Faculty Bibliography

Opportunities to improve the clinical management of skin disease are being created by advances in genomic medicine. Large-scale sequencing increasingly challenges notions about single-gene disorders. It is now apparent that monogenic etiologies make appreciable contributions to the population burden of disease and that they are underrecognized in clinical practice. A genetic diagnosis informs on molecular pathology and may direct targeted treatments and tailored prevention strategies for patients and family members. It also generates knowledge about disease pathogenesis and management that is relevant to patients without rare pathogenic variants. Inborn errors of immunity are a large class of monogenic etiologies that have been well-studied and contribute to the population burden of inflammatory diseases. To further delineate the contributions of inborn errors of immunity to the pathogenesis of skin disease, we performed a set of analyses that identified 316 inborn errors of immunity associated with skin pathologies, including common skin diseases. These data suggest that clinical sequencing is underutilized in dermatology. We next use these data to derive a network that illuminates the molecular relationships of these disorders and suggests an underlying etiological organization to immune-mediated skin disease. Our results motivate the further development of a molecularly derived and data-driven reorganization of clinical diagnoses of skin disease.

BACKGROUND:Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS:A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS:Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS:This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

While power is often defined and operationalized as control or influence over others, alternative conceptualizations define power as the ability to meet various fundamental needs. We argue that this conceptualization may better capture how marginalized minority group members understand their group's power or powerlessness. However, there is little research examining how people themselves construe group-based power. The present study, therefore, used qualitative inquiry to examine perceived ingroup power among Asian Americans, an underrepresented racial minority group with an ambivalent power status in society. Reflexive thematic analysis of 25 interviews illustrated the relevance of Prilleltensky's (J. Community Psychol., 36, 2008, 116) psychopolitical conceptualization of power. Specifically, we identified eight themes that reflect various context-specific construals of power as oppression, wellness and liberation. Additionally, the findings suggest the need to consider intragroup heterogeneity in power and to situate how power is understood in the given sociopolitical, structural context.

BACKGROUND:The COVID-19 pandemic compelled older adults to engage with technology to a greater extent given emergent public health observance and home-sheltering restrictions in the United States. This study examined subjective experiences of technology use among older adults as a result of unforeseen and widespread public health guidance catalyzing their use of technology differently, more often, or in new ways. OBJECTIVE:This study aimed to explore whether older adults scoring higher on the Unified Theory of Acceptance and Use of Technology questionnaire fared better in aspects of technology use, and reported better subjective experiences, in comparison with those scoring lower. METHODS:A qualitative study using prevalence and thematic analyses of data from 18 older adults (mean age 79 years) in 2 groups: 9 scoring higher and 9 scoring lower on the Unified Theory of Acceptance and Use of Technology questionnaire. RESULTS:Older adults were fairly competent technology users across both higher- and lower-scoring groups. The higher-scoring group noted greater use of technology in terms of telehealth and getting groceries and household items. Cognitive difficulty was described only among the lower-scoring group; they used technology less to get groceries and household items and to obtain health information. Qualitative themes depict the role of habit in technology use, enthusiasm about technology buttressed by the protective role of technology, challenges in technology use, and getting help regardless of technology mastery. CONCLUSIONS:Whereas the pandemic compelled older adults to alter or increase technology use, it did not change their global outlook on technology use. Older adults' prepandemic habits of technology use and available help influenced the degree to which they made use of technology during the COVID-19 pandemic.

INTRODUCTION:This systematic review aims to evaluate the use of machine learning and artificial intelligence in hernia surgery. METHODS:The PRISMA guidelines were followed throughout this systematic review. The ROBINS-I and Rob 2 tools were used to perform qualitative assessment of all studies included in this review. Recommendations were then summarized for the following pre-defined key items: protocol, research question, search strategy, study eligibility, data extraction, study design, risk of bias, publication bias, and statistical analysis. RESULTS:A total of 13 articles were ultimately included for this review, describing the use of machine learning and deep learning for hernia surgery. All studies were published from 2020 to 2023. Articles varied regarding the population studied, type of machine learning or Deep Learning Model (DLM) used, and hernia type. Of the thirteen included studies, all included either inguinal, ventral, or incisional hernias. Four studies evaluated recognition of surgical steps during inguinal hernia repair videos. Two studies predicted outcomes using image-based DMLs. Seven studies developed and validated deep learning algorithms to predict outcomes and identify factors associated with postoperative complications. CONCLUSION:The use of ML for abdominal wall reconstruction has been shown to be a promising tool for predicting outcomes and identifying factors that could lead to postoperative complications.

BACKGROUND:Lipid metabolism has essential roles in skin barrier formation and the regulation of skin inflammation. Lipid homeostasis regulates skin melanogenesis, although the underlying mechanism remains largely unknown. Sterol regulatory element binding protein 1 (SREBP-1) is a key transcription factor essential for cellular lipid metabolism. Loss-of-function variants in SREBF1 are responsible for autosomal-dominant ichthyosis follicularis, alopecia and photophobia syndrome, emphasizing the significance of lipid homeostasis in skin keratinization. OBJECTIVES/OBJECTIVE:To identify the genetic basis of a new entity featuring diffuse skin hyperpigmentation with congenital cataracts, and to unravel the underlying mechanism for the pathogenesis of the SREBF1 variant. METHODS:Whole-exome sequencing was performed to identify underlying genetic variants. Quantitative polymerase chain reaction, Western blot and immunofluorescence staining were used to assess the expression and the subcellular localization of the SREBF1 variant. The transcriptional activity of mutant SREBP-1 was determined by a luciferase reporter assay. A transgenic zebrafish model was constructed. RESULTS:Two unrelated patients presented with generalized skin hyperpigmentation with skin xerosis, congenital cataracts and extracutaneous symptoms. We identified a de novo nonsense variant c.1289C>A (p.Ser430*) in SREBF1 in both patients. The variant encoded a truncated protein that showed preferential nucleus localization, in contrast to wild-type SREBP-1 which - in sterol-sufficient conditions - is mainly localized in the cytoplasm. The luciferase reporter assay revealed that the p.Ser430* mutant exhibited enhanced transcriptional activity. Cultured patient primary melanocytes showed increased melanin synthesis vs. those from healthy controls. At 35 days postfertilization, the p.Ser430* transgenic zebrafish model exhibited more black spots, along with upregulated expression of melanogenic genes. CONCLUSIONS:We demonstrated that a gain-of-function variant of SREBF1 causes a previously undescribed disorder characterized by generalized skin hyperpigmentation and congenital cataracts. Our study reveals the involvement of SREBP-1 in melanogenesis and lens development, and paves the way for the development of novel therapeutic targets for skin dyspigmentation or cataracts.

Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)-a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single-cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated but also found that the expression of molecules targeted therapeutically, namely PSMA, STEAP1, STEAP2, TROP2, CEACAM5, and DLL3, varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to current and future antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types.

BACKGROUND:Sleeve gastrectomy (SG) is the most commonly performed metabolic and bariatric surgery (MBS) procedure. Technical considerations related to the performance of SG are well established and reported in the literature but not in relation to robotic-assisted (RA) SG. We report the results of the first modified Delphi consensus-building exercise addressing technical considerations of RA da Vinci (dV) SG. OBJECTIVES/OBJECTIVE:Develop best practices for the performance of robotic-assisted da Vinci sleeve gastrectomy. SETTING/METHODS:Survey based consensus statement. METHODS:A consensus building committee (CBC) was created comprising 10 experts in the field of RA surgery and MBS based on strict selection criteria. The CBC developed 49 consensus statements which were then shared with 240 experts in RA surgery. Our stopping criterion was stability in responses (≤15%). The consensus cut point was 70%. RESULTS:The overall response rate was 49%. In the first round of voting, there was consensus agreement on 25 statements (51%), consensus disagreement on 14 (28%), and no consensus on the remaining statements (21%). In the second round of voting, we reached agreement on 3 additional statements. Experts recommended the use of the number of pauses generated by the stapler to guide choice of staple height (91.2%) and to upsize the staple height when using buttressing (92%). There was also consensus (81.4%) that the use of the closed staple height of 1.00 mm (white) is acceptable and that stapling of the antrum using a 1.5-mm staple (blue load) is also acceptable (73%). CONCLUSIONS:Collective expert opinion structured through a modified Delphi consensus statement presents a practical guide for surgeons interested in performing dV-SG.

OBJECTIVE:Determine the effects of differential maxillary expansion on nasal width in patients with unilateral cleft lip and alveolus with or without cleft of the secondary palate (UCLA ± P). DESIGN/METHODS:Retrospective radiographic study. SETTING/METHODS:Institutional. PARTICIPANTS/METHODS:Forty patients with UCLA ± P who had alveolar bone grafting (ABG) between 2015 and 2020 and available preexpansion and postexpansion cone beam computed tomography (CBCT) scans. Twenty patients with UCLA ± P who underwent ABG without expansion were included as controls. MAIN OUTCOME MEASURE/METHODS:Percent change in width at the nasal pyriform, inferior turbinates, and alar base on cleft and noncleft sides. RESULTS: ≤ 0.001) in the expansion group. There was good to excellent intra-rater and inter-rater agreement for measurements. CONCLUSION/CONCLUSIONS:Patients with UCLA ± P who undergo differential maxillary expansion before ABG exhibit greater nasal widening on the cleft side.