Comparison of Digital Pathology and Light Microscopy Among Dermatology Residents: A Reappraisal Following Practice Changes.

BACKGROUND: Following transition to digital pathology for primary diagnosis at our institution, dermatology residents have reduced exposure to light microscopy. This study compares resident competency with light microscopy versus digital pathology following practice changes. METHODS: Twenty-one dermatology residents were administered a dermatopathology examination composed of 32 diagnoses evaluated using digital slides and 32 with light microscopy. Case difficulty was graded and balanced between modalities. Diagnostic accuracy was measured using the number of correct diagnoses for each modality. Participants were surveyed regarding their experience and preferences. RESULTS: Diagnostic accuracy was higher with digital pathology than light microscopy (22/32 vs. 18/32, P < 0.001). Diagnostic accuracy with digital pathology increased with years of training, but accuracy with light microscopy did not. Residents with previous light microscopy experience achieved an average score of 19/32 on glass, as compared with 10/32 for those without experience (P = 0.039). Digital pathology was preferred over light microscopy (18/21, 85.7%). CONCLUSIONS: Trainees had better diagnostic proficiency with digital pathology and preferred this modality. Most practices at this time continue to use light microscopy. Therefore, we need to maintain proficiency in microscopy during training while concurrently preparing trainees for a digital future.

Postoperative Complications After Interpolated Flap Repair for Mohs Defects of the Nose: A Multicenter Prospective Cohort Study.

BACKGROUND: Dermatologists perform most interpolated flaps after skin cancer resection. Prospective, multicenter data on complications after interpolated flap repair in this setting are limited. OBJECTIVE: To determine the rate of physician-reported complications after interpolated flap repair of the nose. METHODS: Multicenter, prospective cohort study of 169 patients undergoing 2-stage interpolated flap repair of post-Mohs nasal defects. Frequency of bleeding, infection, dehiscence, necrosis, hospitalization, and death in the 30 days after flap placement and flap takedown are reported. RESULTS: Patients experienced 23 complications after flap placement (13.61%) and 6 complications after flap takedown (3.55%) that were related to the surgical procedure. The most frequent complication after flap placement was bleeding (9, 5.33%, 95% confidence interval [CI]: 2.83%-9.82%). The most frequent complication after flap takedown was infection (5, 2.96%, 95% CI: 1.27%-6.74%). There was one hospitalization related to an adverse reaction to antibiotics. There were no deaths. CONCLUSION: Most complications after interpolated flap repair for post-Mohs defects of the nose are minor and are associated with flap placement. Interpolated flap repair for post-Mohs defects can be performed safely in the outpatient setting under local anesthesia.

Safety of Periocular Mohs Reconstruction: A Two-Center Retrospective Study.

BACKGROUND: Repair of periocular defects poses unique functional and aesthetic challenges. Data on the safety of periocular repairs by Mohs surgeons are limited. OBJECTIVE: Analyze the frequency and types of postreconstruction complications encountered with periocular repairs performed by Mohs surgeons, identify risk factors associated with complications, and enumerate interventions for complications encountered. MATERIALS AND METHODS: An institutional review board-approved retrospective study on periocular repairs performed by Mohs surgeons at 2 academic institutions between 07 2013 and 06 2016. Patients undergoing periocular Mohs surgery were identified via billing codes. Patient demographics and surgery details were recorded. Follow-up visit notes were reviewed for postoperative complications and interventions performed. RESULTS: Two hundred ten cases were included in the analysis. The most common locations for postreconstruction complications were the medial canthus (57%) and lower eyelid (37%). The complications identified included medial canthal webbing (4.3%), hypertrophic scarring (4.3%), ectropion (1.9%), infection (1.4%), pincushioning (1.4%), and epiphora (1.0%). The most common postoperative intervention was intralesional triamcinolone. Scar revision was performed in 2.4% of all cases. CONCLUSION: Periocular repairs performed by Mohs surgeons have a similar safety profile as repairs performed by oculoplastic surgeons.

Postoperative Infections in Dermatologic Surgery: The Role of Wound Cultures.

BACKGROUND: Dermatologic surgery is associated with low postoperative infection rates, averaging from approximately 1% to 4.25%. Often, postoperative infections are treated empirically based on clinical diagnosis of infection, given it can take 48 to 72 hours for a wound culture to identify a pathogen. OBJECTIVE: We aimed to evaluate the efficacy of empiric antibiotics in dermatologic surgery postoperative infections and if wound cultures change postoperative antibiotic therapy. METHODS: A 7-center, retrospective analysis of postoperative infections, with culture data, in dermatologic surgery patients was performed. RESULTS: Of 91 cases of clinically diagnosed postoperative infection, 82.4% (n = 75) were successfully treated with empiric oral antibiotics (95% confidence interval [0.73-0.89], p < .0001). In 16 (17.6%) cases, initial empiric antibiotics were unsuccessful, and wound culture results altered antibiotic therapy in 9 cases (9.9%) with 6 (6.6%) of these cases requiring additional coverage for methicillin-resistant Staphylococcus aureus (MRSA). CONCLUSION: Empiric antibiotic treatment is usually appropriate for patients with postoperative surgical-site infections with wound cultures altering antibiotic management in a minority of cases. When empiric antibiotics fail, lack of MRSA coverage is usually the cause; therefore, providers should be aware of local MRSA prevalence and susceptibilities.

Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining for atypical intraepidermal melanocytic proliferation.

BACKGROUND: The efficacy of Mohs micrographic surgery (MMS) for atypical intraepidermal melanocytic proliferation (AIMP) is unknown. OBJECTIVE: To ascertain the frequency of diagnostic change to melanoma (upstaging) and the frequency of local recurrence after MMS for AIMP. A secondary outcome was the frequency of subclinical spread (defined as the requirement for >1 stage of MMS to achieve tumor-free margins). METHODS: Retrospective, cross-sectional study of 223 AIMP (with 92.4% located on the head, neck, hand, foot, or pretibial leg) patients treated with MMS with melanoma antigen recognized by T cells 1 (MART-1) immunostaining. RESULTS: Upstaging to unequivocal melanoma in situ or invasive melanoma was identified in 18.8% (42/223) of all AIMP patients. The local recurrence rate was 0% (0/223) with a mean follow-up time of 2.7 years (998 days). Subclinical spread was present in 23.8% (53/223) of AIMP patients. LIMITATIONS: Single site, retrospective design, observational study, lack of objective criteria to diagnose AIMP. CONCLUSION: MMS with MART-1 immunostaining achieves excellent local control of specialty site AIMP and permits definitive removal of subclinical spread before reconstruction. The central debulking excision should be evaluated with formalin-fixed paraffin-embedded section staining, since a significant percentage of AIMP are reclassified as melanoma in situ or invasive melanoma.

Patients prioritize local recurrence risk over other attributes for surgical treatment of facial melanomas-Results of a stated preference survey and choice-based conjoint analysis.

BACKGROUND: Surgical treatment options for facial melanomas include conventional excision with postoperative margin assessment, Mohs micrographic surgery (MMS) with immunostains (MMS-I), and slow MMS. Patient preferences for these surgical options have not been studied. OBJECTIVES: To evaluate patient preferences for surgical treatment of facial melanoma and to determine how patients value the relative importance of different surgical attributes. METHODS: Participants completed a 2-part study consisting of a stated preference survey and a choice-based conjoint analysis experiment. RESULTS: Patients overwhelmingly (94.3%) rated local recurrence risk as very important and ranked it as the most important attribute of surgical treatment for facial melanoma. Via choice-based conjoint analysis, patients ranked the following surgical attributes from highest to lowest in importance: local recurrence rate, out-of-pocket cost, chance of second surgical visit, timing of reconstruction, travel time, and time in office for the procedure. Consistent with their prioritization of low local recurrence rates, more than 73% of respondents selected MMS-I or slow MMS as their preferred treatment option for a facial melanoma. LIMITATIONS: Data were obtained from a single health system. CONCLUSION: Patients prefer surgical treatment options that minimize risk for local recurrence. Logistics for travel and treatment have less influence on patient preferences. Most survey participants chose MMS-I to maximize local cure and convenience of care.

Patient Preferences for the Treatment of Basal Cell Carcinoma: A Mapping Review of Discrete Choice Experiments.

BACKGROUND: Treatment options for skin cancer differ in several attributes including efficacy, convenience, cost, scarring, and side effects. Discrete choice experiments (DCEs) provide insight into how patients value the attributes of their treatment options. OBJECTIVE: To review published DCE data on skin cancer treatment. METHODS: PubMed database was systematically searched using predefined keyword combinations for articles pertaining to skin cancer treatment and DCEs through October 2017. Three hundred seventy unique article titles were evaluated, and titles that did not mention skin cancer treatment were excluded leaving 44 studies. Abstracts of 44 studies were examined, and studies that used DCEs to query preference for skin cancer treatment were included in this mapping review. RESULTS: Six articles that used DCEs to query patient preference for skin cancer treatment were reviewed. All DCE studies identified focused on basal cell carcinoma. CONCLUSION: Discrete choice experiments are a rigorous method of eliciting patient preference for skin cancer surgery. Recurrence was the most important attribute in 4 of the 6 studies reviewed. Appearance was the most important attribute in 1 study and the second most important in 3 studies. Comparisons between studies are limited by the heterogeneity of the treatment attributes and levels included in DCEs.

Semi-automated quantification of C9orf72 expansion size reveals inverse correlation between hexanucleotide repeat number and disease duration in frontotemporal degeneration.

We investigated whether chromosome 9 open reading frame 72 hexanucleotide repeat expansion (C9orf72 expansion) size in peripheral DNA was associated with clinical differences in frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) linked to C9orf72 repeat expansion mutations. A novel quantification workflow was developed to measure C9orf72 expansion size by Southern blot densitometry in a cross-sectional cohort of C9orf72 expansion carriers with FTD (n = 39), ALS (n = 33), both (n = 35), or who are unaffected (n = 21). Multivariate linear regressions were performed to assess whether C9orf72 expansion size from peripheral DNA was associated with clinical phenotype, age of disease onset, disease duration and age at death. Mode values of C9orf72 expansion size were significantly shorter in FTD compared to ALS (p = 0.0001) but were not associated with age at onset in either FTD or ALS. A multivariate regression model correcting for patient's age at DNA collection and disease phenotype revealed that C9orf72 expansion size is significantly associated with shorter disease duration (p = 0.0107) for individuals with FTD, but not with ALS. Despite considerable somatic instability of the C9orf72 expansion, semi-automated expansion size measurements demonstrated an inverse relationship between C9orf72 expansion size and disease duration in patients with FTD. Our finding suggests that C9orf72 repeat size may be a molecular disease modifier in FTD linked to hexanucleotide repeat expansion.

Hypermethylation of repeat expanded C9orf72 is a clinical and molecular disease modifier.

C9orf72 promoter hypermethylation inhibits the accumulation of pathologies which have been postulated to be neurotoxic. We tested here whether C9orf72 hypermethylation is associated with prolonged disease in C9orf72 mutation carriers. C9orf72 methylation was quantified from brain or blood using methylation-sensitive restriction enzyme digest-qPCR in a cross-sectional cohort of 118 C9orf72 repeat expansion carriers and 19 non-carrier family members. Multivariate regression models were used to determine whether C9orf72 hypermethylation was associated with age at onset, disease duration, age at death, or hexanucleotide repeat expansion size. Permutation analysis was performed to determine whether C9orf72 methylation is heritable. We observed a high correlation between C9orf72 methylation across tissues including cerebellum, frontal cortex, spinal cord and peripheral blood. While C9orf72 methylation was not significantly different between ALS and FTD and did not predict age at onset, brain and blood C9orf72 hypermethylation was associated with later age at death in FTD (brain: ß = 0.18, p = 0.006; blood: ß = 0.15, p < 0.001), and blood C9orf72 hypermethylation was associated with longer disease duration in FTD (ß = 0.03, p = 0.007). Furthermore, C9orf72 hypermethylation was associated with smaller hexanucleotide repeat length (ß = -16.69, p = 0.033). Finally, analysis of pedigrees with multiple mutation carriers demonstrated a significant association between C9orf72 methylation and family relatedness (p < 0.0001). C9orf72 hypermethylation is associated with prolonged disease in C9orf72 repeat expansion carriers with FTD. The attenuated clinical phenotype associated with C9orf72 hypermethylation suggests that slower clinical progression in FTD is associated with reduced expression of mutant C9orf72. These results support the hypothesis that expression of the hexanucleotide repeat expansion is associated with a toxic gain of function.

C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD.

Hexanucleotide repeat expansions of C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal degeneration. The mutation is associated with reduced C9orf72 expression and the accumulation of potentially toxic RNA and protein aggregates. CpG methylation is known to protect the genome against unstable DNA elements and to stably silence inappropriate gene expression. Using bisulfite cloning and restriction enzyme-based methylation assays on DNA from human brain and peripheral blood, we observed CpG hypermethylation involving the C9orf72 promoter in cis to the repeat expansion mutation in approximately one-third of C9orf72 repeat expansion mutation carriers. Promoter hypermethylation of mutant C9orf72 was associated with transcriptional silencing of C9orf72 in patient-derived lymphoblast cell lines, resulting in reduced accumulation of intronic C9orf72 RNA and reduced numbers of RNA foci. Furthermore, demethylation of mutant C9orf72 with 5-aza-deoxycytidine resulted in increased vulnerability of mutant cells to oxidative and autophagic stress. Promoter hypermethylation of repeat expansion carriers was also associated with reduced accumulation of RNA foci and dipeptide repeat protein aggregates in human brains. These results indicate that C9orf72 promoter hypermethylation prevents downstream molecular aberrations associated with the hexanucleotide repeat expansion, suggesting that epigenetic silencing of the mutant C9orf72 allele may represent a protective counter-regulatory response to hexanucleotide repeat expansion.

Patient-Reported Nasal Function and Appearance After Interpolation Flap Repair Following Skin Cancer Resection: A Multicenter Prospective Cohort Study.

Objective: Among patients undergoing two-stage interpolated flap repair of nasal defects, nasal function, and appearance before surgery and at 16 weeks after flap takedown were compared using the Nasal Appearance and Function Evaluation Questionnaire (NAFEQ). Design: Multicenter prospective cohort study. Methods: Adult patients with a nasal skin cancer anticipated to require two-stage interpolation flap repair completed the NAFEQ before surgery, at 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Results: One hundred sixty-nine patients were enrolled, with 138 patients completing both presurgical and 16-week post-takedown NAFEQs. Overall NAFEQ score increased by 1.09 points (1.91% improvement, confidence interval [95% CI -0.34 to 2.53]). NAFEQ functional subscale increased by 0.72 points (2.58% increase; 95% CI [0.10-1.35]) and appearance subscale increased by 0.37 points (1.28% improvement, 95% CI [-0.65 to 1.39]). Conclusion: At 16 weeks after flap takedown, patients' perceptions of their nasal function and appearance are similar to or slightly improved when compared with their presurgical assessments.

Interdisciplinary Management of Extramammary Paget's Disease Using Mohs Micrographic Surgery With Frozen Section Cytokeratin-7 Immunostains.

OBJECTIVE: To describe local recurrence rates and patient-reported outcomes when Mohs micrographic surgery with cytokeratin-7 immunostains (MMS-CK7) is included in the interdisciplinary management of extramammary Paget's disease (EMPD) METHODS: A retrospective study was conducted of EMPD treated with MMS-CK7 as part of an interdisciplinary team at an academic medical center between 2009 and 2016. Local recurrence rates and patient-reported outcomes were determined by record review and patient surveys. RESULTS: Twenty tumors in 19 patients were treated using MMS-CK7. After MMS-CK7 defined clear microscopic margins, 75% (15/20) of tumors underwent excision or reconstruction by a surgical colleague. Internal malignancy screening was performed by multiple specialties in 17 patients, with 1 associated malignancy of prostate cancer detected. No local recurrence was detected with a mean follow-up of 75.2 months. Most patients were satisfied with appearance (18/19, 95%) and function (16/19, 84%) after surgery. CONCLUSION: Interdisciplinary teams that include MMS-CK7 can treat EMPD with low local recurrence rates, high patient satisfaction, and thorough internal malignancy screening.

A novel form of oxytocin in New World monkeys.

Oxytocin is widely believed to be present and structurally identical in all placental mammals. Here, we report that multiple species of New World monkeys possess a novel form of oxytocin, [P8] oxytocin. This mutation arises from a substitution of a leucine to a proline in amino acid position 8. Further analysis of this mutation in Saimiri sciureus (squirrel monkey) indicates that [P8] oxytocin is transcribed and translated properly. This mutation is specific to oxytocin, as the peptide sequence for arginine vasopressin, a structurally related nonapeptide, is unaltered. These findings dispel the notion that all placental mammals possess a 'universal' oxytocin sequence, and highlight the need for research on the functional significance of this novel nonapeptide in New World monkeys.

Patient Quality of Life After Interpolated Flap Repair of Nasal Mohs Surgery Defects: A Multicenter Prospective Cohort Study.

IMPORTANCE: Single-center studies have shown that patients report better skin cancer-specific quality of life (QOL) after Mohs micrographic surgery (MMS), but it is unclear whether this improved QOL applies to patients after MMS and complex reconstruction in cosmetically sensitive areas. OBJECTIVE: To evaluate patient QOL after MMS and interpolation flap reconstruction for patients with nasal skin cancers. DESIGN, SETTING AND PARTICIPANTS: This multicenter prospective survey study used the Skin Cancer Index (SCI), a validated, 15-question QOL questionnaire administered at 4 time points: before MMS, 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Patients age 18 years or older with a nasal skin cancer who presented for MMS and were anticipated to undergo 2-stage interpolated flap repair by a Mohs surgeon were recruited from August 9, 2018, to February 2, 2020, at 8 outpatient MMS locations across the United States, including both academic centers and private practices. MAIN OUTCOMES AND MEASURES: Mean difference in overall SCI score before MMS vs 16 weeks after flap takedown. RESULTS: A total of 169 patients (92 men [54.4%]; mean [SD] age, 67.7 [11.4] years) were enrolled, with 147 patients (75 men [51.0%]; mean [SD] age, 67.8 [11.7] years) completing SCI surveys both before MMS and 16 weeks after flap takedown. Total SCI scores improved significantly 16 weeks after flap takedown compared with pre-MMS scores, increasing by a mean of 13% (increase of 7.11 points; 95% CI, 5.48-8.76; P < .001). All 3 SCI subscale scores (emotion, appearance, and social) improved significantly (emotion subscale, increase of 3.27 points; 95% CI, 2.35-4.18; P < .001; appearance subscale, increase of 1.65 points; 95% CI, 1.12-2.18; P < .001; and social subscale, increase of 2.10 points; 95% CI, 1.55-2.84; P < .001) 16 weeks after flap takedown compared with pre-MMS. CONCLUSIONS AND RELEVANCE: Removal of a nasal skin cancer and repair of the resulting defect can be distressing for patients. However, this cohort study suggests that physicians referring patients for MMS can be reassured that their patient's QOL will improve on average after surgery, even when a complex reconstruction is required.

A New Injury Prevention Target: Summer Hair Braids.

Scald injuries caused by hair braiding have become increasingly common in our pediatric burn center's African-American population. This injury mechanism has received little attention in the medical literature. To guide prevention, the present study aims to characterize this novel mechanism of injury and identify patterns underlying its frequency. A retrospective cohort analysis was performed on all cases of scald injury due to hair braiding in African-American girls treated at our burn center from 2000 to 2016. Data were gathered from the patient's medical records to determine demographics, details of the injury, and treatment rendered. Patterns of injury frequency were identified and statistically analyzed. Thirty-four patients suffered scald injuries associated with hair braiding. The mean patient age was 8.4 years (SD ± 5 years). The majority of injuries (90%) occurred in the home. The frequency of injuries significantly increased starting in the year 2012, rising from less than 3% to more than 10% of evaluated injuries in African-American girls (P = .0015). Injuries were significantly more frequent in summer months. Injuries resulted in considerable usage of medical resources, including ambulance transport, hospital admission, clinic visits, prolonged wound care, and surgery. Complications developed in 41% of injured children; the most frequent complication was scarring. Pediatric scald injuries caused by braiding practices are morbid, have recently become increasingly frequent, tend to occur in the summer, and may be related to a new do-it-yourself style trend among African-American girls.