Top 100 Most Cited Articles in Mohs Micrographic Surgery: A Bibliometric Analysis.

BACKGROUND: Bibliometric analysis is a scientific method that can derive insights into major publications' trends within a field. Currently, no bibliometric study has been conducted for Mohs micrographic surgery (MMS). OBJECTIVE: To characterize the most frequently cited articles in MMS. METHODS: Web of Science was used to identify the 100 most cited publications on MMS between 1970 and 2022. Articles were analyzed by title, authorship, institution, journal, year, citation frequency, originating country, funding, citation index, Altmetric score, impact factor, Eigenfactor score, and article influence score. RESULTS: Since January 2023, the top 100 articles had 9,096 total citations, ranging from 47 to 304. The top cited publication was "Mohs surgery is the treatment of choice for recurrent (previously treated) basal-cell carcinoma" in 1989. The top contributing organization was Harvard University (17%) and top contributing authors were Brodland, DJ (12%) and Zitelli, JA (11%). The year 2005 accounted for most of the articles (12%). Most articles were from the Journal of the American Academy of Dermatology (32%) and Dermatologic Surgery (27%). The United States contributed to 76% of the top articles. CONCLUSION: This bibliometric analysis offers researchers a detailed overview of important MMS publications and provides useful data into current findings steering MMS research and practice.

A prospective study evaluating the utility of a 2-mm biopsy margin for complete removal of histologically atypical (dysplastic) nevi.

BACKGROUND: Complete removal of individual dysplastic nevi (DN) is often accomplished by a second surgical procedure after the initial biopsy. The choice to perform the second procedure is strongly influenced by histopathologic margin status of the initial biopsy specimen. OBJECTIVE: To evaluate the clinical and histopathologic outcomes of in toto biopsy of DN using a predetermined margin of normal skin. METHODS: We conducted a prospective study of a saucerization method using a defined 2-mm margin in patients undergoing biopsy of a pigmented skin lesion. RESULTS: We performed 151 biopsies in 138 patients. Overall, 137 of 151 lesions subjected to biopsy (90.7%) were melanocytic: 86 DN (57.0%), 40 nevi without atypia (26.5%), and 11 melanomas (7.3%). Of 78 DN, 68 (87.2%) were removed with clear histopathologic margins (8 DN were excluded because of inadequate processing). There was no clinical evidence of recurrence at any of the biopsy sites that were simply observed (i.e., not re-excised) over a median of 16.9 months. LIMITATIONS: There were few biopsies performed on the face. CONCLUSIONS: The complete histopathologic removal of nearly 9 of 10 DN using a peripheral margin of 2 mm of normal skin and a depth at the dermis and subcutaneous fat junction has the potential to decrease second procedures at DN biopsy sites, thereby decreasing patient morbidity and saving health care dollars.

Successful treatment of two pediatric port wine stains in darker skin types using 595 nm laser.

BACKGROUND AND OBJECTIVE: Port wine stain (PWS) is a congenital vascular malformation of skin involving post-capillary venules, which commonly occurs on the face. While successful treatment has been reported with Caucasian, Hispanic, and Asian skin, physicians have battled treating these progressive lesions in patients of darker skin color, as the targeted chromophore (hemoglobin) shares a similar absorption coefficient as melanin. There are no reports of favorable outcomes in African-American children or adults. Although treatment in darker skin types has been previously discouraged we present a case series of patients of African descent with port wine stains treated using a pulsed-dye laser (Vbeam Perfecta, Candela Laser,Wayland, Mass) with significant improvement and no complications. STUDY DESIGN/MATERIAL AND METHODS: Presentation of two pediatric patients of African descent (skin types 4 and 5) ages 1 month and 4 years old seen and treated in our office using a pulsed-dye laser until resolution. Laser parameters were spot size 10 mm; fluence 7-8.25 J/cm2; wavelength 595 nm; pulse duration 1.5 Millisecond with dynamic cooling. RESULTS: Resolution of the port wine stain without complication. CONCLUSION: This early approach represents a new and safe therapeutic option for treating port wine stains in this patient population. To our knowledge, the successful use of pulsed dye laser for the treatment of port wine stain in patients of African descent without complications has not yet been reported.

Treatment of pigmentary disorders in patients with skin of color with a novel 755 nm picosecond, Q-switched ruby, and Q-switched Nd:YAG nanosecond lasers: A retrospective photographic review.

BACKGROUND AND OBJECTIVES: Laser procedures in skin of color (SOC) patients are challenging due to the increased risk of dyspigmentation and scarring. A novel 755 nm alexandrite picosecond laser has demonstrated effectiveness for tattoo removal and treatment of acne scars. No studies to date have evaluated its applications in pigmentary disorders. The purpose of this retrospective study was to evaluate the safety profile and efficacy of the picosecond alexandrite laser compared to the current standard treatment, Q-switched ruby and neodynium (Nd):YAG nanosecond lasers, for pigmentary disorders in SOC patients. STUDY DESIGN/MATERIALS AND METHODS: A retrospective photographic and chart evaluation of seventy 755 nm alexandrite picosecond, ninety-two Q-switched frequency doubled 532 nm and 1,064 nm Nd:YAG nanosecond, and forty-seven Q-switched 694 nm ruby nanosecond laser treatments, in forty-two subjects of Fitzpatrick skin types III-VI was conducted in a single laser specialty center. The picosecond laser was a research prototype device. Treatment efficacy was assessed by two blinded physician evaluators, using a visual analog scale for percentage of pigmentary clearance in standard photographs. Subject assessment of efficacy, satisfaction, and adverse events was performed using a questionnaire survey. RESULTS: The most common pigmentary disorder treated was Nevus of Ota (38.1%), followed by solar lentigines (23.8%). Other pigmentary disorders included post-inflammatory hyperpigmentation, congenital nevus, café au lait macule, dermal melanocytosis, Nevus of Ito, and Becker's nevus. Clinical efficacy of the Q-switched nanosecond lasers and picosecond laser treatments were comparable for lesions treated on the face with a mean visual analog score of 2.57 and 2.44, respectively, corresponding to approximately 50% pigmentary clearance. Subject questionnaires were completed in 58.8% of the picosecond subjects and 52.0% of the Q-switched subjects. Eighty four percent of subjects receiving Q-switched nanosecond laser treatments and 50% of the subjects receiving alexandrite 755 nm picosecond laser treatments felt satisfied to completely satisfied. Side effects observed in subjects treated with the alexandrite 755 nm picosecond laser were similar to those commonly observed and reported with the nanosecond Q-switched technology. All side effects were temporary, resolving within one month, and no long-term complications were noted. All patients who were very satisfied with their picosecond laser treatment for Nevus of Ota noted a delayed improvement only after 3 months. CONCLUSION: The 755 nm alexandrite picosecond, 694 nm ruby, 532 nm, and 1064 nm neodynium:YAG nanosecond lasers appear to be safe and effective modalities for removal of pigmentary disorders in skin of color patients with no long-term complications if used appropriately. This study demonstrates the potential of the 755 nm alexandrite picosecond laser in further clinical applications beyond tattoo removal. While the Q-switched lasers were effective, promising results were also observed using an early version of the novel picosecond laser for the removal of pigmentary lesions in SOC patients. As we continue to improve our understanding of the 755 nm picosecond laser, this device may prove to be a safe and effective alternative to the Q-switched lasers for the treatment of facial pigmented lesions in patients with skin of color.

Idiopathic scleredema.

Scleredema, which also is known as scleredemaadultorum of Buschke, is an uncommonsclerodermiform condition that is characterizedby progressive thickening and hardening of theskin due to excessive dermal mucin and collagendeposition. The clinical course is variable, andprogression of disease may lead to functionalimpairment with limitations in mobility. The etiologyand pathogenesis are unknown although severalwell-known associations include streptococcalinfection; diabetes mellitus, particularly withmetabolic syndrome; and monoclonal gammopathy.We present a case of scleredema in a 52-year-oldman with no identifiable associated condition,who experienced improvemement with UVBphototherapy.

Cowden syndrome presenting with trichilemmomas.

Cowden syndrome (CS) is a genetic cancerpredisposition syndrome that is associated withgermline mutations in the phosphate and tensinhomologue deleted on chromosome ten (PTEN)tumor suppressor gene. It is characterizedby the formation of benign and malignanttumors. Characteristic benign tumors includetrichilemmommas, acral keratoses, mucocutaneousneuromas, and oral papillomas. The most commonmalignant condition include breast, thyroid, andendometrial cancers. We present a case of a30-year-old woman with CS, who initially presentedwith trichilemmomas that were misdiagnosed ascomedonal acne. Recognition of the presentingfeatures of CS is important to ensure proper referral,management, and treatment for these patients.

Netherton syndrome with ichthyosis linearis circumflexa and trichorrhexis invaginatum.

Netherton syndrome is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, trichorrhexis invaginata, and atopic diathesis. Ichthyosis presents at birth with erythroderma and subsequently evolves into ichthyosis linearis circumflexa; hair shaft abnormalities tend to present later. The disorder is caused by loss-of-function mutations in the SPINK5 (serine protease inhibitor Kazal-type 5) gene that encodes LEKTI (lympho-epithelial Kazal-type related inhibitor), which is a protease inhibitor that counteracts epidermal proteases involved in desquamation. Use of topical medications is limited by potential for systemic absorption and toxicity in the setting of a defective skin barrier. Therapeutic options include topical glucocorticoids and retinoids, oral retinoids, and narrowband ultraviolet B phototherapy. Topical tacrolimus has been shown to be efficacious and may be used safely with careful laboratory monitoring.

Cranial fasciitis.

A 26-year-old man presented with an 18-month history of a subcutaneous mass on his forehead that occurred shortly after being struck by a blunt object. Histopathologic examination showed a proliferation of bland spindle cells and a collagenous stroma that was consistent with cranial fasciitis. Cranial fasciitis, which is a variant of nodular fasciitis, is a benign fibroblastic neoplasm that overlies the skull and often is associated with trauma. Although its rapid onset may give the clinical impression of a malignant condition, cranial fasciitis typically is cured by simple excision without further sequelae.

Automated detection of erythema migrans and other confounding skin lesions via deep learning.

Lyme disease can lead to neurological, cardiac, and rheumatologic complications when untreated. Timely recognition of the erythema migrans rash of acute Lyme disease by patients and clinicians is crucial to early diagnosis and treatment. Our objective in this study was to develop deep learning approaches using deep convolutional neural networks for detecting acute Lyme disease from erythema migrans images of varying quality and acquisition conditions. This study used a cross-sectional dataset of images to train a model employing a deep convolutional neural network to perform classification of erythema migrans versus other skin conditions including tinea corporis and herpes zoster, and normal, non-pathogenic skin. Evaluation of the machine's ability to classify skin types was also performed on a validation set of images. Machine performance for detecting erythema migrans was further tested against a panel of non-medical humans. Online, publicly available images of both erythema migrans and non-Lyme confounding skin lesions were mined, and combined with erythema migrans images from an ongoing, longitudinal study of participants with acute Lyme disease enrolled in 2016 and 2017 who were recruited from primary and urgent care centers. The final dataset had 1834 images, including 1718 expert clinician-curated online images from unknown individuals with erythema migrans, tinea corporis, herpes zoster, and normal skin. It also included 116 images taken of 63 research participants from the Mid-Atlantic region. Two clinicians carefully annotated all lesion images. A convenience sample of 7 non-medically-trained humans were used as a panel to compare against machine performance. We calculated several performance metrics, including accuracy and Kappa (characterizing agreement with gold standard), as well as a receiver operating characteristic curve and associated area under the curve. For detecting erythema migrans, the machine had an accuracy (95% confidence interval error margin) of 86.53% (2.70), ROCAUC of 0.9510 (0.0171) and Kappa of 0.7143. Our results suggested substantial agreement between machine and clinician criterion standard. Comparison of machine with non-medical expert human performance indicated that the machine almost always exceeded acceptable specificity, and could operate with higher sensitivity. This could have benefits for prescreening prior to physician referral, earlier treatment, and reductions in morbidity.

Development of a melanoma risk prediction model incorporating MC1R genotype and indoor tanning exposure: impact of mole phenotype on model performance.

BACKGROUND: Identifying individuals at increased risk for melanoma could potentially improve public health through targeted surveillance and early detection. Studies have separately demonstrated significant associations between melanoma risk, melanocortin receptor (MC1R) polymorphisms, and indoor ultraviolet light (UV) exposure. Existing melanoma risk prediction models do not include these factors; therefore, we investigated their potential to improve the performance of a risk model. METHODS: Using 875 melanoma cases and 765 controls from the population-based Minnesota Skin Health Study we compared the predictive ability of a clinical melanoma risk model (Model A) to an enhanced model (Model F) using receiver operating characteristic (ROC) curves. Model A used self-reported conventional risk factors including mole phenotype categorized as "none", "few", "some" or "many" moles. Model F added MC1R genotype and measures of indoor and outdoor UV exposure to Model A. We also assessed the predictive ability of these models in subgroups stratified by mole phenotype (e.g. nevus-resistant ("none" and "few" moles) and nevus-prone ("some" and "many" moles)). RESULTS: Model A (the reference model) yielded an area under the ROC curve (AUC) of 0.72 (95% CI = 0.69, 0.74). Model F was improved with an AUC = 0.74 (95% CI = 0.71-0.76, p<0.01). We also observed substantial variations in the AUCs of Models A & F when examined in the nevus-prone and nevus-resistant subgroups. CONCLUSIONS: These results demonstrate that adding genotypic information and environmental exposure data can increase the predictive ability of a clinical melanoma risk model, especially among nevus-prone individuals.

Intra- and inter-tumor heterogeneity of BRAF(V600E))mutations in primary and metastatic melanoma.

The rationale for using small molecule inhibitors of oncogenic proteins as cancer therapies depends, at least in part, on the assumption that metastatic tumors are primarily clonal with respect to mutant oncogene. With the emergence of BRAF(V600E) as a therapeutic target, we investigated intra- and inter-tumor heterogeneity in melanoma using detection of the BRAF(V600E) mutation as a marker of clonality. BRAF mutant-specific PCR (MS-PCR) and conventional sequencing were performed on 112 tumors from 73 patients, including patients with matched primary and metastatic specimens (n = 18). Nineteen patients had tissues available from multiple metastatic sites. Mutations were detected in 36/112 (32%) melanomas using conventional sequencing, and 85/112 (76%) using MS-PCR. The better sensitivity of the MS-PCR to detect the mutant BRAF(V600E) allele was not due to the presence of contaminating normal tissue, suggesting that the tumor was comprised of subclones of differing BRAF genotypes. To determine if tumor subclones were present in individual primary melanomas, we performed laser microdissection and mutation detection via sequencing and BRAF(V600E)-specific SNaPshot analysis in 9 cases. Six of these cases demonstrated differing proportions of BRAF(V600E)and BRAF(wild-type) cells in distinct microdissected regions within individual tumors. Additional analyses of multiple metastatic samples from individual patients using the highly sensitive MS-PCR without microdissection revealed that 5/19 (26%) patients had metastases that were discordant for the BRAF(V600E) mutation. In conclusion, we used highly sensitive BRAF mutation detection methods and observed substantial evidence for heterogeneity of the BRAF(V600E) mutation within individual melanoma tumor specimens, and among multiple specimens from individual patients. Given the varied clinical responses of patients to BRAF inhibitor therapy, these data suggest that additional studies to determine possible associations between clinical outcomes and intra- and inter-tumor heterogeneity could prove fruitful.

Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity.

Recruitment of signaling molecules to the cytoplasmic domains of the CD3 subunits of the T-cell receptor (TCR) is crucial for early T-cell activation. These transient associations either do or do not require tyrosine phosphorylation of CD3 immune tyrosine activation motifs (ITAMs). Here we show that the non-ITAM-requiring adaptor protein Nck forms a complex with an atypical PxxDY motif of the CD3epsilon tail, which encompasses Tyr166 within the ITAM and a TCR endocytosis signal. As suggested by the structure of the complex, we find that Nck binding inhibits phosphorylation of the CD3epsilon ITAM by Fyn and Lck kinases in vitro. Moreover, the CD3epsilon-Nck interaction downregulates TCR surface expression upon physiological stimulation in mouse primary lymph node cells. This indicates that Nck performs an important regulatory function in T lymphocytes by inhibiting ITAM phosphorylation and/or removing cell surface TCR via CD3epsilon interaction.

1-13C amino acid selective labeling in a 2H15N background for NMR studies of large proteins.

Isotope labeling by residue type (LBRT) has long been an important tool for resonance assignments at the limit where other approaches, such as triple-resonance experiments or NOESY methods do not succeed in yielding complete assignments. While LBRT has become less important for small proteins it can be the method of last resort for completing assignments of the most challenging protein systems. Here we present an approach where LBRT is achieved by adding protonated (14)N amino acids that are (13)C labeled at the carbonyl position to a medium for uniform deuteration and (15)N labeling. This has three important benefits over conventional (15)N LBRT in a deuterated back ground: (1) selective TROSY-HNCO cross peaks can be observed with high sensitivity for amino-acid pairs connected by the labeling, and the amide proton of the residue following the (13)C labeled amino acid is very sharp since its alpha position is deuterated, (2) the (13)C label at the carbonyl position is less prone to scrambling than the (15)N at the alpha-amino position, and (3) the peaks for the 1-(13)C labeled amino acids can be identified easily from the large intensity reduction in the (1)H-(15)N TROSY-HSQC spectrum for some residues that do not significantly scramble nitrogens, such as alanine and tyrosine. This approach is cost effective and has been successfully applied to proteins larger than 40 kDa.