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BACKGROUND: Prior literature notes increased rates of delayed diagnosis and increased morbidity and mortality for patients with Fitzpatrick skin types IV to VI with melanoma and nonmelanoma skin cancers, noting surgical delays and larger postoperative defects. Dyschromia is among the most common concerns in Fitzpatrick skin types IV to VI. OBJECTIVE: To consolidate the latest information on patient counseling, suture selection, and interventions related to postoperative pigmentary complications for Fitzpatrick skin types IV to VI. MATERIALS AND METHODS: A literature review was conducted using the Embase, Scopus, Google Scholar, PubMed from 2014 to 2025 focused on surgical considerations, pathophysiology of surgical considerations, hypopigmented scars, suture selection, postinflammatory hyperpigmentation, and treatment and counseling of postsurgical complications or outcomes in Fitzpatrick skin types IV to VI. RESULTS: Preoperative factors that may worsen wound healing include the use of skin lightning agents. Intraoperative factors include secondary intention healing and full-thickness grafts., Opting for direct or flap closure and noninflammatory suture selection minimizes postoperative dyschromia. Postoperative considerations include Ultraviolet A/B and visible light photoprotection counseling and suture removal timing. Promising treatments need further research including microdermal grafting for hypopigmented scars. CONCLUSION: Special considerations in preoperative history taking, intraoperative repair and suture selection, and postoperative counseling minimize the risk of postoperative dyschromia.

Abstract Rationale Postoperative pulmonary complications (PPCs) importantly contribute to postoperative morbidity and mortality, particularly for American Society of Anesthesiologists (ASA) physical status III patients. It remains unclear whether risk factors for PPCs depend on sex. We hypothesised that sex modifies the relationship between perioperative risk factors and PPCs in ASA III patients undergoing noncardiothoracic surgery with general anesthesia. Methods We performed a secondary analysis of prospective data from 1,202 ASA III patients undergoing non-cardiothoracic surgery. Data consisted of preoperative demographics, comorbidities, intraoperative physiology, medications, and procedure information. The primary outcome was a composite of PPCs by postoperative day 7. Mixed-effects linear models incorporated sex as main effect and interaction with covariates. Results Age, chronic obstructive pulmonary disease, upper abdominal surgery, surgical duration, and emergency surgery significantly increased the odds of ≥ 1 PPC by postoperative day 7. Male patients presented a higher rate of ≥ 3 PPCs, and mechanical ventilation was less protective in female patients. Yet, sex did not significantly modify the relationship between perioperative factors and the primary outcome (no p<0.05 for the interaction effect with sex). In the secondary analysis, gastroesophageal reflux disease affected atelectasis more strongly in male than female patients (relative odds-ratios for female versus male =0.27; 95% CI 0.13 to 0.57). Conclusions In ASA III patients undergoing non-cardiothoracic surgery with general anesthesia, perioperative factors are predominantly not significantly modified by sex in their relationship to PPCs. GERD’s association with atelectasis in male patients could be explored in future prospective studies as a target for reducing pulmonary complications. This abstract is funded by: NHLBI - UH3 HL140177

Imaging is important for evaluation and diagnosis of nail pathologic disorders, and knowledge of imaging protocols and characteristics supports informed treatment planning and effective monitoring of therapeutic outcomes in cutaneous and systemic disease contexts.

BACKGROUND Health care resource use, pollution, and greenhouse gas emissions are increasingly studied to balance quality patient care with environmental, social, and financial impacts. However, consolidated sustainability recommendations for Mohs micrographic surgery (MMS) remain unexplored. OBJECTIVE To assess current recommendations and studies on environmental sustainability in MMS. MATERIALS AND METHODS Following PRISMA-ScR guidelines, a literature review was conducted across PubMed, ScienceDirect, Scopus, Web of Science, and Cochrane databases from 2014 to 2024. English peer-reviewed studies using keywords “climate change,” “margin control,” “environment,” “sustainability,” “waste,” “resource,” “Mohs micrographic,” “Mohs,” and “micrographic” were included. Duplicates and conference abstracts were excluded. RESULTS Of 5,526 articles, nine met inclusion criteria after independent review. Recommendations included standardized surgical sets, limiting instruments to essentials, and redesigning procedure rooms to improve recycling access. Three articles found no significant difference in infection rates between sterile and nonsterile glove use. Other suggestions involved recycling plastics, using microtubules to reduce chromacoding dye waste by minimizing spillage and drying, and scheduling virtual preoperative visits to reduce travel emissions. Insurance reimbursement for virtual visits remains a limitation. CONCLUSION Restructuring surgical protocols and procedure room design encourages innovation and addresses workflow inefficiencies rooted in tradition rather than evidence, promoting sustainability in MMS.

Background: Tumor mutational burden (TMB) is an FDA-approved biomarker for immune checkpoint inhibitor (ICI) therapy. However, its predictive value varies among tumor types and molecular contexts. We investigated whether a very high TMB identifies a biologically distinct subset and whether a higher cutoff provides additional clinical insights beyond the conventional high TMB threshold. Methods: We analyzed 133 patients with advanced solid tumors and TMB ≥ 10 mutations/Mb (mut/Mb) who underwent tumor genomic profiling using a 523-gene DNA/RNA next-generation sequencing panel. Tumors were stratified into prespecified TMB categories: 10–20 mut/Mb (TMB-H) and >20 mut/Mb (TMB-VH). The clinical characteristics, ICI outcomes (in the treated subset), and pathway-level genomic features were compared between groups. Results: TMB-VH was observed in 42/133 (31.6%) patients and spanned more than 20 tumor types. MSI was markedly more prevalent in TMB-VH than in TMB-H tumors (38.1% vs. 2.2%; Fisher’s exact p = 8.9 × 10−8). Pathway-level comparisons did not identify statistically significant differences after false discovery rate correction (all q > 0.05), and the observed patterns were descriptive in nature. In the ICI-treated subset with complete follow-up, objective response did not differ according to the TMB group. Overall survival (OS) was also similar between groups, whether measured from metastatic diagnosis (log-rank p = 0.937) or from ICI initiation (log-rank p = 0.814), although OS was numerically longer in the TMB-VH group in both analyses without reaching statistical significance. Conclusions: In this cohort study, TMB-VH was strongly associated with MSI but not independently associated with improved ICI outcomes. Larger multicenter cohorts are needed to validate pathway-oriented patterns and clarify the clinical utility of extreme TMB thresholds across various histologies. Integrating the functional context (e.g., MSI status, gene-level context, and pathway-level features) with TMB magnitude may enable more robust, tumor-aware biomarker models for immunotherapy selection.

Oversight of Artificial Intelligence in Human Subjects Research (AI HSR) presents unique challenges. These challenges arise from both the non-linear and iterative nature of AI development, as well as from the way AI shifts risk from individual research subjects to larger populations affected by AI-driven decisions and data handling. Traditional Institutional Review Boards (IRBs) often struggle to keep pace with these changes, which can lead to gaps in risk assessment and delays in the review process. There is a growing need for transparent, repeatable methods to manage AI risk in healthcare. This paper introduces the Three-Stage Framework, a risk-based oversight model designed to align ethical and regulatory review with an AI project’s stage of maturity and potential human impact. By aligning the level and timing of IRB review with the types of risks present at each stage of AI system development, the framework supports appropriate regulatory pathways and documents expectations while maintaining effective protection of human subjects. Through gradual, stage-appropriate documentation, the approach supports responsible and adaptive innovation while preparing AI systems for safe and ethical use across biomedical, social, behavioral, and educational domains. This approach prepares AI systems for safe and ethical use, accelerates compliant research, and helps IRBs and institutions maintain trustworthiness while protecting human subjects.

Abstract Background Oxidative phosphorylation (OXPHOS) is a central function and a key indicator of mitochondrial fitness, yet studies in human tissue remain limited. Inclusion body myositis (IBM) is a progressive myopathy that lies at the intersection of aging, inflammation and mitochondrial dysfunction. We aimed to perform a comprehensive profiling of mitochondrial respiration in muscle tissue from patients with IBM. Methods A wide battery of complementary tests from RNA level to high-resolution respirometry on permeabilized muscle fibers was performed. The relationship between respiration, mitochondrial content, mitochondrial DNA (mtDNA) abnormalities and mitophagy was examined, along with the correlation with various clinical parameters to determine the clinical significance of the findings. Results The study included a total of 67 patients with IBM and 45 controls. IBM muscle tissue exhibited reduced maximal respiration per tissue weight in State 3 (high substrates, high ADP) and uncoupled state with decreased coupling efficiency and higher leak control ratios. When adjusting for citrate synthase reflecting mitochondrial content, males had decreased State 3 intrinsic respiration, whereas females had greater intrinsic respiration in leak states. Complex II control ratio strongly correlated with disease duration and severity only in females. IBM was associated with decreased RNA and protein expression of OXPHOS complexes. Complex I activity was decreased mainly in females. IBM samples exhibited lower maximal H 2 O 2 emission, accompanied by a higher total antioxidant capacity that correlated with disease duration in females. In IBM, there was decreased mtDNA content, and impaired mitophagy, both of which strongly correlated with respirometry measures and markers of disease severity, indicating these pathways are likely interconnected and of clinical significance. Conclusion IBM is characterized by multilevel impairments in mitochondrial coupling efficiency, revealing several potential therapeutic targets to improve mitochondrial fitness, while accounting for sex-specific differences.