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ImportancePatient-perceived barriers to hidradenitis suppurativa (HS) care are poorly understood. Understanding health care barriers is a critical first step toward improving care for this population.ObjectiveTo characterize the health care experiences of people living with HS, including perceived barriers and facilitators to health care access, and to elucidate potential associations among these barriers and facilitators, health care access, and disease activity.Design, Setting, and ParticipantsIn this qualitative study, an inductive thematic analysis was conducted on 45 in-depth, 60- to 90-minute semistructured interviews of 45 people with HS from diverse sociodemographic backgrounds that took place between March and April 2020. Individuals were eligible if they could speak English, were 18 years or older, and were diagnosed with HS. A diagnosis of HS was confirmed through physician diagnosis or through self-reported, affirmative response to the validated screening question, “Do you experience boils in your armpits or groin that recur at least every six months?”Main Outcomes and MeasuresInterviews were audio recorded and transcribed verbatim. A modified grounded theory approach was used to develop the codebook, which investigators used for inductive thematic analysis.ResultsAmong the 45 participants included, the median (IQR) age was 37 (16) years, 33 (73%) were female, and 22 (49%) were White. There were 6 interrelated themes associated with participant-perceived barriers to accessing HS care: (1) bidirectional associations of disease activity and employment, (2) association of employment with health care coverage, (3) association of health care coverage with costs and perceived access to care, (4) association of costs with access to patient-centered care, (5) health care professional attitudes and knowledge influence patient-centered care and perceived access to care and disease activity, and (6) health system characteristics influence patient-centered care and associated costs, perceived access to care, and disease activity.Conclusions and RelevanceThis qualitative study highlights themes that generate a conceptual model for understanding barriers that may act synergistically to limit health care access and influence disease activity. The disease activity of HS may be reduced when cycle elements are optimized. This study also highlights areas for future investigations and potential systems-level changes to improve access to patient-centered HS care.

The literature on hidradenitis suppurativa (HS) in sexual and gender minorities (SGM) remains sparse. This review article aims to discuss critical factors for providers to consider in LGBTQIA patients with HS, including associated comorbidities, gender-affirming hormonal therapy, squamous cell carcinoma, infections in HIV-positive patients, and creating a welcoming clinic for SGM patients.

Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti–human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.

Background Exposure to ultraviolet radiation (UVR) is the major modifiable risk factor for skin cancers. The majority of lifetime UVR exposure occurs before age 20, underscoring an important window for risk reduction. Incorporation of skills-based sunscreen education into school health curricula may foster the development of consistent and effective use of sunscreen among children and youth. We describe the study protocol for a first-of-its-kind study that examined the feasibility of bringing skills-based sunscreen education into kindergarten classrooms. Methods Participants were 96 kindergarten students across four classrooms in a single elementary school. A single-blind open-label trial design was used to evaluate the feasibility of incorporating a song-based, video-guided intervention for independent application of sunscreen into the kindergarten curriculum. Students first completed a 10-day no-intervention baseline period, followed by a 10-day intervention period, and then a 10-day randomized follow-up period where students were randomly assigned to continue with the intervention or to revert to the no-intervention condition. Outcomes Feasibility metrics associated with study process, resources, management, scientific outcomes and safety were gathered. The primary outcome was pre-to-post intervention changes in student engagement in the sunscreen task. The secondary outcome was pre-to-post intervention changes in the proportion of exposed skin to which a student applies sunscreen. Teacher and student perceptions of intervention value and utility were also evaluated. Discussion This is the study protocol for a clinical trial designed to determine the feasibility of implementing a skills-based sunscreen curriculum in kindergarten classrooms. Next steps include evaluation of the intervention for efficacy and effectiveness. Clinical Trial Registration: NCT03752736

Pachydermodactyly (PDD) is a rare, benign condition characterized by swelling and thickening of the periarticular skin, most commonly at the proximal interphalangeal joints. Diagnosis is routinely made through correlation of clinical, histopathologic, and radiographic findings. Here, we report a case of PDD in a 25-year-old male, with emphasis on the clinical and histopathologic differential diagnosis and potential diagnostic pitfalls.

Summary Background Postoperative complication following ventral hernia repair (VHR) is a major clinical and financial burden. Preoperative risk assessment is necessary to minimize adverse outcomes following VHR. This study examines the ability of an independent parameter to predict postoperative morbidity following VHR. Methods A retrospective analysis of 58 patients who underwent VHR by component separation between January 2009 and December 2013 was performed. Preoperative abdominal CT scans were analyzed to assess sarcopenia. Sarcopenia was determined using the Hounsfield unit average calculation (HUAC), a measure of psoas muscle size and density. Sarcopenia was defined as an HUAC score of less than 19.6 HU calculated using receiver operating characteristic (ROC) analysis and the Youden index. Multivariate analysis was performed to analyze the association of sarcopenia and postoperative complications. Results Preoperative sarcopenia was associated with an increased risk for postoperative complications (odds ratio [OR] = 5.3; p = 0.04). Preexisting gastrointestinal conditions such as ulcerative colitis or colon cancer were associated with an increased risk for postoperative complications (OR = 5.7; p = 0.05). A significantly higher rate of hernia recurrence (33.3% vs. 10.8% [p = 0.04]) and renal failure (19% vs. 2.7% [p = 0.03]) was noted in patients with sarcopenia when compared to patients without sarcopenia. Conclusions Sarcopenia is an independent risk factor for postoperative complications in patients who underwent VHR. Assessment of sarcopenia using the HUAC score provides an opportunity for the adjustment of perioperative care plans to minimize postoperative complication rates.

Significance: Scarring of the skin from burns, surgery, and injury constitutes a major burden on the healthcare system. Patients affected by major scars, particularly children, suffer from long-term functional and psychological problems. Recent Advances: Scarring in humans is the end result of the wound healing process, which has evolved to rapidly repair injuries. Wound healing and scar formation are well described on the cellular and molecular levels, but truly effective molecular or cell-based antiscarring treatments still do not exist. Recent discoveries have clarified the role of skin stem cells and fibroblasts in the regeneration of injuries and formation of scar. Critical Issues: It will be important to show that new advances in the stem cell and fibroblast biology of scarring can be translated into therapies that prevent and reduce scarring in humans without major side effects. Future Directions: Novel therapies involving the use of purified human cells as well as agents that target specific cells...

Significance: Excessive scarring is major clinical and financial burden in the United States. Improved therapies are necessary to reduce scarring, especially in patients affected by hypertrophic and keloid scars. Recent Advances: Advances in our understanding of mechanical forces in the wound environment enable us to target mechanical forces to minimize scar formation. Fetal wounds experience much lower resting stress when compared with adult wounds, and they heal without scars. Therapies that modulate mechanical forces in the wound environment are able to reduce scar size. Critical Issues: Increased mechanical stresses in the wound environment induce hypertrophic scarring via activation of mechanotransduction pathways. Mechanical stimulation modulates integrin, Wingless-type, protein kinase B, and focal adhesion kinase, resulting in cell proliferation and, ultimately, fibrosis. Therefore, the development of therapies that reduce mechanical forces in the wound environment would decrease the risk of developing excessive scars. Future Directions: The development of novel mechanotherapies is necessary to minimize scar formation and advance adult wound healing toward the scarless ideal. Mechanotransduction pathways are potential targets to reduce excessive scar formation, and thus, continued studies on therapies that utilize mechanical offloading and mechanomodulation are needed.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053–4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.

Background:. Abdominoperineal resection (APR) carries a high risk of morbidity. Preoperative risk assessment can help with patient counseling, minimize adverse outcomes, and guide surgeons in their choice of reconstruction. This study examined the impact of sarcopenia (low lean muscle mass) on postoperative complications after APR. Methods:. One hundred seventy-eight patients who underwent APR between May 2000 and July 2017 were retrospectively analyzed. Sarcopenia was identified on preoperative computed tomography scans using the Hounsfield Unit Average Calculation. Two cohorts were compared (group 1: primary perineal closure; group 2: flap-based perineal reconstruction). Multivariable analysis evaluated predictors of complications. Results:. Sarcopenia was an independent risk factor for postoperative surgical site infection in patients undergoing APR (odds ratio [OR] = 2.9, P = 0.04). The risk for sarcopenic patients who underwent flap-based perineal reconstruction was even higher (OR = 8.9, P < 0.01). Male sex was also found to be a risk factor for infection (OR = 3.5, P < 0.01). Perineal flap-based reconstruction was a risk factor for delayed wound healing (OR = 3.2, P < 0.01). Conclusions:. Sarcopenia was an independent risk factor for infection in patients undergoing APR. This risk was even greater in patients undergoing flap-based perineal reconstruction. Sarcopenia can be identified on preoperative imaging and inform surgeons on risk stratification and surgical plan.

Sanativo is an over-the-counter Brazilian product derived from Amazon rainforest plant extract that is purported to improve the healing of skin wounds. Two experimental studies have shown accelerated closure of nonsplinted excisional wounds in rat models. However, these models allow for significant contraction of the wound and do not approximate healing in the tight skin of humans.Full-thickness excisional wounds were created on the dorsal skin of mice and were splinted with silicone rings, a model that forces the wound to heal by granulation and reepithelialization. Sanativo or a control solution was applied either daily or every other day to the wounds. Photographs were taken every other day, and the degree of reepithelialization of the wounds was determined.With both daily and every-other-day applications, Sanativo delayed reepithelialization of the wounds. Average time to complete healing was faster with control solution versus Sanativo in the daily application group (9.4 versus 15.2 days; p0.0001) and the every-other-day application group (11 versus 13 days; p = 0.017). The size of visible scar at the last time point of the study was not significantly different between the groups, and no differences were found on histologic examination.Sanativo wound healing compound delayed wound reepithelialization in a mouse splinted excisional wound model that approximates human wound healing. The size of visible scar after complete healing was not improved with the application of Sanativo. These results should cast doubt on claims that this product can improve wound healing in humans.

Surgical manipulation of skin may result in undesired puckering of excess tissue, which is generally assumed to settle over time. In this article, the authors address the novel question of how this excess tissue remodels.Purse-string sutures (6-0 nylon) were placed at the midline dorsum of 22 wild-type BALB/c mice in a circular pattern marked with tattoo ink. Sutures were cinched and tied under tension in the treatment group, creating an excess tissue deformity, whereas control group sutures were tied without tension. After 2 or 4 weeks, sutures were removed. The area of tattooed skin was measured up to 56 days after suture removal. Histologic analysis was performed on samples harvested 14 days after suture removal.The majority of excess tissue deformities flattened within 2 days after suture removal. However, the sutured skin in the treatment group decreased in area by an average of 18 percent from baseline (n = 9), compared to a 1 percent increase in the control group (n = 10) at 14 days after suture removal (p0.05). This was similarly observed at 28 days (treatment, -11.7 percent; control, 4.5 percent; n = 5; p = 0.0243). Despite flattening, deformation with purse-string suture correlated with increased collagen content of skin, in addition to increased numbers of myofibroblasts. Change in area did not correlate with duration of suture placement.Excess dermal tissue deformities demonstrate the ability to remodel with gross flattening of the skin, increased collagen deposition, and incomplete reexpansion to baseline area. Further studies will reveal whether our findings in this mouse model translate to humans.

From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal adhesion kinase).

This study characterizes sex and racial/ethnic discrepancies in exposure to dermatology among US medical students.

OBJECTIVE: To investigate the effects of local doxycycline administration on skin scarring. BACKGROUND: Skin scarring represents a major source of morbidity for surgical patients. Doxycycline, a tetracycline antibiotic with off-target effects on the extracellular matrix, has demonstrated antifibrotic effects in multiple organs. However, doxycycline’s potential effects on skin scarring have not been explored in vivo. METHODS: Female C57BL/6J mice underwent dorsal wounding following an established splinted excisional skin wounding model. Doxycycline was administered by local injection into the wound base following injury. Wounds were harvested upon complete wound closure (postoperative day 15) for histological examination and biomechanical testing of scar tissue. RESULTS: A one-time dose of 3.90mM doxycycline (2mg/mL) within 12 hours of injury was found to significantly reduce scar thickness by 24.8% (*P < 0.0001) without compromising tensile strength. The same effect could not be achieved by oral dosing. In doxycycline-treated scar matrices, collagen I content was significantly reduced (*P = 0.0317) and fibers were favorably arranged with significantly increased fiber randomness (*P = 0.0115). Common culprits of altered wound healing mechanics, including angiogenesis and inflammation, were not impacted by doxycycline treatment. However, engrailed1 profibrotic fibroblasts, responsible for scar extracellular matrix deposition, were significantly reduced with doxycycline treatment (*P = 0.0005). CONCLUSIONS: Due to the substantial improvement in skin scarring and well-established clinical safety profile, locally administered doxycycline represents a promising vulnerary agent. As such, we favor rapid translation to human patients as an antiscarring therapy.

Since the discovery of scarless fetal skin wound healing, research in the field has expanded significantly with the hopes of advancing the finding to adult human patients. There are several differences between fetal and adult skin that have been exploited to facilitate scarless healing in adults including growth factors, cytokines, and extracellular matrix substitutes. However, no one therapy, pathway, or cell subtype is sufficient to support scarless wound healing in adult skin. More recently, products that contain or mimic fetal and adult uninjured dermis were introduced to the wound healing market with promising clinical outcomes. Through our review of the major experimental targets of fetal wound healing, we hope to encourage research in areas that may have a significant clinical impact. Additionally, we will investigate therapies currently in clinical use and evaluate whether they represent a legitimate advance in regenerative medicine or a vulnerary agent. WIREs Dev Biol 2018, 7:e309. doi: 10.1002/wdev.309 This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Plant Development > Cell Growth and Differentiation Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells.

The monocyte lineage is essential to normal wound healing. Macrophage inhibition or knockout in mice results in impaired wound healing through reduced neovascularization, granulation tissue formation, and reepithelialization. Numerous studies have either depleted macrophages or reduced their activity in the context of wound healing. Here, we demonstrate that by increasing the number of macrophages or monocytes in the wound site above physiologic levels via pullulan-collagen composite dermal hydrogel scaffold delivery, the rate of wound healing can be significantly accelerated in both wild-type and diabetic mice, with no adverse effect on the quality of repair. Macrophages transplanted onto wounds differentiate into M1 and M2 phenotypes of different proportions at various time points, ultimately increasing angiogenesis. Given that monocytes can be readily isolated from peripheral blood without in vitro manipulation, these findings hold promise for translational medicine aimed at accelerating wound healing across a broad spectrum of diseases.

SUMMARY Fibroblast heterogeneity has been shown within the unwounded mouse dorsal dermis, with fibroblast subpopulations being identified according to anatomical location and embryonic lineage. Using lineage tracing, we demonstrate that paired related homeobox 1 (Prrx1)-expressing fibroblasts are responsible for acute and chronic fibroses in the ventral dermis. Single-cell transcriptomics further corroborated the inherent fibrotic characteristics of Prrx1 fibroblasts during wound repair. In summary, we identify and characterize a fibroblast subpopulation in the mouse ventral dermis with intrinsic scar-forming potential., In Brief Fibroblasts in the mouse dermis are heterogeneous, but it is unclear which subpopulation contributes to ventral scarring. Using lineage tracing and single-cell transcriptomics, Leavitt et al. report that Prrx1-expressing fibroblasts are largely responsible for fibrosis in the ventral dermis during wound repair., Graphical Abstract

Invasive cancers, major injuries, and infection can cause bone defects that are too large to be reconstructed with preexisting bone from the patient's own body. The ability to grow bone de novo using a patient's own cells would allow bony defects to be filled with adequate tissue without the morbidity of harvesting native bone. There is interest in the use of adipose-derived stromal cells (ASCs) as a source for tissue engineering because these are obtained from an abundant source: the patient's own adipose tissue. However, ASCs are a heterogeneous population and some subpopulations may be more effective in this application than others. Isolation of the most osteogenic population of ASCs could improve the efficiency and effectiveness of a bone engineering process. In this protocol, ASCs are obtained from subcutaneous fat tissue from a human donor. The subpopulation of ASCs expressing the marker BMPR-IB is isolated using FACS. These cells are then applied to an in vivo calvarial defect healing assay and are found to have improved osteogenic regenerative potential compared with unsorted cells.

Abdominal adhesions consist of fibrotic tissue that forms in the peritoneal space in response to an inflammatory insult, typically surgery or intraabdominal infection. The precise mechanisms underlying adhesion formation are poorly understood. Many compounds and physical barriers have been tested for their ability to prevent adhesions after surgery with varying levels of success. The mouse and rat are important models for the study of abdominal adhesions. Several different techniques for the creation of adhesions in the mouse and rat exist in the literature. Here we describe a protocol utilizing abrasion of the cecum with sandpaper and sutures placed in the right abdominal sidewall. The mouse is anesthetized and the abdomen is prepped. A midline laparotomy is created and the cecum is identified. Sandpaper is used to gently abrade the surface of the cecum. Next, several figure-of-eight sutures are placed into the peritoneum of the right abdominal sidewall. The abdominal cavity is irrigated, a small amount of starch is applied, and the incision is closed. We have found that this technique produces the most consistent adhesions with the lowest mortality rate.

Background/Purpose This study examined the effects of multidisciplinary prenatal care and delivery mode on gastroschisis outcomes, with adjustment for key confounding variables. Methods This retrospective cohort study included all gastroschisis patients treated at a single tertiary children's hospital between 1999 and 2009. Prenatal care, delivery mode (vaginal vs cesarean section before labor vs after labor), patient characteristics, and clinical outcomes were determined by chart review. Time to discontinuation of parenteral nutrition (PN) was the primary outcome of interest. Effects of multidisciplinary prenatal care and delivery mode were evaluated using Cox proportional hazards regression models that included gestational age, birth weight, sex, concomitant intestinal complications, and year of admission. Results Of 167 patients included, 46% were delivered vaginally, 69% received multidisciplinary prenatal care, and median time to PN discontinuation was 38 days. On multivariable modeling, gestational age, uncomplicated gastroschisis, and year of admission were significant predictors of early PN independence. Delivery mode and prenatal care had no independent effect on outcomes, although patients receiving multidisciplinary prenatal care were more likely to be born at term (49% vs 27%, P = .01). Conclusions Gestational age and intestinal complications are the major determinants of outcome in gastroschisis. Multidisciplinary prenatal care may facilitate term delivery.

Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based thera- peutics. Stem cells promise improved therapies for healing chronic wounds, but further studies