Mohs Micrographic Surgery Is Equivalent to Nail Unit Excision or Amputation for Melanoma In Situ of the Nail Unit: A Systematic Review and Meta-Analysis.

BACKGROUND: Local recurrence (LR) rates of melanoma in situ (MIS) of the nail apparatus treated with different surgical modalities are unknown. OBJECTIVE: To evaluate the differences in LR rates of nail apparatus MIS treated with Mohs micrographic surgery (MMS) versus nail unit excision (NUE) versus amputation. METHODS: Studies of nail/subungual MIS treated with MMS, NUE, or amputation were identified through multiple literature databases, including PubMed, MEDLINE, Embase, Web of Science, and Cochrane Library. Pooled data were assessed through meta-analyses and Fisher exact test. RESULTS: Of 280 studies identified, 20 met inclusion criteria (7 comparative studies and 13 single-arm studies). Among the 7 comparative studies, the LR was 4.38% (5/114) after NUE and 2.94% (1/34) after amputation (odds ratio: 0.937; 95% CI: 0.237-3.703). In the 13 noncomparative studies, 23 patients underwent MMS (pooled LR estimate: 11.07%; 95% CI: 3.22%-31.81%) and 140 patients underwent NUE (pooled LR estimate:8.04%, 95% CI: 4.43%-14.16%). The difference in LR rate between MMS, NUE, and amputation was not statistically significant ( p = .578). CONCLUSION: Local recurrence of nail/subungual MIS in cases treated with MMS was not statistically different than in cases treated with NUE and was comparable to amputation. Further studies investigating the use of MMS for the treatment of nail/subungual MIS are warranted.

Efficacy and Safety of Anxiolytics in Mohs Micrographic Surgery: A Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Patient anxiety can complicate surgical outcomes by elevating blood pressure, increasing the need for postoperative pain management, and reducing overall patient satisfaction. Despite the use of anxiolytic medications in outpatient procedures, there is limited comparative evidence on the efficacy and safety of these agents in Mohs micrographic surgery. OBJECTIVE: To compare the effectiveness and safety of different preprocedural anxiolytic agents in Mohs surgery on perioperative patient anxiety and patient satisfaction. MATERIALS AND METHODS: A double-blinded, randomized, placebo-controlled trial was conducted of 6 different preprocedural anxiolytic agents (lorazepam, diazepam, alprazolam, gabapentin, pregabalin, and melatonin) in 350 patients undergoing Mohs surgery. Anxiety and vital signs were recorded. RESULTS: Diazepam demonstrated a statistically significant, sustained reduction in anxiety levels compared with placebo ( p = .03). Gabapentin significantly reduced early anxiety ( p = .02). Alprazolam showed a trend to early anxiety reduction ( p = .08). Lorazepam ( p = .73), pregabalin ( p = .53), and melatonin ( p = .24) failed to reduce patient anxiety compared with placebo at any time point. No anxiolytic significantly impacted any patient vital sign or cognition. CONCLUSION: Although short-acting benzodiazepines and gamma-aminobutyric acid medications may have transient anxiolytic effects, a single oral dose of 5 mg of diazepam can provide a sustained anxiolytic effect in Mohs surgery, with excellent patient safety.

Development of a core outcome set for basal cell carcinoma.

BACKGROUND: There is variation in the outcomes reported in clinical studies of basal cell carcinoma. This can prevent effective meta-analyses from answering important clinical questions. OBJECTIVE: To identify a recommended minimum set of core outcomes for basal cell carcinoma clinical trials. METHODS: Patient and professional Delphi process to cull a long list, culminating in a consensus meeting. To be provisionally accepted, outcomes needed to be deemed important (score, 7-9, with 9 being the maximum) by 70% of each stakeholder group. RESULTS: Two hundred thirty-five candidate outcomes identified via a systematic literature review and survey of key stakeholders were reduced to 74 that were rated by 100 health care professionals and patients in 2 Delphi rounds. Twenty-seven outcomes were provisionally accepted. The final core set of 5 agreed-upon outcomes after the consensus meeting included complete response; persistent or serious adverse events; recurrence-free survival; quality of life; and patient satisfaction, including cosmetic outcome. LIMITATIONS: English-speaking patients and professionals rated outcomes extracted from English language studies. CONCLUSION: A core outcome set for basal cell carcinoma has been developed. The use of relevant measures may improve the utility of clinical research and the quality of therapeutic guidance available to clinicians.

Quantification of Erythema Associated With Varying Suture Materials in Facial Surgery Repair: A Randomized Prospective Study.

BACKGROUND: A common concern among patients following Mohs micrographic surgery (MMS) is scar appearance and residual erythema. However, few studies have quantitatively compared scar erythema between different suture materials. OBJECTIVE: To quantify erythema intensity (EI) associated with use of percutaneous nylon, irradiated polyglactin-910 (IPG) and fast-absorbing gut (FG) sutures on facial sites. METHODS: After undergoing MMS, 210 patients were randomized to one of 2 groups. Patients in the first group (n = 105) had their defects repaired half with continuous IPG sutures and the other half with nylon sutures; the second group (n = 105) received IPG and FG sutures. Standardized photographs of scars were taken at 1 week, 2 months, and 6 months postoperatively and computer-assisted image analysis was used to quantify EI. RESULTS: The average EI was comparable between all 3 suture materials at 1 week, 2 months, and 6 months. From 1 week to 2 months, EI in nylon, IPG, and FG sutures decreased by 24.8%, 12.8%, and 17.9% (p < .05), respectively. There was no statistically significant difference in EI among suture types between 2 and 6 months. CONCLUSION: Erythema decreased significantly during early scar maturation in all groups and was comparable between all suture materials at 1 week, 2 months, and 6 months.

Viability and Cosmesis of Right Angle and Vertical Paramedian Forehead Flaps Are Equivalent: A Retrospective Quantitative Study.

BACKGROUND: Paramedian forehead flaps (PMFFs) are commonly used for reconstruction of nasal defects. The classic PMFF is vertically oriented while the modified PMFF is designed with a 90-degree angle. No study has compared outcomes between these PMFF designs. OBJECTIVE: To compare and quantify viability and cosmesis of 90-degree and vertical PMFF. METHODS: Retrospective chart review of 70 consecutive patients with a vertical or 90-degree PMFF design for nasal repairs after Mohs micrographic surgery (MMS). Cosmetic outcome was assessed on a 10-cm, 100-point, visual analog scale (VAS) by an independent observer using standardized 3-month postoperative photographs. Flap viability was assessed using standardized 3-week postoperative photographs. Descriptive statistics, t -test, and Mann-Whitney test were used for statistical analysis. RESULTS: Forty-eight patients were repaired with a vertical PMFF and 22 using the 90-degree PMFF. The mean defect area of vertical and 90-degree designs was equivalent (7.7 ± 4.0 cm 2 vs 8.1 ± 4.0 cm 2 , p = .70). There was no significant difference in cosmetic outcome (75.9 ± 9.4 vs 72.9 ± 6.8, p = .19) or flap viability (3.8% ± 11.6 vs 2.6% ± 7.9, p = .67) between vertical and 90-degree designs. CONCLUSION: Vertical and 90-degree PMFF designs for nasal repairs after MMS are equivalent in cosmetic outcome and viability.

Secondary Intention Healing Over Exposed Bone on the Scalp, Forehead, and Temple Following Mohs Micrographic Surgery.

BACKGROUND: Removal of skin cancers on the scalp, forehead, and temple can result in surgical defects with exposed bone. In such cases, reconstruction becomes challenging due to limited vascularity for flap or graft repair. OBJECTIVE: Demonstrate the usefulness of secondary intention healing of scalp, forehead, and temple defects over exposed bone. METHODS/MATERIALS: A retrospective case series of 41 patients who had Mohs Micrographic Surgery with post-surgical scalp, forehead, or temple defects involving exposed bone. These patients then underwent secondary intention healing. RESULTS: 90% of patients successfully healed. Average time to complete granulation was 92 days, and average time to full re-epithelialization was 186 days. Visual analog scale assessment of final scar quality resulted in 57% being good, 35% being fair, and 8% being poor. No patient had infection or other serious complication. Mean follow-up duration was 272 days. CONCLUSION: This case series shows the viability of secondary intention healing of scalp wounds over exposed bone. Study power was not adequate to predict time to complete healing based on defect size, or allow association of patient factors with the risk of nonhealing. Managing patient expectations, and emphasizing the importance of early occlusive wound care is paramount for healing success.

Interpolation Flaps in the Outpatient Mohs Surgery Setting: A Prospective Cohort Study of Patient Pain, Anxiety, and Satisfaction.

BACKGROUND: Staged interpolation flaps (SIFs) have historically been performed under general anesthesia by specialties outside of dermatologic surgery. However, SIFs performed under local anesthesia by dermatologic surgeons have shown lower or equal complication rates. OBJECTIVE: To date, no studies have evaluated pain, anxiety, satisfaction, and use of perioperative analgesics in patients undergoing SIFs in an outpatient setting under local anesthesia. METHODS/MATERIALS: This is a prospective cohort study of 39 patients who received Mohs micrographic surgery and subsequent SIF repair in an outpatient setting under local anesthesia. Pain, anxiety, and satisfaction scores were recorded using 100-point validated visual analog scales. Perioperative analgesic use was quantified. RESULTS: The defect size was ≥4 cm2 in 72% of patients; 41% had full-thickness (skin/cartilage/mucosa) defects. All pain and anxiety measures were minimal to mild. Pain scores ranged from highest (mean = 39 ± 4.1) on postoperative Day (POD) 1 to lowest (mean = 12.3 ± 2.0) on POD 7. Anxiety scores ranged from highest (mean = 42 ± 4.5) on POD 1 to lowest (mean = 18.5 ± 3.7) on POD 7. Perioperative patient satisfaction was high (mean = 95 ± 1.7). Postoperative narcotic analgesics were prescribed in 15% of patients. CONCLUSION: Staged interpolation flaps performed under local anesthesia in the outpatient setting are well tolerated with low pain and anxiety, high patient satisfaction, and minimal analgesic use.

Photographic assessment of postsurgical facial scars epidermally sutured with rapidly absorbable polyglactin 910 or nylon: A randomized clinical trial.

BACKGROUND: Surgeons use absorbable and nonabsorbable sutures for epidermal wound closure. No large, randomized studies have compared the effect of these suture types on facial scar appearance. OBJECTIVE: To assess postsurgical facial scar appearance using either rapidly absorbable polyglactin 910 or nylon for epidermal closure. METHODS: Randomized, blinded, split-scar clinical trial. A total of 105 patients with facial wounds resulting from Mohs micrographic surgery excisions were randomly assigned for epidermal closure with rapidly absorbable 5-0 polyglactin 910 (Vicryl Rapide) on one half of the repair and 5-0 nylon (Ethilon) on the other half. Two physicians (1 dermatologist and 1 plastic surgeon), unaware of the original suture location, examined photographs of each healed wound at 6 months after surgery and graded the appearance of each half of the scar using the visual analog scale, wound evaluation scale, and Stony Brook Scar Evaluation Scale. RESULTS: At 6 months, there was no significant difference in the combined mean (standard deviation) visual analog scale scores (83.1 [14.2] and 83.0 [13.7]), Stony Brook Scar Evaluation Scale scores (4.3 [0.9] and 4.4 [0.9]), or wound evaluation scale scores (5.3 [1.1] and 5.2 [1.1]) for rapidly absorbable polyglactin 910 versus nylon (P = .72, .57, and .21, respectively). LIMITATIONS: Single institution. CONCLUSIONS: Both rapidly absorbable polyglactin 910 and nylon sutures placed through the epidermis resulted in an equivalent photographic appearance of facial scars at 6 months after surgery.

Quantification of Erythema Associated With Continuous Versus Interrupted Nylon Sutures in Facial Surgery Repair: A Randomized Prospective Study.

BACKGROUND: Patients are often concerned about the cosmetic appearance of scars following Mohs micrographic surgery (MMS), including residual erythema. However, few studies have compared the cosmetic outcomes between different suturing techniques. OBJECTIVE: To compare the erythema intensity (EI) associated with interrupted sutures (IS) and continuous sutures (CS), and the degree of its reduction over time. MATERIALS AND METHODS: Mohs micrographic surgery patients were randomized to have half of their defect repaired with IS and the other half with CS. Postoperatively, subjects were assessed at 1 week, 2 months, and 6 months and close-up photographs of their scars were taken. Computer-assisted image analysis was utilized to quantify the EI in each half-scar. RESULTS: The average EI of IS was greater than that of CS by 9.3% at 1 week (p < .001) and 7.2% at 2 months (p < .021) but comparable at 6 months. These differences were clinically detectable, but EI differences resolved by 6 months in most cases. At 6 months, EI regressed by 33.5% in IS and 26.3% in CS. CONCLUSION: Continuous sutures are associated with less erythema during early scar maturation but are comparable to IS at 6 months. These results may guide the choice of suturing technique to improve early cosmetic outcomes and overall patient satisfaction.

Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial.

BACKGROUND: Vismodegib, a first-in-class Hedgehog-pathway inhibitor, is approved for use in adults with advanced basal-cell carcinoma. Patients with multiple basal-cell carcinomas, including those with basal-cell nevus (Gorlin) syndrome, need extended treatment. We assessed the safety and activity of two long-term intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas. METHODS: In this randomised, regimen-controlled, double-blind, phase 2 trial, we enrolled adult patients with multiple basal-cell carcinomas, including those with basal-cell nevus syndrome, who had one or more histopathologically confirmed and at least six clinically evident basal-cell carcinomas. From a centralised randomisation schedule accessed via an interactive voice or web-based response system, patients were randomly assigned (1:1) to treatment group A (150 mg oral vismodegib per day for 12 weeks, then three rounds of 8 weeks of placebo daily followed by 12 weeks of 150 mg vismodegib daily) or treatment group B (150 mg oral vismodegib per day for 24 weeks, then three rounds of 8 weeks of placebo daily followed by 8 weeks of 150 mg vismodegib daily). Treatment assignment was stratified by diagnosis of basal-cell nevus syndrome, geographical region, and immunosuppression status. The primary endpoint was percentage reduction from baseline in the number of clinically evident basal-cell carcinomas at week 73. The primary analysis was by intention to treat. The safety population included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01815840, and the study is ongoing. FINDINGS: Between April 30, 2013, and April 9, 2014, 229 patients were randomly assigned treatment, 116 in treatment group A and 113 in treatment group B. The mean number of basal-cell carcinoma lesions at week 73 was reduced from baseline by 62·7% (95% CI 53·0-72·3) in treatment group A and 54·0% (43·6-64·4) in treatment group B. 216 (95%) of 227 patients included in the safety analysis had at least one treatment-emergent adverse event deemed to be related to study treatment (107 [94%] of 114 in treatment group A and 109 [97%] of 113 in treatment group B). The most common grade 3 or worse treatment-related adverse events were muscle spasms (four [4%] patients in treatment group A vs 12 [11%] in treatment group B), increased blood creatine phosphokinase (one [1%] vs four [4%]), and hypophosphataemia (zero vs three [3%]). Serious treatment-emergent events were noted in 22 (19%) patients in treatment group A and 19 (17%) patients in treatment group B. Four (2%) patients died from adverse events; one (pulmonary embolism in treatment group A) was possibly related to treatment. INTERPRETATION: Both intermittent dosing schedules of vismodegib seemed to show good activity in long-term regimens in patients with multiple basal-cell carcinomas. Further study is warranted. FUNDING: F Hoffmann-La Roche.

Determinants and Timeline of Perioperative Anxiety in Mohs Surgery.

BACKGROUND: Patients undergoing Mohs micrographic surgery (MMS) exhibit anxiety relating to cancer cure or the expected cosmetic outcome. OBJECTIVE: To obtain quantitative measurements of perioperative cancer and cosmetic anxiety levels in first-time MMS patients. Parameters influencing anxiety and its natural course were assessed. METHODS: Prospective, single-blinded, questionnaire study of 173 patients undergoing MMS of the face. Anxiety levels were assessed using a visual analog scale preoperatively and postoperatively over 6 months. RESULTS: Mohs patients demonstrate a trend to greater or equal anxiety about cancer over cosmesis at all measured time points, but differences only reached statistical significance beginning 1 week postoperatively. Clinically relevant lowering of cancer anxiety levels is delayed until 3 months postoperatively. Cosmetic anxiety reaches a clinically relevant improvement by 1 week. The intuitive predictors of cosmetic anxiety, namely female gender and younger age, were quantitatively reinforced in this study. The predictor of cancer anxiety was the use of preoperative lorazepam. CONCLUSION: To maximize patient care, Mohs surgeons must be aware of covert patient anxieties and the parameters, which influence these anxieties. Identifying and anticipating the course of cancer- and cosmetic-related anxieties will reduce patient fears, improving their satisfaction with the MMS experience.

Real-time visualization of melanin granules in normal human skin using combined multiphoton and reflectance confocal microscopy.

BACKGROUND: Recent advances in biomedical optics have enabled dermal and epidermal components to be visualized at subcellular resolution and assessed noninvasively. Multiphoton microscopy (MPM) and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that have demonstrated promising results in imaging skin micromorphology, and which provide complementary information regarding skin components. This study assesses whether combined MPM/RCM can visualize intracellular and extracellular melanin granules in the epidermis and dermis of normal human skin. METHODS: We perform MPM and RCM imaging of in vivo and ex vivo skin in the infrared domain. The inherent three-dimensional optical sectioning capability of MPM/RCM is used to image high-contrast granular features across skin depths ranging from 50 to 90 µm. The optical images thus obtained were correlated with conventional histologic examination including melanin-specific staining of ex vivo specimens. RESULTS: MPM revealed highly fluorescent granular structures below the dermal-epidermal junction (DEJ) region. Histochemical staining also demonstrated melanin-containing granules that correlate well in size and location with the granular fluorescent structures observed in MPM. Furthermore, the MPM fluorescence excitation wavelength and RCM reflectance of cell culture-derived melanin were equivalent to those of the granules. CONCLUSION: This study suggests that MPM can noninvasively visualize and quantify subepidermal melanin in situ.

Continuous versus interrupted sutures for facial surgery repair: a randomized prospective study.

BACKGROUND: The cosmetic appearance of a facial scar is a concern for patients undergoing Mohs micrographic surgery (MMS). Although suturing technique may influence scar cosmesis, few studies have been published comparing suturing methods for MMS repair. OBJECTIVE: To compare the cosmetic appearance of facial MMS scars sutured with either continuous or interrupted percutaneous nylon sutures. MATERIALS AND METHODS: Patients with facial MMS defects were randomized to have half their scar sutured with interrupted 5-0 nylon stitches, whereas the other half of the scar was closed with running 5-0 nylon stitches. The appearance of each half of the scar was assessed at 1 week, 8 weeks, and 6 months by the principal investigator. Blinded photographic evaluation at 1 week and 6 months was completed by a plastic surgeon and general dermatologist. RESULTS: A total of 105 patients were entered into the trial, and 101 completed all time point assessments. There was no statistically significant difference in scar outcome using each of the 3 scar assessment scales, at any time point, for any assessor (blinded and nonblinded). CONCLUSION: Interrupted and continuous 5-0 nylon sutures result in an equivalent final cosmetic appearance of facial MMS scars. Given its advantages, running sutures may be the preferred closure technique for facial repair.

Tumor detection after inflammation or fibrosis on Mohs levels.

BACKGROUND: In Mohs micrographic surgery (MMS), many surgeons will take an additional level based solely on the presence of inflammation or fibrosis. OBJECTIVE: To determine the frequency with which this occurs and parameters predicting tumor discovery on successive levels. MATERIALS AND METHODS: A retrospective study was performed on 22,419 cases treated with MMS between 1996 and May 2011. The surgeons reviewed their own slides in cases where tumor was detected after a level was taken for inflammation or fibrosis. RESULTS: An additional level was taken for inflammation or fibrosis in 6,233 cases (27.8%), resulting in tumor detection in 121 cases (1.9%). Additional levels were taken for inflammation in 66.6% and fibrosis in 63.0%. Fourteen collision tumors were identified and were preceded by inflammation in 71% of cases. DISCUSSION: Factors that may predict the presence of tumor at subsequent levels include eccentrically placed or shallow first levels failing to completely encompass a previous surgical scar. The presence of dense inflammation may signal an adjacent collision tumor. CONCLUSION: Taking an additional Mohs level when dense inflammation or fibrosis is present may be warranted to ensure complete tumor removal.

Use of a patient and observer scar assessment scale to evaluate the V-Y advancement flap for reconstruction of medial cheek defects.

BACKGROUND: The V-Y advancement flap (VYF) is not commonly used to reconstruct defects located on the medial cheek. The quantitative assessment of VYF for this indication has not been reported. In evaluation of surgical scarring, the Patient and Observer Scar Assessment Scale (POSAS) has been validated for use in burn and breast surgery scars, but its usefulness in dermatologic surgery has not been determined. OBJECTIVE: To present our experience with the use of the POSAS to assess the success of VYF reconstruction for surgical defects on the medial cheek. METHODS AND MATERIALS: Fourteen patients with medium to large (>5 cm(2) ) medial cheek Mohs defects reconstructed using VYF were assessed. Final cosmetic and functional results were analyzed after a follow-up of 6 months to 2 years (mean follow-up 21 months) using the POSAS. RESULTS: Observers using the POSAS gave a mean score for VYF reconstructions of 9.1 ± 2.3 (5 represents normal skin, 50 represents worst imaginable scar). Patients using the POSAS gave a mean score for VYF reconstructions of 10 ± 4 (6 representing normal skin, 60 representing worst imaginable scar). CONCLUSION: VYF reconstruction of medium to large defects of the medial cheek is a useful option. The POSAS may be a helpful tool for evaluating reconstructive results in dermatologic surgery.

CXCR3/ligands are significantly involved in the tumorigenesis of basal cell carcinomas.

Basal cell carcinoma (BCC) is the most common skin malignancy encountered worldwide. We hypothesized that CXC chemokines, small cytokines involved in inducing directed leukocyte chemotaxis, could play a key role in the modulation of BCC growth. In this study, quantitative RT-PCR revealed that the chemokines CXCL9, 10, 11, and their receptor CXCR3 were significantly upregulated by an average 22.6-fold, 9.2-fold, 26.6-fold, and 4.9-fold, respectively in BCC tissue samples as compared with nonlesional skin epithelium. Immunohistochemistry analysis revealed that CXCR3, CXCL10, and CXCL11, but not CXCL9, colocalized with cytokeratin 17 (K17) in BCC keratinocytes. In addition, CXCR3 and its ligands were expressed in cells of the surrounding BCC stroma. The chemokines and K17 were also expressed in cultured human immortalized HaCaT keratinocytes. Exposure of HaCaT cells or primary BCC-derived cells to CXCL11 peptides in vitro significantly increased cell proliferation. In primary BCC-derived cell cultures, addition of CXCL11 progressively selected for K17+/CXCR3+ co-expressing cells over time. The expression of CXCR3 and its ligands in human BCC keratinocytes, the enhancement of keratinocyte cell proliferation by CXCL11, and the homogeneity of K17+ BCC cells in human BCC-isolated cell population supported by CXCR3/CXCL11 signaling all suggest that CXCR3 and its ligands may be important autocrine and/or paracrine signaling mediators in the tumorigenesis of BCC.

Skin care and hygiene among healthcare professionals during and after the SARS-CoV-2 pandemic.

The severe acute respiratory syndrome coronavirus 2 pandemic has necessitated enhanced protection against viral transmission among healthcare professionals, particularly relating to handwashing and personal protective equipment. Some of these requirements may persist for years to come. They bring associated concerns around skin hygiene and general care, with damage to the face and hands now a well-documented consequence among healthcare professionals. This review assesses optimal skin care during the severe acute respiratory syndrome coronavirus 2 pandemic and in the "new normal" that will follow, identifies current knowledge gaps, and provides practical advice for the clinical setting. Regular, systematic hand cleaning with soap and water or an alcohol-based hand rub (containing 60%-90% ethanol or isopropyl alcohol) remains essential, although the optimal quantity and duration is unclear. Gloves are a useful additional barrier; further studies are needed on preferred materials. Moisturization is typically helpful and has proven benefits in mitigating damage from frequent handwashing. It may be best practiced using an alcohol-based hand rub with added moisturizer and could be particularly important among individuals with pre-existing hand dermatoses, such as psoriasis and eczema. Face moisturization immediately prior to donning a mask, and the use of dressings under the mask to reduce friction, can be helpful dermatologically, but more work is required to prove that these actions do not affect seal integrity. Nonetheless, such measures could play a role in institutional plans for mitigating the dermatologic impact of transmission control measures as we exit the pandemic.

Core Outcome Set for Actinic Keratosis Clinical Trials.

Importance: Although various treatments have been found in clinical trials to be effective in treating actinic keratosis (AK), researchers often report different outcomes. Heterogeneous outcome reporting precludes the comparison of results across studies and impedes the synthesis of treatment effectiveness in systematic reviews. Objective: To establish an international core outcome set for all clinical studies on AK treatment using systematic literature review and a Delphi consensus process. Evidence Review: Survey study with a formal consensus process. The keywords actinic keratosis and treatment were searched in PubMed, Embase, CINAHL, and the Cochrane Library to identify English-language studies investigating AK treatments published between January 1, 1980, and July 13, 2015. Physician and patient stakeholders were nominated to participate in Delphi surveys by the Measurement of Priority Outcome Variables in Dermatologic Surgery Steering Committee members. All participants from the first round were invited to participate in the second round. Outcomes reported in randomized controlled clinical trials on AK treatment were rated via web-based e-Delphi consensus surveys. Stakeholders were asked to assess the relative importance of each outcome in 2 Delphi survey rounds. Outcomes were provisionally included, pending the final consensus conference, if at least 70% of patient or physician stakeholders rated the outcome as critically important in 1 or both Delphi rounds and the outcome received a mean score of 7.5 from either stakeholder group. Data analysis was performed from November 5, 2018, to February 27, 2019. Findings: A total of 516 outcomes were identified by reviewing the literature and surveying key stakeholder groups. After deduplication and combination of similar outcomes, 137 of the 516 outcomes were included in the Delphi surveys. Twenty-one physicians and 12 patients participated in round 1 of the eDelphi survey, with 17 physicians (81%) retained and 12 patients (100%) retained in round 2. Of the 137 candidate outcomes, 9 met a priori Delphi consensus criteria, and 6 were included in the final outcomes set after a consensus meeting: complete clearance of AKs, percentage of AKs cleared, severity of adverse events, patient perspective on effectiveness, patient-reported future treatment preference, and recurrence rate. It was recommended that treatment response be assessed at 2 to 4 months and recurrence at 6 to 12 months, with the AK rate of progression to cutaneous squamous cell carcinoma reported whenever long-term follow-up was possible. Conclusions and Relevance: Consensus was reached regarding a core outcome set for AK trials. Further research may help determine the specific outcome measures used to assess each of these outcomes.

Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis.

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non­follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self­renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.