel significantly lonelier, even after depression has been taken into consideration. METHODS: Participants from a community sample (N = 376) were assessed with subjective and objective measures of cognitive impairments to determine whether the criteria had been met for MCI. The MCI cases are then compared with age, sex, and education-matched controls on subjective measures of loneliness and depression. RESULTS: A total of 66 (17.6%) participants were diagnosed with MCI. These participants reported significantly higher levels of perceived loneliness and depression compared to the matched controls. Differences between groups in loneliness remained significant, even after depression levels have been controlled. CONCLUSIONS: Loneliness is implicated in MCI. The relationship between loneliness and MCI is, at least, partially independent of depression. The implications of these finding are discussed.

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.

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.

Mohs micrographic surgery for cutaneous metastasis of breast cancer.

To our knowledge, this is the first report of metastatic cutaneous breast cancer treatment with MMS. Regardless of the prognosis, complete clearance of metastatic lesions around the eyes is necessary for functional, cosmetic, and palliative purposes. In conjunction with systemic treatment, MMS can play an important role for metastatic cutaneous cancers.