Interpolation Flaps in the Outpatient Mohs Surgery Setting: A Prospective Cohort Study of Patient Pain, Anxiety, and Satisfaction.

BACKGROUND: Staged interpolation flaps (SIFs) have historically been performed under general anesthesia by specialties outside of dermatologic surgery. However, SIFs performed under local anesthesia by dermatologic surgeons have shown lower or equal complication rates. OBJECTIVE: To date, no studies have evaluated pain, anxiety, satisfaction, and use of perioperative analgesics in patients undergoing SIFs in an outpatient setting under local anesthesia. METHODS/MATERIALS: This is a prospective cohort study of 39 patients who received Mohs micrographic surgery and subsequent SIF repair in an outpatient setting under local anesthesia. Pain, anxiety, and satisfaction scores were recorded using 100-point validated visual analog scales. Perioperative analgesic use was quantified. RESULTS: The defect size was ≥4 cm2 in 72% of patients; 41% had full-thickness (skin/cartilage/mucosa) defects. All pain and anxiety measures were minimal to mild. Pain scores ranged from highest (mean = 39 ± 4.1) on postoperative Day (POD) 1 to lowest (mean = 12.3 ± 2.0) on POD 7. Anxiety scores ranged from highest (mean = 42 ± 4.5) on POD 1 to lowest (mean = 18.5 ± 3.7) on POD 7. Perioperative patient satisfaction was high (mean = 95 ± 1.7). Postoperative narcotic analgesics were prescribed in 15% of patients. CONCLUSION: Staged interpolation flaps performed under local anesthesia in the outpatient setting are well tolerated with low pain and anxiety, high patient satisfaction, and minimal analgesic use.

Reconstruction of Distal Nasal Defects Using Free Cartilage Batten Grafting With Secondary Intention Healing: A Retrospective Case Series of 129 Patients.

BACKGROUND: Surgical defects of the distal nose can pose significant reconstructive challenges. Free cartilage batten graft (FCBG) with secondary intention healing is an underreported yet effective repair option with cosmetically and functionally satisfying outcomes. OBJECTIVE: To share the authors' experience using FCBG with secondary intention healing on multiple nasal subunits, including a detailed evaluation of wound/graft characteristics and design modifications to optimize success with this single-stage approach. METHODS: A retrospective study of 129 patients who underwent FCBG with secondary intention healing after Mohs surgery from 2011 to 2018, using statistical analysis of numerous outcome measures graded independently by 2 fellowship-trained Mohs surgeons. RESULTS: Overall, healed wounds were graded aesthetically as follows: excellent (24%), very good (31%), good (31%), or poor (14%). Excellent/very good outcomes were seen for superficial (p < .001), small-to-medium sized wounds (p < .0001) repaired with cartilage that closely approximated the defect size (p < .05). Consistently optimal outcomes were seen in the 19 repairs involving the alar lobule (mid-ala) alone, graded excellent (47%), very good (32%), and good (21%). A majority of patients (86%) experienced mild to no alar retraction. Although 67% of all patients had some skin surface contour irregularity, only 8% of patients sought dermabrasion. Neither hematoma, infection, ear deformity, chondritis, nor graft desiccation were reported. CONCLUSION: A modified approach to FCBG with secondary intention healing provides a reliable, minimalistic, low-risk reconstructive option for mid-alar defects.

Keratosis pilaris rubra with mucin deposition.

Keratosis pilaris (KP) is a benign cutaneous disorder characterized by folliculocentric hyperkeratotic papules most often occurring on the proximal extremities. Erythema is usually limited to perifollicular skin, but when keratosis pilaris presents on a background of confluent erythema, the term keratosis pilaris rubra (KPR) is used. The histological findings associated with KP have not been well described in the literature. Herein, we present a case of a 14-year-old male with a 7-year history of erythema and follicular-based papules over his bilateral cheeks, consistent with KPR. Histological examination revealed abundant mucin, keratotic follicular plugging, and periadnexal lymphocytosis. Our novel finding of abundant dermal mucin expands the histopathologic description of KPR.

Diffuse cutaneous mastocytosis: Case report and literature review.

A 6-month-old boy was referred to our burn unit with a recurrent bullous dermatitis, fever, and emesis, originally diagnosed as staphylococcal scalded skin syndrome (SSSS) at an outside hospital. Infectious workup was negative and shave biopsy revealed a dense, diffuse dermal infiltrate of mast cells, consistent with diffuse cutaneous bullous mastocytosis-a rare variant of cutaneous mastocytosis. Treatment included a prolonged course of corticosteroids and antihistamines. Recognition of this rare form of mastocytosis is important, as it can be easily mistaken for other pediatric bullous diseases and is associated with life-threatening complications including vasodilation, anaphylactic shock, gastrointestinal bleeding, and death.

Amphotericin B releasing nanoparticle topical treatment of Candida spp. in the setting of a burn wound.

Candida spp. infection in the context of burn wounds leads to invasive disease with a 14-70% mortality rate. Unfortunately, current administrations of AmB, an important therapeutic demonstrating minimal resistance, are only available via potentially cytotoxic IV infusions. In order to circumvent these sequelae, we investigated the efficacy of nanoparticle encapsulated AmB (AmB-np) as a topical therapeutic against Candida spp. (drug release equilibrated solubilized AmB [AmB-sol] included as control). Clinical strains demonstrated equal or enhanced killing efficacy with 72.4-91.1% growth reduction by 4 hours. AmB-nps resulted in statistically significant reduction of fungal biofilm metabolic activity ranging from 80% to 95% viability reduction (P<0.001). Using a murine full-thickness burn model, AmB-np exhibited a quicker efficiency in fungal clearance versus AmB-sol by day three, although wound healing rates were similar. These data support the concept that AmB-np can function as a topical antifungal in the setting of a burn wound. FROM THE CLINICAL EDITOR: The control of fungal infections with Candida species remains a challenge in the context of burn wounds. A nanoencapsulated topical amphotericin-B compound was studied in a murine model of full thickness burn injury, showing remarkable efficacy in controlling Candida infection. This may become a viable alternative to the potentially toxic intravenous formulations.

Myocosis fungoides--an update on a non-mycotic disease.

Mycosis fungoides was first described in 1806 by the French physician Jean Louis Alibert in a patient whose skin lesions developed into mushroom-like tumors. Though it is not an infectious disease, it was termed mycosis fungoides (MF) due to its fungating appearance. In 1870, Bazin further described MF, proposing the three classical stages of the cutaneous disease: patch, plaque, and tumor. The term cutaneous T-cell lymphoma (CTCL) was first utilized in 1975 by Lutzner et al to describe a group of malignant infiltrative disorders of the skin including MF and Sézary syndrome. CTCLs comprise a spectrum of extranodal non-Hodgkin's lymphomas that are characterized by primary cutaneous involvement of a dominant clonal T-cell. As molecular biology and immunohistochemistry techniques have become more developed, CTCL has become understood to be a heterogeneous assembly of disorders that vary with regards to clinical course, histopathology, therapeutic considerations, and prognosis. MF, a low-grade lymphoproliferative disorder, is the most common type of CTCL, comprising 54% of CTCLs. It is a rare, extranodal, non-Hodgkin's lymphoma and is an epidermotropic neoplasm composed of CD4+ (helper) lymphocytes Sézary syndrome is a related leukemic subtype of CTCL that presents with diffuse skin involvement as well as circulating tumor cells in the peripheral blood.

Pityriasis rosea-like drug reaction to asenapine.

Pityriasis rosea (PR) is a relatively common, benign skin disease of unknown etiology. In rare cases, medications can induce a morphologically similar eruption. We present a case of a PR-like drug eruption caused by the atypical antipsychotic asenapine. The clinical presentation consisted of a rapidly progressive, disseminated, and severely pruritic dermatitis comprised of ovoid, scaly, pink-violaceous plaques. The initial histopathologic specimen was consistent with PR, but upon re-sampling a week later, the findings favored a drug eruption. PR-like drug eruptions, though rare, can occur in response to a wide variety of medications. Because the findings may be only subtly different than those of typical PR, careful clinical and histopathological correlation must be sought. To our knowledge, this is the first reported case of a PR-like drug eruption to asenapine.

Evaluation of the antibiotic properties of glutathione.

Skin and soft tissue infections (SSTIs) are growing in prevalence in both the outpatient and inpatient settings and are some of the most common diseases seen by dermatologists, who are often the first point of care for these patients. Microbial resistance to antibiotics continues to rise as more virulent strains evolve, and strains predominantly found in the hospital setting are now being seen in the community. Therefore, innovative approaches to combat this trend are needed. Glutathione (GSH) is a well-described and established antioxidant. It participates in detoxification of xenobiotics, regulation of cellular growth, modulation of immune response, and maintenance of the thiol status of proteins and cellular cysteine levels. GSH is also known to have a regulatory effect on immune cells and even inherent antibacterial properties have been reported. To this end, the value of GSH as an antibiotic was evaluated by growing methicillin resistant S. aureus, E. coli, K. pneumoniae and P. aeruginosa strains isolated from human skin and soft tissue infection in the presence of GSH. At a physiologic concentration of 10 mM, GSH had no effect on bacterial growth. At concentrations above 50 mM, which created acidic conditions (pH < 4), bacterial growth was completely inhibited. When adjusted to physiologic pH, GSH exhibited a bacteriostatic effect in a concentration-dependent manner. Additionally, the cytotoxicity of GSH was evaluated in a murine cell line. GSH was relatively non-toxic to murine macrophages, even at the highest concentration tested (160 mM). These results suggest the potential utility of GSH for the prevention and/or as adjunctive treatment of infection, most significantly in disease states associated with GSH deficiency.

Nitrosoglutathione generating nitric oxide nanoparticles as an improved strategy for combating Pseudomonas aeruginosa-infected wounds.

Pseudomonas aeruginosa is a community-acquired, nosocomial pathogen that is an important cause of human morbidity and mortality; it is intrinsically resistant to several antibiotics and is capable of developing resistance to newly developed drugs via a variety of mechanisms. P aeruginosa's ubiquity and multidrug resistance (MDR) warrants the development of innovative methods that overcome its ability to develop resistance. We have previously described a nitric oxide-releasing nanoparticle (NO-np) platform that effectively kills gram-positive and gram-negative organisms in vitro and accelerates clinical recovery in vivo in murine wound and abscess infection models. We have also demonstrated that when glutathione (GSH) is added to NO-np, the nitroso intermediate S-nitrosoglutathione (GSNO) is formed, which has greater activity against P aeruginosa and other gram-negative organisms compared with NO-np alone. In the current study, we evaluate the potential of NO-np to generate GSNO both in vitro and in vivo in a murine excisional wound model infected with an MDR clinical isolate of P aeruginosa. Whereas NO-np alone inhibited P aeruginosa growth in vitro for up to 8 hours, NO-np+GSH completely inhibited P aeruginosa growth for 24 hours. Percent survival in the NO-np+GSH-treated isolates was significantly lower than in the NO-np (36.1% vs 8.3%; P=.004). In addition, NO-np+GSH accelerated wound closure in P aeruginosa-infected wounds, and NO-np+GSH-treated wounds had significantly lower bacterial burden when compared to NO-np-treated wounds (P<.001). We conclude that GSNO is easily generated from our NO-np platform and has the potential to be used as an antimicrobial agent against MDR organisms such as P aeruginosa.

Tumescent contravenom: murine model for prehospital treatment of Naja naja neurotoxic snake envenomation.

BACKGROUND: Snake envenomation is a neglected global health problem. There is a need for a prehospital treatment of neurotoxic snakebite that prolongs survival and allows time for a victim to reach a hospital for antivenom therapy. Tumescent epinephrine consists of a large volume of dilute epinephrine (2 mg/l) injected subcutaneously. It functions as "contravenom" by causing capillary vasoconstriction and delaying venom absorption. METHODS: A murine model of neurotoxic envenomation using lidocaine as a surrogate for neurotoxic snake venom was first developed in a pilot study. A lethal dose of lidocaine was injected subcutaneously into control and treatment groups. Mice in the treatment group were then treated with a tumescent infiltration of dilute epinephrine in saline, while control mice either received no treatment or tumescent infiltration with saline alone. The experiment was repeated using lethal doses of neurotoxic Naja naja cobra venom. The main end-points were survival rate and survival time. RESULTS: None of the control mice survived a lethal (LD100 ) dosage of subcutaneous lidocaine. Mice given an LD100 of subcutaneous lidocaine and treated immediately with tumescent epinephrine had 80% survival. Following LD50 doses of Naja naja venom, 50% of control mice survived, while 94% survived when treated immediately with tumescent epinephrine (P < 0.01). All animals died following LD100 doses of Naja naja venom, but survival was significantly prolonged (P < 0.0001) by immediate tumescent epinephrine. CONCLUSIONS: Tumescent epinephrine, when given immediately after toxin injection, improves survival rates in mice following neurotoxic doses of lidocaine or Naja naja cobra venom.

Nanoparticle-Encapsulated Doxorubicin Demonstrates Superior Tumor Cell Kill in Triple Negative Breast Cancer Subtypes Intrinsically Resistant to Doxorubicin.

The effect of size and release kinetics of doxorubicin-nanoparticles on anti-tumor efficacy was evaluated in a panel of human cancer cell lines, including triple-negative breast cancer (TNBC) cells that frequently demonstrate resistance to doxorubicin. Different nano-formulations of sol-gel-based Doxorubicin containing nanoparticles were synthesized. Increased cell kill in chemoreffactory triple-negative breast cancer cells was associated with the smallest size of nanoparticles and the slowest release of Dox. Modeling of dose-response parameters in Dox-sensitive versus Dox-resistant lines demonstrated increased EMax and area under the curve in Dox-resistant mesenchymal TNBC cells, implying potentially favorable activity in this molecular subtype of breast cancer. Mesenchymal TNBC cells demonstrated a high rate of fluorescent bead uptake suggestive of increased endocytosis, which may partially account for the enhanced efficacy of Dox-np in this subtype. Thus, manipulation of size and release kinetics of this nanoparticle platform is associated with enhanced dose-response metrics and tumor cell kill in therapeutically recalcitrant TNBC cell models. This platform is easily customizable and warrants further exploration.

Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing.

Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than twofold increase in the rate of cell movement, in part due to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds.

Novel insights of the gastric gland organization revealed by chief cell specific expression of moesin.

ERM (ezrin, radixin, and moesin) proteins play critical roles in epithelial and endothelial cell polarity, among other functions. In gastric glands, ezrin is mainly expressed in acid-secreting parietal cells, but not in mucous neck cells or zymogenic chief cells. In looking for other ERM proteins, moesin was found lining the lumen of much of the gastric gland, but it was not expressed in parietal cells. No significant radixin expression was detected in the gastric glands. Moesin showed an increased gradient of expression from the neck to the base of the glands. In addition, the staining pattern of moesin revealed a branched morphology for the gastric lumen. This pattern of short branches extending from the glandular lumen was confirmed by using antibody against zonula occludens-1 (ZO-1) to stain tight junctions. With a mucous neck cell probe (lectin GSII, from Griffonia simplicifolia) and a chief cell marker (pepsinogen C), immunohistochemistry revealed that the mucous neck cells at the top of the glands do not express moesin, but, progressing toward the base, mucous cells showing decreased GSII staining had low or moderate level of moesin expression. The level of moesin expression continued to increase toward the base of the glands and reached a plateau in the base where chief cells and parietal cells abound. The level of pepsinogen expression also increased toward the base. Pepsinogen C was located on cytoplasmic granules and/or more generally distributed in chief cells, whereas moesin was exclusively expressed on the apical membrane. This is a clear demonstration of distinctive cellular expression of two ERM family members in the same tissue. The results provide the first evidence that moesin is involved in the cell biology of chief cells. Novel insights on gastric gland morphology revealed by the moesin and ZO-1 staining provide the basis for a model of cell maturation and migration within the gland.