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Caveolae are flask-shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components that allow compartmentalization and orchestration of various signalling molecules. In this review, we discuss how pleiotropic functions of caveolin-1 (Cav1) and its intricate roles in numerous cellular functions including lipid trafficking, signalling, cell migration and proliferation, as well as cellular senescence, infection and inflammation, are integral for normal development and functioning of skin and its appendages. We then examine how disruption of the homeostatic levels of Cav1 can lead to development of various cutaneous pathophysiologies including skin cancers, cutaneous fibroses, psoriasis, alopecia, age-related changes in skin and aberrant wound healing and propose how levels of Cav1 may have theragnostic value in skin physiology/pathophysiology., (© 2019 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Gemcitabine, a pyrimidine nucleoside analogue, is an oncologic agent used in the treatment of cutaneous T-cell lymphoma (CTCL). Common dermatologic reactions associated with gemcitabine include alopecia, mild skin rash, and mucositis but skin necrosis is exceptional. Herein we present an unusual case of widespread skin necrosis mimicking toxic epidermal necrolysis in a 45-year-old woman receiving gemcitabine therapy for stage IIIA cutaneous T-cell lymphoma. This is the first reported case of a TEN-like reaction subsequent to gemcitabine treatment. J Drugs Dermatol. 2018;17(5):582-585.

Understanding and managing patients' expectations can help improve their adherence to treatment for chronic wounds; however, little is known concerning about their expectations regarding healing time. Recruited subjects were asked to predict how long their wounds would take to heal and their charts were reviewed to retrieve real time of healing. We recruited 100 subjects from which 77% have healed. Fifty-three subjects (68.8%) had a longer healing time than they predicted (underestimated), and 17 (22.1%) had a shorter healing time than they predicted (overestimated). Subjects with shorter wound duration history tended to predict shorter healing time than subjects with longer wound duration (p < 0.01). However, wound duration did not affect prediction accuracy (p = 0.65). Subjects with chronic wounds seem more often to underestimate their time of healing. Wound duration significantly influenced patients' prediction time, although it did not make their prediction more accurate. Patient education about expectations may be important as patients often expect their wounds to heal faster than they actually do., (© 2018 by the Wound Healing Society.)

A variety of tumors may involve the eyelid, most of which are primary, but rarely can be metastatic. Previously reported eyelid primary carcinomas with neuroendocrine features include Merkel cell carcinoma, apocrine and eccrine gland carcinoma, sebaceous gland carcinoma, and one report of primary "well-differentiated neuroendocrine tumor." Herein we report the first case of primary cribriform carcinoma of the eyelid with neuroendocrine features. The patient is a 75-year-old black man who presented to the clinic with a 5-year history of a slowly growing, non-painful, non-exudative lesion of his left lower eyelid. Examination disclosed a non-tender 8 mm by 9 mm ovoid, firm, euchromic subdermal non-adherent nodule involving the left lower eyelid with no madarosis or loss of lid margin architecture, but with overlying induration. An incisional biopsy demonstrated nodules and aggregates of tumor composed of cuboidal hyperchromatic basoloid cells with occasional mitotic figures within sheets in a mostly cribriform and occasionally papillary pattern. The tumor was diffusely positive for cytokeratin, Epithelial Membrane Antigen, and p40 and focally positive for synaptophysin. The tumor was negative with antibodies for Cytokeratin 20 (CK20), p63, CD10, Thyroid Transcription Factor-1, Cytokeratin 7, Prostate Specific Antigen, and Epithelial Specific Antigen. Oncologic evaluation was negative for metastases. The patient underwent a complete excision of his eyelid tumor with 5 mm margins using Mohs surgery, with subsequent reconstruction using a Hughes tarsoconjunctival flap, myocutaneous advancement flap, and lateral canthal tendon plication.

J Drugs Dermatol. 2017;16(2):173-174.

Venous leg ulcers (VLUs) have higher tumor necrosis factor-α (TNF-α) levels compared with normal skin. Refractory VLUs of long duration have higher TNF-α levels compared with VLUs of shorter duration. As up to 75% of VLUs fail to heal with standard care, we sought to evaluate the role of anti-TNF-α therapy for patients with refractory VLUs. Evaluable data were obtained in four of five subjects with recalcitrant VLUs treated with 80 mg of subcutaneous adalimumab at week 0 and with 40 mg at week 2 along with compression therapy and were followed-up for 6 weeks. Wound biopsies taken at weeks 0 and 4 were stained with anti-TNF-α antibodies. Average 4-week percent wound size reduction was 20.5% ± 6.4%. Two patients had wound size reduction more than 25%, and their percent wound size reduction correlated to percent TNF-α staining score reductions (P = 0.02, R(2) = 0.999). VLU TNF-α level decrease 4 weeks post-adalimumab treatment correlated with wound healing., (© 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Wound healing is a dynamic process whereby cells, growth factors (GFs), and the extracellular matrix (ECM) interact to restore the architecture of damaged tissue. Chronic wounds can be difficult to treat due to the increased presence of inflammatory cells that degrade the ECM, GF, and cells necessary for wound healing to occur. Cellular and acellular matrix products can be used in the management of a variety of chronic wounds including venous, diabetic, and pressure ulcers and other conditions such as burns, epidermolysis bullosa, pyoderma gangrenosum, and surgical wounds. These matrices provide cells, GF, and other key elements that act as a scaffold and promote reepithelialization and revascularization of the wound bed., Methods: This article focuses on cellular and acellular matrix products that have been well-studied clinically with positive results in randomized clinical trials and widely available matrices for chronic nonhealing wounds. We present trial results as well as their indications, techniques, and outcomes., Results: There are a variety of matrix products available on the market. Some of these products are used to treat chronic wounds, for example, diabetic foot ulcers, venous leg ulcers, pyoderma gangrenosum, and pressure ulcers. In this review, we found that wounds of different etiologies have been treated with a variety of matrices, with successful outcomes compared with standard wound care., Conclusions: Both cellular and acellular matrix products are useful in the management of a variety of chronic wounds. These matrices provide cells, GF, and other key elements that promote reepithelialization and revascularization of the wound bed while preventing degradation of the ECM. The treatment of chronic wounds with matrix products in combination with standard wound care has been proven to aid in wound healing when added to standard of care.

Importance: Patients' perceptions of their physician can affect subjective and objective outcomes. Physician attire influences patients' perceptions of their physician and consequently may affect patient outcomes., Objective: To determine patient preferences for different types of dermatologist attire in dermatology medical, surgical, and wound care clinics. We hypothesized that patients in the dermatology medical setting would prefer professional attire, while patients in the dermatology surgical and wound care setting would prefer surgical scrubs., Design, Setting, and Participants: This study analyzed responses to a cross-sectional, anonymous survey by English-speaking dermatology patients (aged 18 years or older) at general, surgical, and wound care clinics in an academic center in Miami, Florida. Patients who could not read and understand the survey were excluded. Participants received pictures of a physician wearing business attire, professional attire, surgical attire, and casual attire, and responded by indicating which physician they preferred for each of 19 questions. Frequencies of responses were recorded, and χ2 and regression tests were performed., Main Outcomes and Measures: Response frequencies., Results: Surveys were administered to 261 persons, and 255 participated and completed enough of the questions to be included in the outcome analyses (118 men, 121 women, 22 unknown [did not answer sex question]), mean (SD) age, 56.3 (18.6) years; about 49% of those who reported their sex were men; 56% were Hispanic; and 85% were white. Approximately 72% of respondents held a college degree or higher. About 63%, 24%, and 13% of respondents were medical, surgical, and wound care dermatology patients, respectively. Roughly 73%, 19%, 6%, and 2% of cumulative responses were for professional, surgical, business, and casual attire, respectively. Respondents who received a picture of a black male or black female physician were more likely to exclusively prefer professional attire: unadjusted odds ratios (ORs) 3.21 (95% CI, 1.39-7.42) and 2.78 (95% CI, 1.18-6.51), respectively, compared with respondents who received a picture of a white male physician. Nonwhite and unemployed respondents were less likely to prefer professional attire exclusively: ORs, 0.28 (95% CI, 0.1-0.83) and 0.28 (95% CI, 0.08-0.99), respectively. Respondents preferred professional attire in all clinic settings, though respondents in the dermatology surgery clinic were less likely to prefer professional attire compared with respondents in the medical dermatology clinic: race-adjusted OR, 0.74 (95% CI, 0.56-0.98). Wound care and medical dermatology respondents preferred professional attire comparably., Conclusions and Relevance: In this study, most patients preferred professional attire for their dermatologists in most settings. It is possible that patients' perceptions of their physicians' knowledge and skill is influenced by the physicians' appearance, and these perceptions may affect outcomes.

Background: A man in his 60s with recurrent venous leg ulcers (VLUs) presented with an 18-month history of a VLU on his medial left leg measuring 59.3 cm(2). He had been treated with multi- component compression bandages without significant decrease in ulcer size. Given the ulcer's size, refractory nature, and history of recurrence, the authors sought to optimize the patient's healing., Methods: Approximately 23% of the total wound was treated using punch grafts (PGs) harvested from different locations on the body based on hair density using the "stick and place" method., Results: One month later, a 56% reduction in ulcer size was observed, especially in the area that received hair-bearing skin., Conclusion: Punch grafts from hair-bearing skin are a viable source of follicular stem cells and may be superior to PG from nonhair-bearing skin for the treatment of chronic wounds.

Diabetic foot ulcers (DFUs) affect 1.5 million Americans annually, of which only a minority heal with standard care, and they commonly lead to amputation. To improve care, investigations are underway to better understand DFU pathogenesis and develop more effective therapies. Some currently used medications may improve healing. One small, randomized clinical trial found statins improve DFU healing. In this secondary analysis of a large multisite prospective observational cohort of 139 patients with DFUs receiving standard care, we investigated whether there was an association between 6-week DFU wound size reduction and use of a variety of medications including alpha-blockers, beta-blockers, angiotensin converting enzyme inhibitors (ACEi) and statins. We found no significant (p < 0.05) association between six-week wound reduction and use of any of the evaluated drugs; however, statins did trend toward an association (p = 0.057). This suggests a potential benefit of statins on DFU healing, and larger, targeted studies are warranted., (© 2016 by the Wound Healing Society.)

Introduction: Clinical models are invaluable in studying wound healing. Challenges in studying human wounds include heterogeneity of patients and wounds, as well as prolonged study time, resulting in high costs. Animal models are an efficient method to study wound healing, but often lack correlation with human acute wound healing. Human wound models can be created using sharp instruments, suction, acids, heat and cold. In this observational study, we propose a practical human acute wound model where partial thickness wounds are induced by cryosurgery to create wounds that could facilitate wound healing research and development., Methods: On forearms of 8 healthy adult volunteers, freeze injuries were induced using liquid nitrogen spray delivered onto a target area of a 1 cm circular opening at a distance from the cryo-device to the skin of 0.5-1 cm. Several freeze-thaw time cycles were implemented by administering pulses ranging from 3 to 12 seconds. Clinical evaluation was performed at a 24-hour follow-up period. Blister roofs were histologically analyzed by a blinded dermatophathologist. Clinical assessment of time to heal was determined., Results: Freeze-times greater than 5 seconds caused a majority of subjects to develop blisters, and freeze-times greater than 8 seconds resulted in uniform blister formation. Consistent histology of full thickness necrotic epidermis with intact detached basement membrane with minimal acute neutrophilic inflammatory infiltrate was observed in all blister specimens examined. The 8-second freeze-time group had a time to heal of 13-14 days, while the 12-second freeze-time group required 3 weeks to heal. After healing, an area of hypopigmented skin and slightly hypertrophic scarring remained., Discussion: This novel cryo-induced wound model is a potential simple, efficient and reliable model for studying the dynamic processes involved in acute wound healing and to aid in the development of new wound healing therapies. Clinicaltrials.gov identifier: NCT01253135.

Non-healing wounds are associated with an inflammatory and proteolytic wound environment, and recent therapeutic strategies have been focused on reversing these changes. Connexins, as members of gap junctions, are important in intercellular signaling and wound repair. Connexin 43 (Cx43) downregulation is associated with normal wound healing, and it has been found to be upregulated in non-healing venous leg ulcers (VLUs). Ghatnekar et al. (2014) report findings of a small phase II trial performed in Indian patients with chronic VLUs, reporting that ACT1, a mimetic peptide of Cx43, accelerates healing in the treatment group. Despite standard care with compression therapy and adjuvant therapy for refractory wounds, at present in clinical practice a significant number of patients remain unhealed. The potential for ACT1 exists to help heal refractory VLUs, but it faces additional regulatory hurdles.