Limited health insurance coverage of injectable neurotoxins and fillers for gender affirmation: a cross-sectional study of Affordable Care Act silver and Medicaid plans.

Background: Injectable neurotoxins and fillers are potential options for facial gender affirmation for transgender/nonbinary patients. However, the largest barrier to access is cost/insurance coverage. Objective: The purpose of this article is to assess the extent to which Affordable Care Act (ACA) silver plans and Medicaid policies cover gender-affirming injectable neurotoxin and filler procedures. Methods: A cross-sectional study of all ACA silver plans and Medicaid policies was performed from June 22 to August 15, 2021. Plan-specific certificates of coverage, clinical policies of insurance providers, and Medicaid documents were evaluated. Results: A total of 915 plans were reviewed (864 ACA silver plans and all 51 Medicaid policies). None potentially covered neurotoxins. Only 72 (71 ACA and 1 Medicaid) potentially covered fillers, specifically collagen injections and lipofilling. Coverage required demonstration of medical necessity or significant variation of physical appearance from the patient's experienced gender. However, of the 71 ACA plans, 69 outlined cosmetic exclusions, possibly nullifying this coverage. Limitations: Data were sourced from publicly available online information in 2021. Additionally, we were unable to confirm explicit coverage of these procedures with insurance companies. Conclusion: The majority of ACA silver and Medicaid plans did not cover gender-affirming neurotoxin or filler procedures, limiting access to this gender-affirming care.

Implications for cumulative and prolonged clinical improvement induced by cross-linked hyaluronic acid: An in vivo biochemical/microscopic study in humans.

In photoaged human skin, type I collagen fragmentation impairs dermal extracellular matrix (ECM) integrity, resulting in collapsed/contracted fibroblasts with reduced type I procollagen synthesis. Injections of cross-linked hyaluronic acid (CL-HA) reverse these deleterious changes. To investigate the time course and effects of biochemical changes induced by injected CL-HA, particularly whether fibroblast activation leads to accumulation/deposition of dermal collagen, we injected CL-HA into photoaged skin of human participants over 60 years-old and performed biochemical/microscopic analyses of skin samples. Beginning 1 week post-injection and lasting 6-9 months, fibroblasts exhibited activation, including increased immunostaining and gene expression of markers of type I collagen synthesis, such as heat shock protein 47 and components of the transforming growth factor-ß pathway. At 1 week post-injection, multiphoton microscopy revealed elongation/stretching of fibroblasts, indicating enhanced dermal mechanical support. At 4 weeks, second-harmonic generation microscopy revealed thick collagen bundles densely packed around pools of injected CL-HA. At 12 months, accumulation of thick collagen bundles was observed and injected CL-HA remained present in substantial amounts. Thus, by occupying space in the dermal ECM, injected CL-HA rapidly and durably enhances mechanical support, stimulating fibroblast elongation and activation, which results in thick, densely packed type I collagen bundles accumulating as early as 4 weeks post-injection and continuing for at least a year. These observations indicate that early and prolonged clinical improvement following CL-HA injection results from space-filling and collagen deposition. As type I collagen has an estimated half-life of 15 years, our data provide the foundations for optimizing the timing/frequency of repeat CL-HA injections.

Cutaneous Hypervascularization Treatment Using Photo-Mediated Ultrasound Therapy.

Photo-mediated ultrasound therapy (PUT) is a cavitation-based, highly selective antivascular technique. In this study, the effectiveness and safety of PUT on cutaneous vascular malformation was examined through in vivo experiments in a clinically relevant chicken wattle model, whose microanatomy is similar to that of port-wine stain and other hypervascular dermal diseases in humans. Assessed by optical coherence tomography angiography, the blood vessel density in the chicken wattle decreased by 73.23% after one session of PUT treatment in which 0.707 J/cm2 fluence laser pulses were applied concurrently with ultrasound bursts (n = 7, P < .01). The effectiveness of removing blood vessels in the skin at depth up to 1 mm was further assessed by H&E-stained histology at multiple time points, which included days 1, 3, 7, 14, and 21 after treatment. Additional immunohistochemical analyses with CD31, caspase-3, and Masson's trichrome stains were performed on day 3 after treatment. The results show that the PUT-induced therapeutic effect was confined and specific to blood vessels only, whereas unwanted collateral damage in other skin tissues such as collagen was avoided. The findings from this study demonstrate that PUT can efficiently and safely remove hypervascular dermal capillaries using laser fluence at a level that is orders of magnitude smaller than that used in conventional laser treatment of vascular lesions, thus offering a safer alternative technique for clinical management of cutaneous vascular malformations.

Needs and Gaps in Resident Trainee Education, Clinical Patient Care, and Clinical Research in Cosmetic Dermatology: Position Statement of the Association of Academic Cosmetic Dermatology.

Cosmetic dermatology is a key subspecialty of academic dermatology. As such, academic centers are expected to demonstrate excellence in the teaching of cosmetic dermatology skills to trainees, the clinical delivery of cosmetic dermatology services to patients, and the performance of clinical research that advances knowledge and uncovers new therapies in cosmetic dermatology. The Association of Academic Cosmetic Dermatology (AACD), a newly formed medical professional society, includes as its principal aims the support of all of these areas. AACD is comprised of group of board-certified dermatologists who teach cosmetic and laser dermatology at US dermatology residency programs. An expert panel constituted by the AACD recently convened a workshop to review gaps pertaining to academic cosmetic dermatology. This panel considered needs and potential corrective initiatives in three domains: resident education, patient experience, and clinical research. The work of the panel was used to develop a roadmap, which was adopted by consensus, and which will serve to guide the AACD moving forward.

The Association of Academic Cosmetic Dermatology: improving cosmetic dermatology education through collaboration, research, and advocacy.

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.

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.

Removing Subcutaneous Microvessels Using Photo-Mediated Ultrasound Therapy.

BACKGROUND AND OBJECTIVES: We have developed a novel anti-vascular technique, termed photo-mediated ultrasound therapy (PUT), which utilizes nanosecond duration laser pulses synchronized with ultrasound bursts to remove the microvasculature through cavitation. The objective of the current study is to explore the potential of PUT in removing subcutaneous microvessels. STUDY DESIGN/MATERIALS AND METHODS: The auricular blood vessels of two New Zealand white rabbits were treated by PUT with a peak negative ultrasound pressure of 0.45 MPa at 0.5 MHz, and a laser fluence of 0.056 J/cm2 at 1064 nm for 10 minutes. Blood perfusion in the treated area was measured by a commercial laser speckle imaging (LSI) system before and immediately after treatment, as well as at 1 hour, 3 days, 2 weeks, and 4 weeks post-treatment. Perfusion rates of 38 individual vessels from four rabbit ears were tracked during this time period for longitudinal assessment. RESULTS: The measured perfusion rates of the vessels in the treated areas, as quantified by the relative change in perfusion rate, showed a statistically significant decrease for all time points post-treatment (P < 0.001). The mean decrease in perfusion is 50.79% immediately after treatment and is 32.14% at 4 weeks post-treatment. Immediately after treatment, the perfusion rate decreased rapidly. Following this, there was a partial recovery in perfusion rate up to 3 days post-treatment, followed by a plateau in the perfusion from 3 days to 4 weeks. CONCLUSIONS: This study demonstrated that a single PUT treatment could significantly reduce blood perfusion by 32.14% in the skin for up to 4 weeks. With unique advantages such as low laser fluence as compared with photothermolysis and agent-free treatment as compared with photodynamic therapy, PUT holds the potential to be developed into a new tool for the treatment of cutaneous vascular lesions. Lasers Surg. Med. © 2020 Wiley Periodicals, LLC.

CD26 Identifies a Subpopulation of Fibroblasts that Produce the Majority of Collagen during Wound Healing in Human Skin.

Fibroblasts produce collagens and other proteins that form the bulk of the extracellular matrix (ECM) in connective tissues. Emerging data point to functional heterogeneity of fibroblasts. However, the lack of subtype-specific markers hinders our understanding of the different roles of fibroblasts in ECM biology, wound healing, diseases, and aging. We have investigated the utility of the cell surface protein CD26 to identify functionally distinct fibroblast subpopulations in human skin. Using flow cytometry and immunohistology, we found that CD26, in combination with the cell surface glycoprotein CD90, identifies a distinct subpopulation of cells, which express relatively high levels of COL1A1, a hallmark of fibroblasts. Importantly, the population of CD26+ fibroblasts is selectively increased after wounding of human skin. These cells account for the majority of COL1A1 expression during the ECM remodeling phase of healing. The proportion of CD26+ fibroblasts in the skin of young and aged individuals is similar, indicating that the loss of collagen production during aging does not involve selective reduction of CD26+ fibroblasts. In culture, the majority of freshly isolated CD26- fibroblasts gain expression of CD26+. Taken together, these data provide a foundation for targeting CD26+ fibroblasts to modulate wound healing in human skin.

Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin.

Human skin heals more slowly in aged vs. young adults, but the mechanism for this delay is unclear. In humans, eccrine sweat glands (ESGs) and hair follicles underlying wounds generate cohesive keratinocyte outgrowths that expand to form the new epidermis. Here, we compared the re-epithelialization of partial-thickness wounds created on the forearm of healthy young (< 40 yo) and aged (> 70 yo) adults. Our results confirm that the outgrowth of cells from ESGs is a major feature of repair in young skin. Strikingly, in aged skin, although ESG density is unaltered, less than 50% of the ESGs generate epithelial outgrowths during repair (vs. 100% in young). Surprisingly, aging does not alter the wound-induced proliferation response in hair follicles or ESGs. Instead, there is an overall reduced cohesiveness of keratinocytes in aged skin. Reduced cell-cell cohesiveness was most obvious in ESG-derived outgrowths that, when present, were surrounded by unconnected cells in the scab overlaying aged wounds. Reduced cell-cell contact persisted during the repair process, with increased intercellular spacing and reduced number of desmosomes. Together, reduced outgrowths of ESG (i) reduce the initial number of cells participating in epidermal repair, (ii) delay wound closure, and (iii) lead to a thinner repaired epidermis in aged vs. young skin. Failure to form cohesive ESG outgrowths may reflect impaired interactions of keratinocytes with the damaged ECM in aged skin. Our findings provide a framework to better understand the mediators of delayed re-epithelialization in aging and further support the importance of ESGs for the repair of human wounds.

A gender-based comparison of pain tolerance during pulsed dye laser therapy.

BACKGROUND: Cosmetic laser treatments are frequently performed without anesthesia in the clinic setting and there is a need to better understand the factors that may impact patient pain levels during these procedures. There has been prior research suggesting that there are significant gender-based differences in pain experiences with a variety of interventions. AIMS: We sought to examine the influence of gender and specific emotional factors on pain perception during pulsed dye laser treatments. PATIENTS/METHODS: We conducted a questionnaire-based study of 84 adult patients (42 males and 42 females) who underwent facial pulsed dye laser treatments in our clinic for cosmetic purposes. Questionnaires were completed by each patient after his or her initial laser treatment and patients were queried as to their perceived levels of pain during the procedure. Additional information regarding quality of life measures and patient motivation was also collected. RESULTS: Contrary to prior research suggesting lower pain thresholds for women in other clinical or experimental settings, we found no statistically significant differences in mean pain levels reported between patients of each gender. There was a trend toward females being somewhat more likely than males to see the pain of the treatment as justified for an improvement in appearance. CONCLUSIONS: Patient motivation and pain tolerance levels may be similar between genders among patients undergoing non-invasive cosmetic procedures. Clinicians may, therefore, expect patients of either gender to tolerate such treatments equally well.

A multistep approach to improving biopsy site identification in dermatology: physician, staff, and patient roles based on a Delphi consensus.

IMPORTANCE: Excisional skin cancer surgery is a common procedure, with no formal consensus for mitigating the risk of wrong-site cutaneous surgery. OBJECTIVE: To systematically consider the usefulness and feasibility of proposed methods for correct biopsy site identification in dermatology. EVIDENCE REVIEW: Survey study with a formal consensus process. Item development was via a literature review and expert interviews, followed by 2 stages of a Delphi process to develop consensus recommendations. FINDINGS: In total, 2323 articles were reviewed in the literature search, with data extraction from 14. Twenty-five experts underwent 30-minute structured interviews, which were transcribed and coded. The resulting survey was composed of 42 proposed interventions by multiple stakeholders (biopsying physicians, operating physicians, nurses, ancillary staff, patients, caregivers, and family members) at 3 time points (day of biopsy, delay and consultation period, and day of definitive surgery). Two rounds of a Delphi process with 59 experts (25 academic and 34 private practice) scored the survey. Strong consensus was obtained on 14 behaviors, and moderate consensus was obtained on 21 other behaviors. In addition, a 2-state simultaneous algorithm was developed to model surgeon behavior on the day of definitive surgery based on surgeon and patient perceptions. CONCLUSIONS AND RELEVANCE: When definitive surgery is performed after the initial biopsy and by a different surgeon, procedures can be implemented at several time points to increase the likelihood of correct site identification. The specific circumstances of a case suggest which methods may be most appropriate and feasible, and some may be implemented. The risk of wrong-site cutaneous surgery can be reduced but not eliminated.

Hypo-collagenesis in photoaged skin predicts response to anti-aging cosmeceuticals.

BACKGROUND: Chronic sun exposure causes photoaging, the appearance of prematurely aged skin. This phenomenon is characterized by progressive alteration of the dermal extracellular matrix, including elastin and collagen fibers. While many cosmeceuticals claim to improve the appearance of photoaged skin, data are lacking regarding their ability to induce molecular responses associated with wrinkle effacement, particularly increased collagen production. AIMS: To conduct a meta-analysis to determine whether there was a factor(s) that could predict response to various cosmeceuticals. PATIENTS/METHODS: Hundred subjects enrolled in five separate studies of cosmeceuticals containing: L-ascorbic acid, pentapeptide, α-lipoic acid, yeast extract, or 1% idebenone. Five groups consisting of 16-20 volunteers applied one cosmeceutical to their photodamaged forearms for several weeks. Punch biopsies were obtained pretreatment and post-treatment and analyzed for type I procollagen by ELISA. RESULTS: Analysis of basal collagenesis reinforced the notion that hypo-collagenesis is associated with photoaging severity, independent of age or gender. Treatment outcome varied greatly among subjects, ranging from no improvement to a 7-fold increase in collagenesis. Retrospective statistical meta-analysis was conducted to determine whether age, gender, type of cosmeceutical, or evidence of hypo-collagenesis in untreated skin could predict responsiveness to cosmeceuticals. Our analysis revealed that subjects with hypo-collagenesis responded 6.4 times more often than subjects with normo-collagenesis. DISCUSSION: Hypo-collagenesis was the only factor that influenced treatment outcome. This study therefore identifies hypo-collagenesis as the unique parameter predicting anti-aging cosmeceutical treatment outcome. These findings provide a basis for future cosmetic testing and the potential development of custom formula skin care.

Abbreviations for device names: a proposed methodology with specific examples.

BACKGROUND: Many devices used in dermatology lack generic names. If investigators use commercial device names, they risk the appearance of bias. Alternatively, reliance on ad-hoc names and abbreviations may confuse readers who do not recognize these. OBJECTIVE: To develop a system for assigning abbreviations to denote devices commonly used in dermatology. Secondarily, to use this system to create abbreviations for FDA-approved neurotoxins and prepackaged injectable soft-tissue augmentation materials. METHODS: The American Society for Dermatologic Surgery convened a Lexicon Task Force in March 2012. One charge of this Task Force was to develop criteria for assigning abbreviations to medical devices. A modified consensus process was used. RESULTS: Abbreviations to denote devices were to be: based on a standardized approach; transparent to the casual reader; markedly brief; and in all cases, different than the commercial names. Three-letter all caps abbreviations, some with subscripts, were assigned to denote each of the approved neurotoxins and fillers. CONCLUSION: A common system of abbreviations for medical devices in dermatology may avoid the appearance of bias while ensuring effective communication. The proposed system may be expanded to name other devices, and the ensuing abbreviations may be suitable for journal articles, continuing medical education lectures, or other academic or clinical purposes.

Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo.

The dermal extracellular matrix (ECM) provides strength and resiliency to skin. The ECM consists mostly of type I collagen fibrils, which are produced by fibroblasts. Binding of fibroblasts to collagen fibrils generates mechanical forces, which regulate cellular morphology and function. With aging, collagen fragmentation reduces fibroblast-ECM binding and mechanical forces, resulting in fibroblast shrinkage and reduced function, including collagen production. Here, we report that these age-related alterations are largely reversed by enhancing the structural support of the ECM. Injection of dermal filler, cross-linked hyaluronic acid, into the skin of individuals over 70 years of age stimulates fibroblasts to produce type I collagen. This stimulation is associated with localized increase in mechanical forces, indicated by fibroblast elongation/spreading, and mediated by upregulation of type II TGF-ß receptor and connective tissue growth factor. Interestingly, enhanced mechanical support of the ECM also stimulates fibroblast proliferation, expands vasculature, and increases epidermal thickness. Consistent with our observations in human skin, injection of filler into dermal equivalent cultures causes elongation of fibroblasts, coupled with type I collagen synthesis, which is dependent on the TGF-ß signaling pathway. Thus, fibroblasts in aged human skin retain their capacity for functional activation, which is restored by enhancing structural support of the ECM.

Eccrine sweat glands are major contributors to reepithelialization of human wounds.

Eccrine sweat glands are skin-associated epithelial structures (appendages) that are unique to some primates including humans and are absent in the skin of most laboratory animals including rodents, rabbits, and pigs. On the basis of the known importance of other skin appendages (hair follicles, apocrine glands, and sebaceous glands) for wound repair in model animals, the present study was designed to assess the role of eccrine glands in the repair of wounded human skin. Partial-thickness wounds were generated on healthy human forearms, and epidermal repair was studied in skin biopsy samples obtained at precise times during the first week after wounding. Wound reepithelialization was assessed using immunohistochemistry and computer-assisted 3-dimensional reconstruction of in vivo wounded skin samples. Our data demonstrate a key role for eccrine sweat glands in reconstituting the epidermis after wounding in humans. More specifically, (i) eccrine sweat glands generate keratinocyte outgrowths that ultimately form new epidermis; (ii) eccrine sweat glands are the most abundant appendages in human skin, outnumbering hair follicles by a factor close to 3; and (iii) the rate of expansion of keratinocyte outgrowths from eccrine sweat glands parallels the rate of reepithelialization. This novel appreciation of the unique importance of eccrine sweat glands for epidermal repair may be exploited to improve our approaches to understanding and treating human wounds.

Direct quantitative comparison of molecular responses in photodamaged human skin to fractionated and fully ablative carbon dioxide laser resurfacing.

BACKGROUND: Fractionated ablative laser resurfacing has become a widely used treatment modality. Its clinical results are often found to approach those of traditional fully ablative laser resurfacing. OBJECTIVE: To directly compare the molecular changes that result from fractionated and fully ablative carbon dioxide (CO(2)) laser resurfacing in photodamaged human skin. METHODS AND MATERIALS: Photodamaged skin of 34 adult volunteers was focally treated at distinct sites with a fully ablative CO(2) laser and a fractionated CO(2) laser. Serial skin samples were obtained at baseline and several time points after treatment. Real-time reverse transcriptase polymerase chain reaction technology and immunohistochemistry were used to quantify molecular responses to each type of laser treatment. RESULTS: Fully ablative and fractionated CO(2) laser resurfacing induced significant dermal remodeling and collagen induction. After a single treatment, fractionated ablative laser resurfacing resulted in collagen induction that was approximately 40% to 50% as pronounced as that induced by fully ablative laser resurfacing. CONCLUSIONS: The fundamental cutaneous responses that result from fully ablative and fractionated carbon dioxide laser resurfacing are similar but differ in magnitude and duration, with the fully ablative procedure inducing relatively greater changes including more pronounced collagen induction. However, the molecular data reported here provide substantial support for fractionated ablative resurfacing as an effective treatment modality for improving skin texture.