Melasma treatment with a 1064 nm, picosecond-domain laser with a fractionated multibeam lens array.

BACKGROUND AND OBJECTIVES: Picosecond-domain lasers have been fitted with fractionated optics for dermal remodeling. This study evaluates the safety and efficacy of a multiwavelength picosecond-domain laser, using a 1064 nm multibeam lens array, for improving the appearance of melasma. STUDY DESIGN/MATERIALS AND METHODS: Twenty adults with a clinical diagnosis of melasma were enrolled and received 4 monthly 1064-nm, 450 ps laser treatments delivered with a 10 × 10 fractional array of 150 µm microbeams. Cosmetic units with melasma were treated with fluences ranging from 1.7 to 2.9 mJ/microbeam with a repetition rate of 6 Hz. Treatment effect was evaluation of digital images by dermatologists blinded as to the treatment conditions, comparing baseline and 3- and 8-month post-treatment images. Modified melasma area and severity index (mMASI) scores were determined by the study investigator based on clinical photography. Subject self-assessment of treatment effects was also recorded. RESULTS: Blinded reviewers correctly identified the post-treatment image in 16 of the 20 image sets (80%). Ratings demonstrated statistically significant (p < 0.001) improvement on an 11-point scale at both the 3- and 8-month timepoints for a mean improvement of 3.7 point (range -8 to 10) or 37% improvement at the 3-month follow-up, and 2.7 (range -8 to 9) or 27% at the 8-month follow-up for all subjects. The average mMASI score showed highly significant reduction at both the 3- and 8-month follow-ups compared to baseline (p < 0.01). Most subjects (90%) were satisfied with the treatment outcome in melasma at both follow-ups, which is consistent with the treatment outcome and mMASI scores. CONCLUSION: The fractionated, picosecond-domain, 1064 nm laser is safe and effective for improving melasma and should be considered as an adjunct to topical treatment regimens and sun-protection for management of melasma.

A new 532 nm, variable-pulse-structure, dual-wavelength, KTP laser incorporating cryogen spray cooling, effectively treats rosacea.

BACKGROUND: A new dual-wavelength, high-energy, solid-state laser incorporating both 532 and 1064 nm wavelengths was developed with cryogen spray cooling and the unique ability to deliver three types of pulse structures including single pulses of a specific pulse-duration or pulses composed of a train of subpulses in the millisecond or microsecond domain with an intervening delay over the selected pulse-duration. We investigate the efficacy of this laser using all three pulse structures and the 532 nm wavelength for treating rosacea. METHODS: Twenty-one subjects were enrolled in this IRB-approved study. A total of up to three treatments were administered at monthly intervals. Each treatment consisted of a first pass tracing linear vessels with a 40 ms pulse-duration immediately followed by a second pass using a 5 ms pulse, using all three available pulse structures. Assessment of cross-polarized digital images by blinded physician observers compared baseline and 3-month follow-up images. RESULTS: Blinded observers correctly identified the posttreatment images 89% of the time, in 17 of 19 subjects completing the study, with an average overall improvement rating of 39% after only three treatments. Side effects were limited to short-term erythema and edema. CONCLUSION: This study demonstrates that this new, variable-pulse-structure, dual wavelength, solid state, KTP laser with dynamic cooling is a safe and effective for treating rosacea.

Low-fluence treatment with a novel fractionated 2,910-nm fiber laser improves photodamage.

BACKGROUND: Facial rejuvenation by lasers that target water has been a mainstay of esthetic laser treatments for decades. Modern lasers more commonly treat a fraction of the skin surface using ablative, semi-ablative, or nonablative pulses. METHODS: Twenty subjects with visible evidence of chronic photoaging on the face were enrolled in this study. All subjects received two full-face, single-pass treatments spaced 2 months apart with the superficial mode of a 2910 nm fiber laser with an estimated penetration depth of 10 µm, 25% coverage, delivered in a 15 mm × 15 mm square microbeam pattern. A blinded comparison of pretreatment and 3-month post-treatment images was performed. Evaluation of biopsy samples for laser-tissue effects was performed on three separate subjects and biopsies were harvested 1-day post-treatment, 1-week post-treatment, and 2-weeks post-treatment. RESULTS: Blinded evaluation of digital images revealed an average improvement score of 25.1 ± 14.5 (mean ± SEM) or 25.1%, using an 11-point scale evaluating overall improvement in photoaging (p < 0.001). Post-treatment effects were limited to mild-to-moderate erythema and edema, and the pain was rated a 1.9 out of a maximum of 10. Histology demonstrated superficial changes in the stratum corneum and epidermis with dermal inflammation present at 1-day post-treatment and 1-week post-treatment, with a return to baseline at 2 weeks. CONCLUSIONS: The 2910 nm fiber laser is safe and effective for improving mild photodamage, with minimal discomfort and downtime. Dermal inflammation results from very superficial epidermal injury and may contribute to clinical improvement.

Lack of attention to sex and gender in periodontitis-related randomized clinical trials: A meta-research study.

AIM: This meta-research study aimed to investigate the level of compliance with the Sex and Gender Equity in Research (SAGER) Guidelines for the inclusion, analysis, and reporting of sex/gender, in periodontitis-related randomized controlled trials (RCTs). MATERIALS AND METHODS: Following the inclusion of RCTs related to the treatment of periodontitis published between 2018 and 2019, we applied the SAGER checklist to assess the adherence to sex/gender reporting guidelines. We used non-parametric descriptive statistics and correlation models to test the association of the dependent outcome with other variables. RESULTS: One hundred and one articles were included in the analysis. The female enrolment ranged between 30% and 94%. Twenty-six studies enrolled less than 50% of female participants. The overall SAGER score (OSS) of item fulfilment ranged between 0 and 7 items with an average of 1.9 items signifying poor guideline adherence to the SAGER guidelines. These findings were not associated with the corresponding author gender (p = .623), publication year (p = .947), and funding source (p = .133). However, a significant but negative correlation with journal impact factor (r = -0.253, p = .026) was observed. CONCLUSIONS: Sex and gender were frequently disregarded in clinical trial reporting. This oversight might limit the understanding of sex/gender differences in periodontitis-related clinical trials.

Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a single-arm, phase 2 trial.

BACKGROUND: TGF-ß is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-ß blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-ß type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer. METHODS: This was an investigator-initiated, single-arm, phase 2 study done in two medical centres in Portland (OR, USA). Eligible patients had previously untreated, locally advanced, rectal adenocarcinoma, stage IIA-IIIC or IV as per the American Joint Committee on Cancer; Eastern Cooperative Oncology Group status 0-2; and were aged 18 years or older. Participants completed two 14-day courses of oral galunisertib 150 mg twice daily, before and during fluorouracil-based chemoradiotherapy (intravenous fluorouracil 225 mg/m2 over 24 h daily 7 days per week during radiotherapy or oral capecitabine 825 mg/m2 twice per day 5 days per week during radiotherapy; radiotherapy consisted of 50·4-54·0 Gy in 28-30 fractions). 5-9 weeks later, patients underwent response assessment. Patients with a complete response could opt for non-operative management and proceed to modified FOLFOX6 (intravenous leucovorin 400 mg/m2 on day 1, intravenous fluorouracil 400 mg/m2 on day 1 then 2400 mg/m2 over 46 h, and intravenous oxaliplatin 85 mg/m2 on day 1 delivered every 2 weeks for eight cycles) or CAPEOX (intravenous oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks for four cycles). Patients with less than complete response underwent surgical resection. The primary endpoint was complete response rate, which was a composite of pathological complete response in patients who proceeded to surgery, or clinical complete response maintained at 1 year after last therapy in patients with non-operative management. Safety was a coprimary endpoint. Both endpoints were assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02688712, and is active but not recruiting. FINDINGS: Between Oct 19, 2016, and Aug 31, 2020, 38 participants were enrolled. 25 (71%) of the 35 patients who completed chemoradiotherapy proceeded to total mesorectal excision surgery, five (20%) of whom had pathological complete responses. Ten (29%) patients had non-operative management, three (30%) of whom ultimately chose to have total mesorectal excision. Two (67%) of those three patients had pathological complete responses. Of the remaining seven patients in the non-operative management group, five (71%) had clinical complete responses at 1 year after their last modified FOLFOX6 infusion. In total, 12 (32% [one-sided 95% CI ≥19%]) of 38 patients had a complete response. Common grade 3 adverse events during treatment included diarrhoea in six (16%) of 38 patients, and haematological toxicity in seven (18%) patients. Two (5%) patients had grade 4 adverse events, one related to chemoradiotherapy-induced diarrhoea and dehydration, and the other an intraoperative ischaemic event. No treatment-related deaths occurred. INTERPRETATION: The addition of galunisertib to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer improved the complete response rate to 32%, was well tolerated, and warrants further assessment in randomised trials. FUNDING: Eli Lilly via ExIST program, The Providence Foundation.

Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

A laser platform incorporating a novel 524 nm laser pumped by a commercial hair removal laser effectively treats facial redness and lower-extremity spider veins.

BACKGROUND AND OBJECTIVES: Treatment of vascular lesions is one of the main applications of cutaneous laser technology, while the other is laser hair removal. We present here a vascular laser pumped by a commercial hair removal laser. STUDY DESIGN/MATERIALS AND METHODS: A novel 524 nm vascular laser was designed using a 755 nm hair removal laser as a pumping source. This 524 nm vascular laser was used to treat facial redness and leg telangiectasias in 24 subjects. Four treatments were administered to the face at 4-6-week intervals and final photographs were taken 8 weeks following the final treatment, while two treatments were administered to lower-extremity spider veins at 2-month intervals with follow-up photographs 3 months following the final treatment. Blinded analysis of digital images was performed by two physicians not involved in the study. RESULTS: Blinded evaluation of digital photographs revealed an average improvement score of 3.3 ± 1.7 (mean ± SEM) on a 0-10 scale for removing facial redness (p < 0.001), representing a 33% improvement. Leg veins improved an average of 51% corresponding to a score of 5.1 ± 2.0 (p < 0.001). Side effects were mild and limited to erythema, purpura, edema, and one instance of mild hyperpigmentation. CONCLUSIONS: This novel 524 nm laser is safe and effective for treating vascularity on the face and legs, and proves the ability to create a laser platform incorporating a hair removal laser which then can be used as a pumping source for the attached vascular laser module.

Clinical Relevance of Elastin in the Structure and Function of Skin.

Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin's structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin's appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

The First Commercial 730 nm Picosecond-Domain Laser is Safe and Effective for Treating Multicolor Tattoos.

BACKGROUND AND OBJECTIVES: Laser-pumped lasers enable driving a secondary wavelength through pumping with a primary device. Here we investigate the first 730 nm laser-pumped laser for efficacy in tattoo removal. STUDY DESIGN/MATERIALS AND METHODS: Fifteen subjects with 20 tattoos were enrolled to investigate the effect of a new 730 nm, titanium-sapphire laser-pumped laser at removing decorative tattoos. A total of four treatments were administered and photographic improvement of pre- and post-treatment cross-polarized digital images was evaluated by four blinded physician observers using an 11-point scale. RESULTS: Blinded assessment of pre- and post-treatment images found 70%, 77%, 83%, 83%, 26%, and 8% clearance from baseline images for black, green, blue, purple, red and yellow pigments, respectively. Side effects were limited to pinpoint bleeding and erythema immediately after treatment and some crusting and scale up to 1-2 weeks following treatment, and a localized allergic reaction in a single subject. There was no scarring or pigmentary alteration visible in any follow-up images. CONCLUSION: The new 730 nm, picosecond-domain, titanium-sapphire, laser-pumped laser is safe and effective for removing multicolored tattoos. Green, blue, and purple pigments cleared the most as expected, but black ink cleared more completely than was predicted. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Iron oxides in novel skin care formulations attenuate blue light for enhanced protection against skin damage.

BACKGROUND: Ultraviolet (UV) radiation is a main cause of aging of sun-exposed skin, but greater attention is being focused on the damaging effects of high-energy visible (HEV) light (400 and 500 nm). HEV light exposure has increased with expanding use of consumer electronics, such as smartphones, which have a peak emission in the 400-490 nm range. Sunscreens containing titanium dioxide and zinc oxide protect against UVA and UVB radiation but provide limited protection against HEV light. AIM: Iron oxides including red iron oxide (Fe2 O3 ), yellow iron oxide (Fe(OH)3 /FeOOH), and black iron oxide (Fe3 O4 ) effectively block HEV light, each with a different attenuation profile. Zinc oxide, titanium dioxide, and iron oxides with patented skin care ingredients have been incorporated into several formulations to provide enhanced skin protection (Colorescience, Inc). METHODS: The percent of HEV light attenuation from 400 nm to 490 nm light was measured in vitro using a technique known as diffuse transmittance spectroscopy using a Perkin Elmer Lambda™ 750 UV/Vis/NIR Spectrophotometer equipped with a 100-mm integrating Labsphere® and PbS detector. RESULTS: Products formulated with zinc oxide, titanium dioxide, and iron oxides demonstrated 71.9%-85.6% attenuation across the tested wavelengths of 415-465 nm. CONCLUSION: Sunscreens formulated with iron oxides provide enhanced protection against blue light, especially when combined with zinc oxide. To our knowledge, similar studies with iron oxides have not been performed.

Oral isotretinoin and photoaging: A review.

INTRODUCTION: Over the past 20 years, evidence has emerged indicating oral isotretinoin could be considered a potential treatment for photoaged skin. In this review, we provide a succinct overview of the available evidence and provide commentary on the current and future directions for utilizing oral isotretinoin as a potential treatment for photoaging. METHODS: We prepared a review protocol and searched the PubMed and Cochrane databases for relevant literature published between January 1982 and April 2020. Using a defined keyword search, a total of 23 papers were initially identified by the main author. Two authors independently reviewed each of the 23 articles, and 6 articles were deemed relevant to this study. RESULTS: Of the six studies included in this review, three were randomized clinical trials, one was a nonrandomized clinical trial and two were prospective cohort studies. All studies were conducted between 2000 and 2015. Across all 6 studies, 251 patients were recruited, with a mean of 42 patients per study. Four studies were in favor of isotretinoin to improve photoaged skin, 1 study showed no benefit, and 1 study showed no benefit when compared to topical tretinoin treatment. Of the studies available, many were hampered by methodological challenges. CONCLUSION: Oral isotretinoin may be useful for treating photoaging but there is currently insufficient evidence to support its use. In comparison with other established anti-photoaging treatments, it is not clear whether the potential benefits of oral isotretinoin outweigh the potential risks.

Beyond sun protection factor: An approach to environmental protection with novel mineral coatings in a vehicle containing a blend of skincare ingredients.

BACKGROUND: Premature skin aging results from exposure to a range of environmental factors, primarily ultraviolet radiation, but also high-energy visible light in the blue spectrum, infrared radiation, and environmental pollution. These extrinsic factors result in the generation of reactive oxygen species which promote photoaging and DNA damage resulting in skin cancers. AIMS: To formulate skincare products utilizing a new coating applied to zinc oxide and titanium dioxide particles and complimentary skincare ingredients to provide broad protection against a range of environmental insults. METHODS: A cross-polymer, multifunctional coating of silicate, polyalkylsilsesquioxane, and polydimethylsiloxane moieties increases the photostability and decreases the reactivity of mineral sunscreen agents when interacting with energy sources. These products are also formulated with antioxidants to minimize free radical propagation. Additionally, this coating improves the esthetic feel of mineral sunscreens, while the appearance is enhanced by formulating products with a blend of iron oxides. RESULTS: A series of in vitro and ex vivo studies demonstrated the ability of mineral-based products formulated with the new multifunctional coating to provide protection against ultraviolet radiation, high-energy visible light, infrared radiation, and environmental pollution. CONCLUSION: Newly formulated mineral-based skincare products provide environmental protection, are ecologically safe, and can replace chemical-based sunscreen ingredients.

Cytotoxicity of aqueous cigarette smoke extract is affected by properties of pipettes used to prepare the extract.

Cigarette smoke contains a host of molecules including toxins and carcinogens, most of which have not been well studied. Aqueous cigarette smoke extract (CSE) is one of various cigarette smoke derivatives that can be used for in vitro studies, and the influence of different method parameters on CSE composition and toxicity remains incompletely understood. Herein, we prepared CSE by bubbling cigarette smoke through mammalian cell culture medium, varying the type of pipette inserted into the recipient medium. Changing this one component of the preparation apparatus had a marked effect on the toxicity of the resulting CSE. Since many other parameters can also be varied in CSE preparation, these results stress the importance of standardization within and between studies.

Treatment of poikiloderma of Civatte using a redesigned pulsed dye laser with a 15 mm diameter treatment spot.

OBJECTIVES: The pulsed-dye laser has long been a gold standard in the treatment of poikiloderma of Civatte. Recent advances in pulsed dye laser technology enable output energies 50% higher, enabling beam diameters of up to 15 mm with clinically relevant fluences. In this study, we investigate this new laser for treatment of this condition. MATERIALS AND METHODS: Twenty subjects were enrolled in the study. A total of four treatments were administered at monthly intervals. Blinded assessment of digital, cross-polarized photographs taken at baseline and two months following the last treatment was performed by blinded physician raters using an 11-point clearance scale. Subject reported pain scores immediately following treatment and side effects at all visits were recorded by the investigator. RESULTS: Seventeen subjects completed the study. Blinded reviewers correctly identified the baseline photo in 48 of 51 cases (94%). All three reviewers mis-identified the same subjects. The blinded reviewers scored 14 out of the 17 subjects with an improvement greater than 40% and 10 out of the 17 subjects greater than 50%. Average improvement was 49% for all 17 subjects. Side effects were limited to mild edema, and mild to moderate erythema and purpura. Pain scores averaged 3.5 on using an 11-point scale. CONCLUSION: This study demonstrates the safety and effectiveness of a new pulsed-dye laser with a 15 mm spot and 50% higher fluences for the treatment of poikiloderma of Civatte. Lasers Surg. Med. 51:54-58, 2019. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

A novel titanium sapphire picosecond-domain laser safely and effectively removes purple, blue, and green tattoo inks.

BACKGROUND: Green, blue, and purple tattoo pigments are often the colors most resistant to laser removal. Recently, the first ever production picosecond-domain laser with a 785 nm wavelength was developed to improve the rate of clearance of green, blue, and purple tattoo inks. METHODS: Twenty-two tattoos from 15 subjects with skin phototypes II-IV were enrolled in the study. A total of four treatments were administered using a single 785 nm picosecond-domain laser wavelength. Blinded assessment of digital, cross-polarized photographs taken approximately 8 weeks following the last treatment was performed using an 11-point clearance scale. RESULTS: Fourteen subjects with 21 tattoos completed all study visits. The 21 tattoos contained the following pigments: black (n = 15), green (n = 13), blue (n = 8), yellow (n = 5), purple (n = 4), and red (n = 3). Treatments were performed with a 2-4-mm beam diameter and fluences ranging from 1.1 to 3.1 J/cm2 . Blinded assessment of photographs found 85%, 81%, 74%, 61%, 11%, and 5% clearance from baseline photos for purple, blue, green, black, red, and yellow pigments, respectively. Treatments were well tolerated with typical erythema, edema and one case of pinpoint bleeding. No scarring was noted. CONCLUSION: This first study of a new 785 nm picosecond-domain laser demonstrates safe and effective removal of multicolor tattoos. Although clearance was shown for a multitude of colors including black, the 785 nm laser wavelength has special affinity to purple, blue and green tattoo pigments. Lasers Surg. Med. 9999:1-7, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.