Wound Healing After Fractional Skin Harvesting.

BACKGROUND: Autologous fractional full-thickness skin grafting is a method of harvesting full-thickness skin with reduced donor site morbidity compared with conventional skin grafting. OBJECTIVE: To demonstrate that full-thickness skin microbiopsies can be harvested with minimal scarring or complications. MATERIALS AND METHODS: In a nonrandomized, self-controlled, pilot trial, subjects ( n = 8) underwent tissue harvesting of full-thickness skin columns of 200, 400, 500, 600, 800 µm, 1, and 2 mm diameters. The extent of scarring was measured by using the Patient and Observer Scar Assessment Scale and blinded evaluation of photographs at 6 weeks postprocedure. Pain visual analog scale (VAS) and side effects were recorded. RESULTS: When present, scars were first observed after 2 to 4 weeks, much more often for wounds >400 µm ( p < .001). Blinded dermatologists increasingly identified clinical scarring on photographs with larger harvested microcolumn diameters ( p < .001). Median VAS pain score was 0 (range 0-4). All subjects rated the procedure safe and tolerable. CONCLUSION: Harvesting full-thickness skin microcolumns is well-tolerated over a wide range of column diameters. At diameters of less than 500 µm, side effects including scarring are minimal.

Validating Techniques for Measurement of Cutaneous Neurofibromas: Recommendations for Clinical Trials.

OBJECTIVE: To assess the reliability and variability of digital calipers, 3D photography, and high-frequency ultrasound (HFUS) for measurement of cutaneous neurofibromas (cNF) in patients with neurofibromatosis type 1 (NF1). BACKGROUND: cNF affect virtually all patients with NF1 and are a major source of morbidity. Reliable techniques for measuring cNF are needed to develop therapies for these tumors. METHODS: Adults with NF1 were recruited. For each participant, 6 cNF were assessed independently by 3 different examiners at 5 different time points using digital calipers, 3D photography, and HFUS. The intraclass correlation coefficient (ICC) was used to assess intrarater and interrater reliability of linear and volumetric measurements for each technique, with ICC values >0.90 defined as excellent reliability. The coefficient of variation (CV) was used to estimate the minimal detectable difference (MDD) for each technique. RESULTS: Fifty-seven cNF across 10 participants were evaluated. The ICC for image acquisition and measurement was >0.97 within and across examiners for HFUS and 3D photography. ICC for digital calipers was 0.62-0.88. CV varied by measurement tool, linear vs volumetric measurement, and tumor size. CONCLUSIONS: HFUS and 3D photography demonstrate excellent reliability whereas digital calipers have good to excellent reliability in measuring cNF. The MDD for each technique was used to create tables of proposed thresholds for investigators to use as guides for clinical trials focused on cNF size. These criteria should be updated as the performance of these end points is evaluated.

A strategy for empowering clinicians and increasing innovation: the Magic Wand Initiative.

Clinicians play a critical role in recognizing, initiating, and adopting innovative solutions to clinical problems. Increasing clinician involvement in problem-based innovation will help identify and solve unmet medical needs. The overall objective of our program was to increase clinician involvement in problem-based innovation. We pioneered and piloted the "Magic Wand" Initiative (MWI) at Massachusetts General Hospital Department of Dermatology, by inviting clinical faculty to voluntarily participate in problem-driven innovation. The primary outcome was the number of unmet clinical needs identified and pursued by clinicians, who were 'activated' to initiate problem-based innovation. Other objectives were to enhance clinician-to-clinician dialogue and to develop specific strategic framework for clinician-led, problem-driven research. This pilot MWI was started in 2013 with an announcement at dermatology faculty meeting inviting all clinical faculty to participate on volunteer basis. Academic dermatologists were the main participants in this program. They also contacted, collaborated and worked with research faculty, industry experts and lawyers. Out of 30 unmet needs identified by clinicians participating in MWI, eight are actively being pursued by clinicians. Three of those cases presented here have achieved publications, grant funding, prototype devices and product for patient use. In conclusion, MWI is an innovative approach that educates and equips clinician to identify and solve problems and engages them as leaders in their healthcare ecosystem. MWI has achieved concrete measurable success, affirming that if clinicians are empowered and supported to identify and solve existing unmet medical problems, new and innovative solutions can be invented to improve patient care.

Construction and validation of UV-C decontamination cabinets for filtering facepiece respirators.

We present evidence-based design principles for three different UV-C based decontamination systems for N95 filtering facepiece respirators (FFRs) within the context of the SARS-CoV-2 outbreak of 2019-2020. The approaches used here were created with consideration for the needs of low- and middle-income countries (LMICs) and other under-resourced facilities. As such, a particular emphasis is placed on providing cost-effective solutions that can be implemented in short order using generally available components and subsystems. We discuss three optical designs for decontamination chambers, describe experiments verifying design parameters, validate the efficacy of the decontamination for two commonly used N95 FFRs (3M, #1860 and Gerson #1730), and run mechanical and filtration tests that support FFR reuse for at least five decontamination cycles.

Evaluation of Safety and Efficacy of Laser Hair Removal With the Long-Pulsed 755 nm Wavelength Laser: A Two-Center Study With 948 Patients.

BACKGROUND AND OBJECTIVES: Laser hair removal is the most common laser therapy and the third most commonly performed procedure with more than one million treatments in United States in 2016. This retrospective study was conducted to assess long-term efficacy and safety of the 755 nm laser for hair removal. STUDY DESIGN/MATERIALS AND METHODS: Nearly, 3,606 laser treatments were performed with the long-pulsed 755 nm wavelength laser equipped with an epidermal cooling device between 1997 and 2005 and were followed till 2013. Standardized assessments were conducted by two treating physicians and patients at two follow-up intervals. At first follow-up, clearance was assessed by two physicians and clearance and satisfaction by patients. At the second follow-up, patients were assessed if hair clearance sustained compared with the first follow-up. RESULTS: Nine hundred and forty-eight patients with Fitzpatrick skin types I-IV were treated with a total of 3,606 laser treatments in this study. The mean age at the beginning of the study was 35 years (±11), 95.1% of patients were female (n = 902) and 4.9% male (n = 46). Five hundred and seventy-four patients received a minimum of three treatments and an average of 5.31 (3-16) treatments on axilla, back, bikini, breast, abdomen, face, lower extremity, or upper extremity region. First, follow-up was conducted 3.9 (±1.5) years after the final laser treatment. Seventy-four percent of these patients received 75-100% clearance as reported by the physician and 48% clearance as reported by the patient. Fifty-two percent of patients reported slower hair growth and 42% change in hair texture. Ninety percent of patients treated on axilla, 82% treated on the bikini area, and 79% treated on lower extremities experienced 75% or more clearance after three treatments. Facial, as well as breast and abdomen treatments, only showed a 66% and 62%, respectively, after three treatments. For these locations, five and more treatments were needed to achieve a quote of 79% (face) or 80% (breast and abdomen) for a 75-100% clearance. Upper extremity and back treatments did not have enough physician ratings to draw conclusions. Long-term adverse events were minimal and were all located on the face (one patient scar, four patients herpes infection). Second follow-up of 173 patients was conducted after 11.5 years (±2.0) and 87.9% of patients reported that their improvement sustained. CONCLUSIONS: The long-pulsed 755 nm alexandrite laser is a safe and efficacious treatment for the reduction of unwanted body hair with permanent results and high patient satisfaction. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

A crosslinked polymer skin barrier film for moderate to severe atopic dermatitis: A pilot study in adults.

BACKGROUND: Occlusive treatments are a mainstay in atopic dermatitis (AD) management but may not be well tolerated or lack compliance. A comfortable, semiocclusive, artificial skin barrier that is well tolerated, provides protection, and reduces water loss is needed. OBJECTIVE: To evaluate the potential tolerability and therapeutic benefits of a crosslinked polymer layer (XPL) in adults with AD. METHODS: A single-center, open-label pilot study was conducted involving 10 subjects with moderate to severe AD. Subjects applied XPL up to twice daily for 30 days on a selected treatment area. Investigator's Global Assessment, clinical signs of eczema, and pruritus were assessed on days 1, 3, 5, 15, and 30. Film durability and patient satisfaction were also evaluated. RESULTS: Investigator's Global Assessment scores improved from moderate to severe at baseline to clear to almost clear in 8 of 9 patients at day 30. Pruritus improved from trace to severe itching (baseline) to all subjects having trace to no itching at day 30. There was 1 adverse event of mild exudative dermatitis. LIMITATIONS: The study was limited by small sample size, open-label design, and lack of control. CONCLUSION: XPL may be an effective adjuvant in AD treatment. A larger study with a control group is warranted.

Significant skin-tightening by closure of fractional ablative laser holes.

BACKGROUND AND OBJECTIVE: Ablative fractional laser treatment uses thousands of very small laser beam wounds to damage a fraction of the skin, which stimulates tissue remodeling. Each open micro-wound heals without scarring, but the amount of skin tightening achieved is limited. This animal study was performed to test the hypothesis that immediate temporary closure of fractional laser wounds could increase skin tightening after fractional ablative laser treatment. MATERIALS AND METHODS: Four adult swine were used for the study; 98 square test sites (3 × 3 cm) were tattooed on the abdomen and flanks of each pig. An ablative fractional Erbium:YAG laser (Sciton Profile, Sciton Inc, Palo Alto, CA) was used to treat the test areas. A laser micro-spot fluence of 375 J/cm2 was delivered in 150-250 microseconds pulses, resulting in an array of ablation channels extending 1.5 mm deep into the skin, with a spot size of 250 µm, with 10% treatment density. Immediately following laser exposure the resulting holes were closed using a stretched elastic adhesive dressing, which, when applied, recoiled and compressed the diameter of the ablation holes. The compressive dressings were removed after 7 days. This procedure was compared to removing the same amount of skin (10%) mechanically by specially designed 19 gauge coring needles, as well as to the same laser and coring methods without compression closure. Area and shape of test sites were measured by digital photography before and 28 days after treatment. Data analysis included compensation for animal growth, as measured by increase in the area of the untreated control sites. RESULTS: All treated and control sites healed within a week, without scarring evident at 28 days. Laser treatment combined with compressive wound closure caused significant shrinkage at 28 days compared with untreated control sites. The treated skin area was reduced by 11.5% (P = 0.0001). Needle coring with wound closure produced similar, significant shrinkage (8%, P < 0.0021), whereas laser and needle coring treatment without closure did not result in significant area reduction (P = 0.1289) compared with untreated control sites. CONCLUSION: Significant skin tightening can be achieved by immediate temporary non-invasive wound closure after short pulse Er:YAG fractional ablative laser treatment, as well as after mechanically removing skin with a coring needle. This approach may improve skin tightening after ablative laser treatments. Further clinical studies are necessary to confirm successful application in humans. Lasers Surg. Med. 50:64-69, 2018. © 2017 Wiley Periodicals, Inc.

An elastic second skin.

We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly curing at the skin interface without the need for heat- or light-mediated activation. In a pilot human study, we examined the performance of a prototype XPL that has a tensile modulus matching normal skin responses at low strain (<40%), and that withstands elongations exceeding 250%, elastically recoiling with minimal strain-energy loss on repeated deformation. The application of XPL to the herniated lower eyelid fat pads of 12 subjects resulted in an average 2-grade decrease in herniation appearance in a 5-point severity scale. The XPL platform may offer advanced solutions to compromised skin barrier function, pharmaceutical delivery and wound dressings.

Immediate skin responses to laser and light treatments: Warning endpoints: How to avoid side effects.

Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

Immediate skin responses to laser and light treatments: Therapeutic endpoints: How to obtain efficacy.

Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints.

Micro-fractional, directional skin tightening: A porcine model.

BACKGROUND AND OBJECTIVE: Skin changes are among the most visible signs of aging. Fractional ablative lasers improve skin quality by making small skin wounds that heal rapidly without scarring. While they improve skin texture and discoloration, there is minimal effect on skin laxity. This study was performed to assess skin shrinkage performed by removing multiple small full-thickness skin columns with coring needles combined with wound closure. MATERIALS AND METHODS: In 5 swine 116 squares (3 cm(2) ) were demarcated for treatment and control sites. In treatment sites 10% of the skin was removed by full-thickness skin coring needles (19 gauge) and afterwards closed and compressed with an elastic adhesive dressing. This procedure was compared to puncturing the skin with standard hypodermic needles (without tissue removal) and subsequent closure with compressive dressing. Area and shape of sites were measured before and 28 days after treatment. RESULTS: Test and control sites healed within a week without scarring. Coring with wound closure caused significant shrinkage after 28 days. The treated skin area was reduced by 9% (P < 0.0001) and the direction of shrinkage was influenced by the direction of wound closure. Coring without wound closure and puncturing the skin without tissue removal produced an insignificant 3% decrease in area. CONCLUSION: Significant minimally invasive skin tightening in a preferred direction can be achieved by removing skin with coring needles followed by wound closure. The direction of shrinkage is influenced by the direction of micro-hole closure, irrespective of the skin tension lines. This approach may allow reshaping the skin in a desired direction without scarring.

Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities: A One-Year Follow-up Study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AK) is lower on the distal extremities compared with head and neck areas. A recent pilot study demonstrated increased efficacy of ALA PDT when the skin is warmed during ALA incubation. Prolonged clearance rates on the heated extremity were noted in 3 subjects that were evaluated after the study ended. The aim of this study was to evaluate the longevity of clearance rates after temperature-modulated PDT for the treatment of AKs on the extremities. MATERIALS AND METHODS: A total of 18 subjects (20 pairs of extremities) with at least 10 AKs on the upper or lower extremities were enrolled in the single-center study. Twenty percent ALA was applied to both extremities and heated during the 1-hour incubation period, followed by exposure to 10 J/cm 417-nm blue light. Lesions were photographed, counted, and templated at baseline, 1 week, and 3, 6, 9, and 12 months after treatment. RESULTS: A total of 17 subjects completed the 1-year study. The total number of lesions counted at baseline was 724 Grade 1 and 2 AKs (median 15 on each extremity). The lesion count at 3 and 12 months was 70 (9.6%) and 72 (9.9%), respectively. Grade 3 AKs did not resolve with treatment. The median baseline temperature of the treated extremities was 31.6°C. The median maximum temperature during the 1-hour incubation period was 41.2°C. The median clearance at 3 months was 90% and the same was maintained at 12 months. No new AK lesions formed in the treated areas within the 12-month follow-up period. CONCLUSION: Warming the skin after application of ALA is well tolerated, does not increase side effects, and increases the long-term efficacy of PDT for the treatment of AKs. The authors suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice.

Acne Treatment Based on Selective Photothermolysis of Sebaceous Follicles with Topically Delivered Light-Absorbing Gold Microparticles.

The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10-50 J cm(-2), 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1-2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris.

Temperature-modulated photodynamic therapy for the treatment of actinic keratosis on the extremities: a pilot study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AKs) is lower on the distal extremities compared with the head and neck areas. The strong temperature dependence of porphyrin synthesis in biologic tissue suggests that heating skin during incubation may improve the efficacy of PDT, particularly in areas where biologic temperatures are naturally lower. The aim of this study was to evaluate the efficacy and tolerability of temperature-modulated PDT for the treatment of AKs on the extremities. METHODS: In this IRB-approved, single-center study, the upper or lower extremities of 20 subjects were treated with 20% ALA under occlusion, followed by 10 J/cm, 417-nm blue light. One of the 2 extremities treated was heated during the 1-hour incubation. Outcome measures included lesion counts, tolerability, and global improvement at baseline, 1 week, and 2 and 6 months after treatment. RESULTS: The median temperatures of the heated and control sides were 38.8°C and 29.4°C, respectively. The median clearance for the heated side was significantly greater than the control side at 2 and 6 months (p < .0001). Typical PDT side effects were greater on the heated side compared with the control yet were well tolerated by all subjects. CONCLUSION: Warming the skin during incubation of ALA seems to improve the efficacy of PDT in the treatment of AKs on the extremities and is well tolerated when heat application is controlled within the limits of safety.

Pretreatment with ablative fractional laser changes kinetics and biodistribution of topical 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL).

BACKGROUND AND OBJECTIVES: 5-Aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) are porphyrin precursors used topically for photodynamic therapy (PDT). Previous studies have established that ablative fractional laser (AFXL) increases topical drug uptake. We evaluated kinetics and biodistribution of ALA- and MAL-induced porphyrins on intact and disrupted skin due to AFXL. MATERIALS AND METHODS: Two Yorkshire swine were exposed to CO2 AFXL (10.6 µm, 1,850 µm ablation depth) and subsequent topical application of ALA and MAL cream formulations (20%, weight/weight). Porphyrin fluorescence was quantified by digital fluorescence photography (30, 90, and 180 minutes) and fluorescence microscopy at specific skin depths (180 minutes). RESULTS: Porphyrins gradually formed over time, differently on intact and AFXL-disrupted skin. On intact skin (no AFXL), fluorescence photography showed that MAL initially induced higher fluorescence than ALA (t = 30 minutes MAL 21.1 vs. ALA 7.7 au, t = 90 minutes MAL 39.0 vs. ALA 26.6 (P < 0.009)) but reached similar intensities for long-term applications (t = 180 minutes MAL 56.6 vs. ALA 52 au, P = ns). AFXL considerably enhanced porphyrin fluorescence from both photosensitizers (P < 0.05). On AFXL-exposed skin, MAL expressed higher fluorescence than ALA for short-term application (t = 30 minutes, AFXL-MAL 26.4 vs. AFXL-ALA 14.1 au, P < 0.001), whereas ALA over time overcame MAL and induced the highest fluorescence intensities obtained (t = 180 minutes, AFXL-MAL 98.6 vs. AFXL-ALA 112.0 au, P < 0.001). In deep skin layers, fluorescence microscopy showed higher fluorescence in hair follicle epithelium for ALA than MAL (t = 180 minutes, 1.8 mm, AFXL-MAL 35.3 vs. AFXL-ALA 46.7 au, P < 0.05). CONCLUSIONS: AFXL changes kinetics and biodistribution of ALA and MAL. It appears that AFXL-ALA favors targeting deep structures.

Three-dimensional volumetric quantification of fat loss following cryolipolysis.

BACKGROUND AND OBJECTIVES: Cryolipolysis is a noninvasive and well-tolerated treatment for reduction of localized subcutaneous fat. Although several studies demonstrate the safety and efficacy of this procedure, volumetric fat reduction from this treatment has not been quantified. This prospective study investigated the change in volume of fat after cryolipolysis treatment using three-dimensional (3D) photography. MATERIALS AND METHODS: A prospective study of subjects treated with cryolipolysis on the flank (love handle) was performed at Massachusetts General Hospital. Volume measurements were performed with a Canfield Scientific Vectra three-dimensional camera and software to evaluate the amount of post procedure volume change. Clinical outcomes were assessed with caliper measurements, subject surveys, and blinded physician assessment of photographs. RESULTS: Eleven subjects were enrolled in this study. Each subject underwent a single cycle of cryolipolysis to one flank. The untreated flank served as an internal control. The follow-up time after treatment was 2 months. The mean amount of calculated absolute fat volume loss using 3D photography from baseline to 2 months follow-up visit was 56.2 ± 25.6 from the treatment site and 16.6 ± 17.6 cc from the control (P < 0.0001). A mean absolute difference of 39.6 cc between the treated and untreated sides was calculated at 2 months post-treatment. Comparison of caliper measurements from baseline to 2 months post-treatment demonstrated significant reduction of the treated flank from 45.6 ± 5.8 mm at baseline to 38.6 ± 4.6 mm at 2 months post-treatment (P < 0.001). The untreated flank did not show significant reduction with caliper measurements demonstrating 45.3 ± 5.0 mm at baseline and 44.6 ± 5.1 mm at 2 months post-treatment (P = 0.360). No unexpected side effects or adverse events were reported. Post-treatment satisfaction surveys demonstrated 82% of subjects were satisfied with the results. CONCLUSIONS: Cryolipolysis is a safe, well-tolerated, and effective noninvasive fat removal methodology that on average leads to 39.6 cc of fat loss of the treated flank at 2 months after a single treatment cycle.

Fractional Skin Harvesting: Autologous Skin Grafting without Donor-site Morbidity.

BACKGROUND: Conventional autologous skin grafts are associated with significant donor-site morbidity. This study was conducted to determine feasibility, safety, and efficacy of a new strategy for skin grafting based on harvesting small columns of full-thickness skin with minimal donor-site morbidity. METHODS: The swine model was used for this study. Hundreds of full-thickness columns of skin tissue (~700 µm diameter) were harvested using a custom-made harvesting device, and then applied directly to excisional skin wounds. Healing in donor and graft sites was evaluated over 3 months by digital photographic measurement of wound size and blinded, computer-aided evaluation of histological features and compared with control wounds that healed by secondary intention or with conventional split-thickness skin grafts (STSG). RESULTS: After harvesting hundreds of skin columns, the donor sites healed rapidly without scarring. These sites reepithelialized within days and were grossly and histologically indistinguishable from normal skin within 7 weeks. By contrast, STSG donor sites required 2 weeks for reepithelialization and retained scar-like characteristics in epidermal and dermal architecture throughout the experiment. Wounds grafted with skin columns resulted in accelerated reepithelialization compared with ungrafted wounds while avoiding the "fish-net" patterning caused by STSG. CONCLUSION: Full-thickness columns of skin can be harvested in large quantities with negligible long-term donor-site morbidity, and these columns can be applied directly to skin wounds to enhance wound healing.