Malignant melanoma arising in a burn scar.

Secondary malignancies are rare but devastating complications of longstanding burn scars. Squamous cell carcinoma is the most common, followed by basal cell carcinoma and melanomas. There are fewer than 50 total reported cases of malignant melanomas arising in burn scars. We report a case of malignant melanoma arising within a longstanding burn scar confirmed by histology, FISH, and PRAME staining to further characterize melanomas arising in burn scars and to illustrate the diagnostic challenges they present.

Effects of Weight Loss and Aerobic Exercise Training on Adi-Pose Tissue Zinc α2-Glycoprotein and Associated Genes in Obesity.

Zinc α2-glycoprotein (ZAG) has been implicated in fatty acid metabolism and utilization and is lower in obese and higher in cachexic adults compared to those of normal weight. Previous studies suggest that ZAG binds to the beta3-adrenergic receptor (ß3AR) to influence fatty acid metabolism in adipose tissue by regulating hormone sensitive lipase (HSL). The purpose of this study is to investigate the effects of a six-month weight loss (WL) or aerobic exercise (AEX) intervention on adipose tissue and skeletal muscle ZAG mRNA levels and protein expression, as well as the expression of ß3AR, and HSL. Abdominal adipose tissue (AB) and gluteal adipose tissue (Glut) and vastus lateralis muscle biopsies were performed before and after WL (n = 13) or AEX (n = 13). ZAG, HSL, and ß3AR expressions were determined by RT-PCR, and ZAG and HSL plasma levels by ELISA. Body weight decreased by 9.69% (p < 0.001) in WL and did not change with AEX. Maximal oxygen consumption (VO2max) increased by 7.1% (p < 0.005) after WL and by 16.69% (p < 0.001) after AEX. WL significantly decreased body weight with a reduction of percentage of fat, fat mass, fat-free mass (FFM). AEX decreased percent fat and increased VO2max, but did not change fat mass and FFM. Abdominal ZAG and HSL mRNA levels did not change significantly after WL or AEX. There were no changes in plasma ZAG, HSL and adipose tissue ß3AR mRNA levels after WL and AEX. ZAG, HSL and ß3AR mRNA expressions in adipose tissue are positively associated each other. Adipose tissue abdominal and gluteal HSL are negatively associated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), and both ZAG and HSL adipose tissue are negatively associated with fasting glucose and the glucose area under the curve. Further work is needed to elucidate the role of ZAG and HSL in the propensity for weight gain and the ability of exercise to mitigate these responses.

A case of cutaneous Scedosporium apiospermum infection in a patient on a janus kinase inhibitor.

Scedosporium apiospermum is a mold that is usually found in soil and polluted water, but has also been linked to contaminated ambient air in hospitals. This fungus typically behaves as a rare opportunistic pathogen affecting immunocompromised patients in whom disseminated disease can readily occur, causing shock and multiorgan failure. We report the first case of cutaneous Scedosporium apiospermum infection in a patient with rheumatoid arthritis treated with a Janus kinase inhibitor. We also reviewed other cutaneous manifestations of Scedosporium apiospermum reported between 2003 and 2022.

The Importance of Cutaneous Innervation in Wound Healing: From Animal Studies to Clinical Applications.

The skin is a neuroimmunoendocrine organ that regularly undergoes injury and repair. The complex process of wound healing relies heavily on the cutaneous nervous system. Despite the observation that wound healing deficiencies cause significant morbidity and mortality for patients with nervous dysfunction across many disciplinaries, the role of cutaneous innervation in wound repair has not been well elucidated. In a previous article, we learned the basics of cutaneous neuroanatomy and the important neuropeptides involved in the wound healing process. Currently, we aim to synthesize the basics with observations from animal models and human studies for a more comprehensive understanding of nervous system involvement in cutaneous wound healing. We have demonstrated in this review, the importance of the cutaneous nervous system in each phase of wound healing through basic science research, animal experiments, and human studies.

Wound Closure with Transcutaneous Absorbable Polyglactin Sutures after Hidradenitis Suppurativa Excision.

OBJECTIVE: Wide surgical excision is the standard treatment for severe hidradenitis suppurativa (HS). Because of the nature of HS, these wounds are often nonsterile, located in moist intertriginous regions, and closed under tension, increasing the risk for surgical site complications. Although uncommon, absorbable sutures may confer benefits over nonabsorbable material for skin closure. Accordingly, the authors evaluated the use of absorbable, braided, transcutaneous polyglactin sutures after wide surgical excision of HS. METHODS: The authors performed a retrospective chart review for all consecutive patients who underwent wide surgical excision of HS at a tertiary university hospital between January 2009 and March 2020. RESULTS: Sixty consecutive patients with 174 operative sites were included in the study. The surgical site complication rate was 17.8%. Postoperative complications included wound dehiscence (n = 18), surgical site infection (n = 2), and scar contracture (n = 1). Sutures were removed from 12 (6.9%) operative sites. Factors influencing complications were Hurley grade and area of excision. Complications did not differ significantly among disease locations (P = .6417). CONCLUSIONS: The results support the growing evidence that absorbable sutures are an appropriate option after wide surgical excision of HS.

Scurvy: A Diagnosis Not to Be Missed.

Vitamin C deficiency, one of the oldest-known nutritional disorders, is now uncommon in high-income countries. Recently, however, there has been an increase in cases of vitamin C deficiency, also known as scurvy. We report three adult patients with histories of homelessness, food insecurity, and poor nutrition, making them particularly vulnerable to restrictive diets and at increased risk for scurvy. After proper diagnosis and treatment, favorable outcomes can be rapidly obtained. This case series emphasizes the importance of keeping a broad differential diagnosis and inquiring about nutritional history in patients presenting with purpura, gingival bleeding, and body hair changes.

Neuroanatomy of the Cutaneous Nervous System Regarding Wound Healing.

Wound healing is an important topic in modern medicine across many disciplines. Healing of all cutaneous wounds, whether accidentally sustained or intentionally created, requires the common yet complex set of interactions between the immune, circulatory, nervous, endocrine, and integumentary systems. Deficits in any of these systems or the molecular factors that mediate their communications can contribute to impaired healing of cutaneous wounds. While the stages of wound repair, angiogenesis, growth factors, and cytokines involved have been extensively studied, the role of the cutaneous nervous system in wound healing has not been well outlined. We have provided a basic overview of cutaneous innervation and wound repair for the dermatologic surgeon by outlining the normal cutaneous nervous anatomy and function and discussing the most important neuropeptides that mediate the wound healing process.

Pediatric sweet syndrome.

Pediatric Sweet syndrome is a rare dermatosis often triggered by a prodromal illness or infection and characterized histologically by a dense neutrophilic infiltrate. We report a 2-year-old girl with a classic presentation of Sweet syndrome following an acute thumb paronychia, who had a negative history of malignancy or immunodeficiency.

Follow the money: Investigating gender disparity in industry payments among senior academics and leaders in plastic surgery.

INTRODUCTION: Differences in academic qualifications are cited as the reason behind the documented gender gap in industry sponsorship to academic plastic surgeons. Gendered imbalances in academic metrics narrow among senior academic plastic surgeons. However, it is unknown whether this gender parity translates to industry payments. METHODS: We conducted a cross-sectional analysis of industry payments disbursed to plastic surgeons in 2018. Inclusion criteria encompassed (i) faculty with the rank of professor or a departmental leadership position. Exclusion criteria included faculty (i) who belonged to a speciality besides plastic surgery; (ii) whose gender could not be determined; or (iii) whose name could not be located on the Open Payment Database. Faculty and title were identified using departmental listings of ACGME plastic surgery residency programs. We extracted industry payment data through the Open Payment Database. We also collected details on H-index and time in practice. Statistical analysis included odds ratios (OR) and Pearson's correlation coefficient (R). RESULTS: We identified 316 senior academic plastic surgeons. The cohort was predominately male (88%) and 91% held a leadership role. Among departmental leaders, women were more likely to be an assistant professor (OR 3.9, p = 0.0003) and heads of subdivision (OR 2.1, p = 0.0382) than men. Industry payments were distributed equally to male and female senior plastic surgeons except for speakerships where women received smaller amounts compared to their male counterparts (median payments of $3,675 vs $7,134 for women and men respectively, p<0.0001). Career length and H-index were positively associated with dollar value of total industry payments (R = 0.17, p = 0.0291, and R = 0.14, p = 0.0405, respectively). CONCLUSION: Disparity in industry funding narrows at senior levels in academic plastic surgery. At higher academic levels, industry sponsorship may preferentially fund individuals based on academic productivity and career length. Increased transparency in selection criteria for speakerships is warranted.

Idebenone Has Distinct Effects on Mitochondrial Respiration in Cortical Astrocytes Compared to Cortical Neurons Due to Differential NQO1 Activity.

Idebenone is a synthetic quinone that on reduction in cells can bypass mitochondrial Complex I defects by donating electrons to Complex III. The drug is used clinically to treat the Complex I disease Leber's hereditary optic neuropathy (LHON), but has been less successful in clinical trials for other neurodegenerative diseases. NAD(P)H:quinone oxidoreductase 1 (NQO1) appears to be the main intracellular enzyme catalyzing idebenone reduction. However, NQO1 is not universally expressed by cells of the brain. Using primary rat cortical cells pooled from both sexes, we tested the hypotheses that the level of endogenous NQO1 activity limits the ability of neurons, but not astrocytes, to use idebenone as an electron donor to support mitochondrial respiration. We then tested the prediction that NQO1 induction by pharmacological activation of the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) enables idebenone to bypass Complex I in cells with poor NQO1 expression. We found that idebenone stimulated respiration by astrocytes but reduced the respiratory capacity of neurons. Importantly, idebenone supported mitochondrial oxygen consumption in the presence of a Complex I inhibitor in astrocytes but not neurons, and this ability was reversed by inhibiting NQO1. Conversely, recombinant NQO1 delivery to neurons prevented respiratory impairment and conferred Complex I bypass activity. Nrf2 activators failed to increase NQO1 in neurons, but carnosic acid induced NQO1 in COS-7 cells that expressed little endogenous enzyme. Carnosic acid-idebenone combination treatment promoted NQO1-dependent Complex I bypass activity in these cells. Thus, combination drug strategies targeting NQO1 may promote the repurposing of idebenone for additional disorders.SIGNIFICANCE STATEMENT Idebenone is used clinically to treat loss of visual acuity in Leber's hereditary optic neuropathy. Clinical trials for several additional diseases have failed. This study demonstrates a fundamental difference in the way idebenone affects mitochondrial respiration in cortical neurons compared with cortical astrocytes. Cortical neurons are unable to use idebenone as a direct mitochondrial electron donor due to NQO1 deficiency. Our results suggest that idebenone behaves as an NQO1-dependent prodrug, raising the possibility that lack of neuronal NQO1 activity has contributed to the limited efficacy of idebenone in neurodegenerative disease treatment. Combination therapy with drugs able to safely induce NQO1 in neurons, as well as other brain cell types, may be able to unlock the neuroprotective therapeutic potential of idebenone or related quinones.

Reconstruction for axillary hidradenitis suppurativa using one-stage local tissue rearrangement: A retrospective analysis of 53 cases.

Wide local excision offers a potential cure for severe axillary hidradenitis suppurativa. However, the gold standard for reconstruction has yet to be defined. Here, we describe our rotation advancement flap technique, which allows for one-stage closure of large axillary defects, with minimal functional morbidity to the axilla. We performed a retrospective review of all patients who underwent one-stage surgical management for axillary hidradenitis suppurativa at a single-centre tertiary care hospital from 2009 to 2018. We identified 34 patients, with a total of 53 operative sites. The majority were female (85%) with a mean age of 31 years and body mass index 35 kg/m2 . The median defect size was 84 cm2 and the majority were treated using the rotation advancement flap technique (86%). A quarter of operative sites experienced minor complications with only one requiring re-operation. At a median follow-up of 32 months, two (4%) sites showed decreased range of motion. However, all patients had achieved remission without any further recurrence of disease. We describe a one-stage rotation advancement flap technique for management of moderate to severe hidradenitis suppurativa that achieves a high local cure rate, minimal functional morbidity, and acceptable wound complication rates.

Trends in the Academic Credentials of Matched Dermatology Residency Applicants.

Introduction Research can be used to enhance the competitiveness of an application and is associated with a successful match. However, current reports regarding the publication record among prospective dermatology residents may be inaccurate. We sought to accurately assess the research credentials of matched dermatology residency candidates at the time of application. Methods We performed a bibliometric analysis to identify published articles of 1152 matched dermatology candidates and calculated the h-index of each applicant at the time of application. Details on article type, first authorship, and dermatology-relatedness of articles were collected. Results The median number of publications was two and the median h-index was 0. At the time of residency application, one-quarter of matched dermatology candidates (24%, n=278) possessed no publications. Over time, the median number of publications (R 0.10, p<0.001) and h-index (R 0.07, p=0.014) of matched applicants increased. The proportion of first-authored articles, dermatology-related papers, and each article type remained constant across application cycles (p>0.0500). An additional graduate degree, completion of a research fellowship, and graduation from a non-US medical school were independently associated with greater research credentials (p<0.0500). Conclusions Each year, applicants are publishing more articles and have a greater scholarly impact than in previous application cycles. However, the verified publication volume of matched dermatology applicants is strikingly lower than the values reported in national statistics.

Atypical Mycobacterial Infections After Plastic Surgery Procedures Abroad: A Multidisciplinary Algorithm for Diagnosis and Treatment.

BACKGROUND: The recent rise in medical tourism, especially for cosmetic procedures, has been mirrored by an increase in the incidence of infections with Mycobacterium abscessus, which is an atypical mycobacterium that is ubiquitous in aquatic environments. M. abscessus soft tissue infections arise from the use of improperly sterilized water and surgical equipment during surgical procedures, and these infections have devastating consequences if not promptly treated. M. abscessus infections are notoriously difficult to diagnose and properly treat, and therefore, we illustrate a typical case presentation and provide a comprehensive diagnostic and treatment algorithm. METHODS: Of the patients who have presented to our hospital for treatment of cutaneous M. abscessus infections, a representative patient's story was included to illustrate the typical presentation and treatment timeline. The current literature on M. abscessus infections was reviewed, and this literature and the clinical experience of our plastic surgery and infectious disease teams were used in the creation of a diagnostic and treatment algorithm for M. abscessus infections. RESULTS: M. abscessus infections can have an incubation period of months, and the classic presenting signs include purulent drainage, violaceous nodules, and subcutaneous abscesses at the site of a recent surgery. A key finding is persistence of the infection despite debridement and empiric antibiotic treatment. Cultures grown on mycobacterial-specific growth media are considered the diagnostic criterion standard, but high clinical suspicion is enough to warrant the initiation of treatment. Treatment itself consists of surgical drainage and debridement in combination with multidrug antibiotic regimens that typically include amikacin, a macrolide, and a carbapenem or cephalosporin antibiotic, with the option for macrolide and fluoroquinolone maintenance therapy. CONCLUSIONS: M. abscessus cutaneous infections present with unique history and physical examination findings and often require complex diagnostic workups and treatment plans. Increased provider awareness of the management and potential complications of M. abscessus is crucial to the improvement patient outcomes, as is a multidisciplinary approach that incorporates primary care providers, pathologists, plastic surgeons, and infectious disease specialists.

Factors influencing the local cure rate of hidradenitis suppurativa following wide local excision.

Wide local excision is the gold standard and only potential curative therapy for recalcitrant hidradenitis suppurativa. However, high recurrence rates persist even post-surgery with little known on the influencing factors for remission. We evaluated the effect of patient, disease, and operative factors on local cure rate of moderate to severe hidradenitis following wide local excision. We performed a retrospective chart review for all patients who had undergone surgical excision of hidradenitis at a university hospital from 2012 to 2018. We identified 79 patients with a total of 220 operative sites. The majority were obese (mean body mass index [BMI] 32.5), female (71%), African-American (84%), and had a mean age of 31 years. A quarter of operative sites experienced a recurrence (n = 56). Patients who achieved remission had a significantly lower number of affected regions than those who experienced a recurrence (2.3 vs 3.6, P = .0023). Additionally, recurrence rate differed significantly between body locations (P = .0440). Smoking, BMI, Hurley grade, closure method, and excision size did not influence local cure rate. Surgical excision remains a worthy management option for hidradenitis patients with three quarters achieving remission after a single operation. Number of affected regions and location of hidradenitis may play a factor in recurrence.

Sex Disparity in Academic Rank and Industry Payments to Plastic Surgeons.

INTRODUCTION: Despite increasing representation in surgery, women continue to lag behind men in important metrics. Little is known on how industry funding may also contribute to this ongoing disparity. This article seeks to quantify industry payments to academic plastic surgeons (APSs) by sex and examine the relationship between funding and academic achievement. METHODS: We conducted a cross-sectional analysis of industry payments disbursed to APSs in 2017. Faculty were identified using departmental listings of Accreditation Council for Graduate Medical Education plastic surgery residency programs. Payments were identified via the Center for Medicare and Medicaid Services open payment database. Academic achievement was assessed using rank (eg, assistant professor), leadership designation (eg, division head), and Scopus H-index and then controlled for time in practice. RESULTS: Of the 805 APSs, the majority were male (82% male vs 18% female, P < 0.0001). Significant sex differences emerged in average yearly industry contributions (men, US $3202, vs women, US $707; P < 0.0001). Across all academic ranks, men received significantly higher payments than women (P < 0.0500). Men constituted 93% of full professors and were almost twice as likely to hold additional leadership positions compared with women (odds ratio, 1.82; P = 0.0143). After adjustment for time in practice, there was no difference in H-indices between male and female APSs, although payment disparity persisted (P < 0.0001). CONCLUSIONS: Substantial sex-based disparities exist among APSs' academic rank and leadership attainment, which is not attributed to differences in academic qualifications or experience. To better elucidate the sources of this disparity, future studies should assess sexed differences in payment types. Furthermore, we urge for increased transparency in the selection process for industry payments.

Serum level of advanced oxidation protein products (AOPPs) in patients with Henoch-Schonlein purpura and its relationship with aberrant glycosylation of IgA1 and Cosmc mRNA expression.

BACKGROUND: Henoch-Schonlein purpura (HSP) is a systemic small vessel vasculitis that is mainly caused by IgA1-type immune complex deposition. Advanced oxidation protein products (AOPPs) are specific markers of protein oxidation. OBJECTIVE: To explore the role of AOPPs in the pathogenesis of HSP. METHODS: There are 51 HSP patients who were divided into four subgroups: (i) skin type - 20 cases; (ii) joint type - 8 cases; (iii) abdominal type - 12 cases; (iv) renal type - 11 cases; and 18 healthy volunteers were enrolled as controls. The serum levels of AOPPs and Gd-IgA1 were quantified by an HAA-lectin-based ELISA. The Cosmc mRNA expression in peripheral B lymphocytes was measured by RT-PCR. RESULTS: 1. Advanced oxidation protein products in different subgroups of HSP patients are all higher than the controls, while the renal-type subgroup is the highest and the skin-type subgroup is the lowest. 2. Spearman correlation analysis shows that: (i) AOPPs and Gd-IgA1 in HSP patients are positively correlated; both of them are positively correlated with the disease severity scores; (ii) AOPPs are negatively correlated with the relative expression value (RQ) of Cosmc mRNA. CONCLUSION: Advanced oxidation protein products play an important role in the pathogenesis of HSP, especially in renal-type patients.

Negative Pressure Wound Therapy with Instillation and Dwell Time in the Surgical Management of Severe Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a physically debilitating disease that greatly impairs the quality of life of affected individuals. Advanced disease is often difficult to treat with topical and systemic therapies. Surgical resection of diseased skin has become paramount in HS management but proposes challenges of wound care and closure. METHODS: Four patients with a total of 12 complex wounds were treated over a three year period. All of the patients were males between the ages of 28 and 61 years. The lesions were located on the buttocks (n=5), chest (n=1), perianal (n=2), perineal (n=2), and axillary regions (n=2). A protocol of wide local excision, followed by negative pressure wound therapy with instillation and dwell time (NPWTi-d) to decrease bioburden and promote angiogenesis of the exposed base, and subsequent skin grafting was used. Patients remained hospitalized between procedures. RESULTS: The original wound area ranged from 210-540 cm2. Skin grafts of comparable sizes were taken from donor sites. The average duration of NPWTi-d placement was 3.5 days and the average time from excision to wound coverage was 4.3 days. The percent of graft uptake ranged from 70%-90%. All patients were resolved of their local disease with no complications. CONCLUSIONS: Surgical management of HS can be complicated by difficult closures. This case series demonstrates that wide local excision followed by NPWTi-d and skin grafting is able to achieve local resolution of disease in HS patients who have failed multiple minimally invasive therapies.

The Putative Drp1 Inhibitor mdivi-1 Is a Reversible Mitochondrial Complex I Inhibitor that Modulates Reactive Oxygen Species.

Mitochondrial fission mediated by the GTPase dynamin-related protein 1 (Drp1) is an attractive drug target in numerous maladies that range from heart disease to neurodegenerative disorders. The compound mdivi-1 is widely reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate brain injury. Here, we show that mdivi-1 reversibly inhibits mitochondrial complex I-dependent O2 consumption and reverse electron transfer-mediated reactive oxygen species (ROS) production at concentrations (e.g., 50 µM) used to target mitochondrial fission. Respiratory inhibition is rescued by bypassing complex I using yeast NADH dehydrogenase Ndi1. Unexpectedly, respiratory impairment by mdivi-1 occurs without mitochondrial elongation, is not mimicked by Drp1 deletion, and is observed in Drp1-deficient fibroblasts. In addition, mdivi-1 poorly inhibits recombinant Drp1 GTPase activity (Ki > 1.2 mM). Overall, these results suggest that mdivi-1 is not a specific Drp1 inhibitor. The ability of mdivi-1 to reversibly inhibit complex I and modify mitochondrial ROS production may contribute to effects observed in disease models.

Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein.

Ubiquitin- and proteasome-dependent outer mitochondrial membrane (OMM)-associated degradation (OMMAD) is critical for mitochondrial and cellular homeostasis. However, the scope and molecular mechanisms of the OMMAD pathways are still not well understood. We report that the OMM-associated E3 ubiquitin ligase MARCH5 controls dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and cell sensitivity to stress-induced apoptosis. MARCH5 knockout selectively inhibited ubiquitination and proteasomal degradation of MiD49, a mitochondrial receptor of Drp1, and consequently led to mitochondrial fragmentation. Mitochondrial fragmentation in MARCH5(-/-) cells was not associated with inhibition of mitochondrial fusion or bioenergetic defects, supporting the possibility that MARCH5 is a negative regulator of mitochondrial fission. Both MARCH5 re-expression and MiD49 knockout in MARCH5(-/-) cells reversed mitochondrial fragmentation and reduced sensitivity to stress-induced apoptosis. These findings and data showing MARCH5-dependent degradation of MiD49 upon stress support the possibility that MARCH5 regulation of MiD49 is a novel mechanism controlling mitochondrial fission and, consequently, the cellular response to stress.