Histopathology of persistent long COVID toe: A case report.

During the 2020 coronavirus (SARS-CoV-2) pandemic, several cutaneous lesions were identified, including pseudo-chilblain, vesicular, urticarial, maculopapular, and livedo/necrosis. A 59-year-old obese man with probable COVID-19 developed painful cyanosis with histopathologic capillary thrombosis of toes, and the cyanosis persisted for nearly 22 months. Shortly after initial exposure to family members with documented SARS-CoV-2, he developed upper respiratory symptoms, yet his anti-SARS-CoV-2 antibody and nasal swab RT-PCR tests were repeatedly negative. Two family members were hospitalized and one of them succumbed with documented SARS-CoV-2 pneumonia within 10 days of exposure. Biopsy specimen of the distal toe 16 weeks after initial exposure showed papillary dermal capillary thrombosis with endothelial swelling, telangiectasia, and peri-eccrine lymphocytic infiltrates resembling pernio. Overall, this is the first case of biopsy specimen of "long COVID toe" following presumed SARS-CoV-2 exposure, with a demonstration of thrombotic vasculopathy, toe cyanosis, and pernio-like pathology.

The Maximum-Tolerated Dose and Pharmacokinetics of a Novel Chemically Modified Curcumin in Rats.

PURPOSE: CMC 2.24, a chemically modified curcumin, was developed as a novel, pleiotropic MMP-inhibitor to treat various inflammatory/collagenolytic diseases including periodontitis. To date, this compound has shown efficacy in vitro, in cell culture, and in vivo (oral administration) in mice, rats and dogs. In preparation for possible Phase I human clinical trials, the current study describes the maximum-tolerated-dose (MTD), pharmacokinetics (PK), and toxicology of CMC 2.24 in the rat model. METHODS: For the MTD study, 30 Sprague-Dawley rats were randomly distributed into 5 groups (3M/3F per group): Placebo (vehicle; carboxymethylcellulose) and CMC 2.24 at various doses (50, 100, 500, 1000 mg/kg/day), were administered once daily by oral gavage for 5 days. For the PK study, 24 rats were administered either Placebo or CMC 2.24 (100mg/kg/day) once daily for 28 days or only once (500 or 1000 mg/kg). Analysis of this test compound was done using LC/MS/MS for PK evaluation on blood samples drawn from rats at multiple time points. The animals were sacrificed after 5 or 28 days of treatment, and blood chemistry and serology were analyzed. Major organs (heart, lung, liver, kidney, spleen, intestine, brain) were histologically examined at necropsy. RESULTS: Orally administered, CMC 2.24 did not produce significant changes in body weight, food consumption or adverse events in the MTD and toxicology studies. Moreover, no obvious pathologic changes were observed based on histology, hematology, serum biochemistry, or necropsy compared to placebo-treated controls. The PK study demonstrated a peak-blood concentration (Cmax) at 45 mins after oral administration of 2.24 and a serum half-life of 10 hours. CONCLUSION: In conclusion, CMC 2.24, orally administered to rats once a day, appears to be safe and effective at a wide range of doses, consistent with efficacy previously demonstrated in studies on animal models of various collagenolytic diseases, such as periodontitis, diabetes and cancer.

Comparison of comparable scald and contact burns in a porcine model: A preliminary report.

Whether the depth and healing of scalds and contact burns are similar is controversial. Due to water's greater heat capacity, we hypothesized that when exposed to similar temperatures and durations of exposure, burns caused by hot water would be deeper than those caused by contact with hot metal. Forty standardized burns were created in two anesthetized female domestic pigs using a brass bar or circulating heated water. In one pig, the temperature was kept constant (95°C) while the duration of exposure varied (5, 10, 15 seconds) In the second pig, the exposure time was kept constant (10 seconds) while the temperature of exposure varied (70°C, 80°C, 98°C). Periodic punch biopsies were taken to determine burn depth immediately after injury, percentage burns reepithelialized within 21 days, and depth of scar at 28 days. The analysis was performed using analysis of variance. When the temperature was held constant, duration of exposure (5, 10, and 15 seconds) was associated with scar depth (2.1 vs 3.8 vs 5.0 mm, respectively, P = 0.001) but not with burn depth (2.0 vs 2.2 vs 2.3 mm, respectively, P = 0.10). When exposure duration was held constant, temperature (70°C, 80°C, 98°C) was associated with scar depth (0.6 vs 1.7 vs 3.6, P < 0.001) but not with burn depth (1.2 vs 1.5 vs 1.7 mm, respectively, P = 0.21). Burn depths were greater for scald than contact burns although not significantly greater. After controlling for temperature, the difference in scar depth between scalds and contact burns was statistically significant (marginal means 3.0 for contact burns, 4.3 for scalds, P = 0.008). We conclude that burns created in swine with circulating hot water result in deeper scars than those created by contact with a brass bar when controlling for temperature and duration of exposure.

Effect of tadalafil on reduction of necrosis in the ischemic zone in a rat comb burn model.

OBJECTIVES: A major goal of burn management is to reduce the progression of necrosis in the zone of ischemia surrounding the central zone of necrosis. A rat comb burn model is often used to assess the progression of necrosis in the zone of ischemia. We compared various combinations of naproxen [NPX], N-acetyl cysteine [NAC], and tadalafil [TD] (a phosphodiesterase-5 inhibitor used as a vasodilator to treat erectile dysfunction) in a rat comb burn model to determine their effects on injury progression. METHODS: We created two comb burns on the backs of 40 anesthetized Sprague-Dawley rats using a brass comb with four rectangular prongs preheated in boiling water and applied for 30s, resulting in four rectangular 10×20mm full-thickness burns separated by three 5×20mm unburned interspaces, representing the ischemic zones. We randomized five animals each to daily oral gavage with TD (1mg/kg), NPX (10mg/kg), NAC (500mg/kg), NAC+NPX, TD+NPX, TD+NAC, TD+NPX+NAC, or normal saline [NS]. Wounds were observed daily for gross evidence of necrosis in the unburned interspaces and full-thickness biopsies from the interspaces were evaluated with Hematoxylin & Eosin seven days after injury for histological evidence of necrosis. RESULTS: The percentages of interspaces with histological evidence of necrosis at day seven were TD-40%, NPX-93%, NAC-97%, NS-87%, TD+NPX-50%, TD+NAC-40%, TD+NPX+NAC-33%, and NPX+NAC-60% (P<0.001). Repeated measures ANOVA demonstrated reduced gross percentage of interspace area undergoing necrosis in all groups that included TD, compared with all groups not including TD (P<0.001). There were no differences among the various treatments within the groups that did or did not include TD. CONCLUSIONS: Daily oral therapy with tadalafil reduces necrosis in the unburned interspaces compared with naproxen, NAC, or their combination in a rat comb burn model. Addition of naproxen or NAC to tadalafil does not further reduce injury progression.

Blood vessel occlusion with erythrocyte aggregates causes burn injury progression-microvasculature dilation as a possible therapy.

Burns are dynamic injuries characterized by progressive tissue death and continuous severe pain over the course of several days. The extent of burn injury progression determines the ultimate patient outcome. Initial burns result in a central zone of necrosis surrounded by a potentially viable zone of ischemia. Several mechanisms have been proposed to explain injury progression, including oxidant and cytokine stress resulting from either ischemia/reperfusion and/or inflammation, but no proven therapy has emerged. To address the unmet need to limit burn injury progression, the root cause of this process must be delineated. For this reason, we have recently focused on post-burn blood vessel occlusion, currently ascribed to microthrombi. We have found that blood vessel occlusion is initially, mainly and persistently caused by erythrocyte aggregation. Although thermal-induced cell necrosis is the immediate cause of cell death, apoptotic cells from persistent ischemia/anoxia, admixed with inflammatory cells, form a band between viable and nonviable tissue 24 hours later. The delayed cell death by apoptosis appears to be the main attractant for inflammatory cells. Finally, we posit that fibrinogen elevation arising from inflammation provides stimulus for additional erythrocyte aggregation, further extending blood vessel occlusion. In our view this persistent occlusion with resultant prolonged tissue ischemia/anoxia, not ischemia/reperfusion, is the root cause of burn injury progression concomitant with associated severe and persistent pain. Epiviosamines, a new class of peptides, appear to selectively dilate microvasculature, and may provide therapy for burn injury progression.

The effects of topical nitric oxide on healing of partial thickness porcine burns.

BACKGROUND: Nitric oxide is a wound mediator that promotes wound healing. We hypothesized that topical application of nitric oxide would speed reepithelialization, enhance angiogenesis, and reduce scar thickness in a partial thickness porcine burn model. METHODS: While under general anesthesia, 20 partial thickness burns were created on the backs of four female Yorkshire swine using a 2.5cm×2.5cm×7.5cm, 150-g aluminum bar, preheated to 80°C and applied for 20s. The necrotic epidermis was removed and the burns were randomized to low, medium, and high concentrations of a novel nitric-oxide (NO) releasing drug or its ointment vehicle applied 3 times weekly for 28 days. Full thickness punch biopsies were performed at 8, 11, 14 and 28 days after injury to determine percentage wound reepithelialization and scar thickness using H&E staining and blood vessel density using CD31 staining. RESULTS: At day 11, the percentages (SD) wound reepithelialization were: control, 26.3 (34.6); low NO, 23.9 (36.9); medium NO, 43.3 (42.9); and high NO, 59.9 (43.6); ANOVA, P=0.02. The number of CD31 stained blood vessels at days 8 and 11 were greater in wounds treated with high dose NO vs. controls (48.1 vs. 22.9 [P<0.001] and 44.0 vs. 33.5 [P=0.05] per 1mm2 respectively). Scar thicknesses (SD) in mm at day 28 by treatment allocation were: control, 4.8 (1.2); low NO, 4.7 (1.2); medium NO, 4.3 (1.2); and high NO, 4.1 (1.0); P=0.22. CONCLUSIONS: Treatment of partial thickness porcine burns with high concentrations of topical NO resulted in earlier reepithelization and increased angiogenesis but not reduced scar thickness compared with its control vehicle in a partial thickness porcine burn model.

Enhanced Mortality to Metastatic Bladder Cancer Cell Line MB49 in Vasoactive Intestinal Peptide Gene Knockout Mice.

To identify if the absence of the vasoactive intestinal peptide (VIP) gene enhances susceptibility to death from metastatic bladder cancer, two strains of mice were injected with MB49 murine bladder cancer cells. The growth and spread of the cancer was measured over a period of 4 weeks in C57BL/6 mice and 5 weeks in VIP knockout (KO) mice. A Kaplan-Meier plot was constructed to compare control C57BL/6 mice and C57BL/6 mice with MB49 vs. VIP KO controls and VIP KO mice with MB49. The wild-type (WT) strain (C57BL/6) contained the VIP gene, while the other strain, VIP knockout backcrossed to C57BL/6 (VIP KO) did not and was thus unable to endogenously produce VIP. VIP KO mice had increased mortality compared to C57BL/6 mice at 4 weeks. The number of ulcers between both groups was not statistically significant. In vitro studies indicated that the presence VIP in high doses reduced MB49 cell growth, as well as macrophage inhibitory factor (MIF), a growth factor in bladder cancer cells. These findings support the concept that VIP may attenuate susceptibility to death from bladder cancer, and that it exerts its effect via downregulation of MIF.

Early versus Delayed Excision and Grafting of Full-Thickness Burns in a Porcine Model: A Randomized Study.

BACKGROUND: The standard of care for full-thickness burns is tangential excision followed by skin autografting; however, the timing of excision and grafting is subject to debate. The authors compared early (2 days) versus delayed (14 days) excision and grafting in a porcine full-thickness burn model. METHODS: Full-thickness burns (n = 12) were created on the backs of two anesthetized pigs and assigned randomly to no excision, tangential excision followed by skin autografting 2 days after injury, or tangential excision followed by skin autografting 14 days after injury. Digital images and full-thickness biopsy specimens were taken at 16, 21, 28, and 42 days after injury to determine percentage reepithelialization and scar depth. RESULTS: At day 16, all burns that were excised early were completely reepithelialized, whereas only eight of 11 nonexcised burns (72.7 percent) were reepithelialized (p = 0.02). By day 21, all burns were completely reepithelialized. Scar thickness was greatest at 42 days in nonexcised burns (7.5 ± 2.1 mm); scars were thinner after early excision than after late excision (2.2 ± 1.8 mm versus 4.0 ± 1.1 mm; p < 0.001, analysis of variance). Wounds treated with early or late tangential excision followed by skin autografting were flat and minimally contracted, whereas all nonexcised burns were red, contracted, and slightly raised. Scar contraction at 28 and 42 days was greatest in nonexcised control wounds compared with early and late excised wounds. CONCLUSIONS: Both early and late excision followed by autografting reduce scarring in a full-thickness porcine burn model. However, early excision (2 days after injury) reduces scar thickness to a greater extent than later (after 14 days) excision.

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay.

BACKGROUND: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. METHODS: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (10(9) pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. RESULTS: AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm(2), P < 0.01 and 12.4 ± 1.2 cm(2), P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm(2)). CONCLUSIONS: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not.

Laser-assisted indocyanine green dye angiography accurately predicts the split-thickness graft timing of integra artificial dermis.

BACKGROUND: The use of an artificial dermal substitute such as Integra-a bilaminate combination of thin silicone and cross-linked bovine tendon collagen and chondroitin-6-sulfate-has become a popular method to address large surface area wounds or smaller, complex wounds devoid of a vascular bed. The incorporation of Integra depends on a vascular wound bed or periphery and can take 4 weeks or longer to occur. If the Integra has not fully incorporated at the time of placement of the split-thickness graft, complete graft loss may result. The availability of a minimally invasive method to assess the incorporation of Integra would be of great value. METHODS: Two 5 × 10-cm paraspinal full-thickness wounds were created on 3 female swine. Wounds were randomly assigned full-thickness skin graft or Integra (Plainsboro, NJ) treatment. Both types of grafts were placed after the application of fibrin glue (Tisseel, Deerfield, Ill) to the wound bed. Laser Doppler imaging (LDI) (Moor), indocyanine green dye (ICG) angiography (LifeCell SPY), and clinical scoring were performed weekly for a period of 8 weeks after grafting. At 4 weeks, the silicone layer of the Integra was removed, and a culture of autologous keratinocytes was applied. A 4-mm punch biopsy sample of each graft was taken 1, 2, 4, 6, 7, and 8 weeks postoperatively for histologic analysis. RESULTS: Both ICG angiography and LDI perfusion measurements noted an increase in perfusion at the Integra graft site that peaked 3 weeks after grafting, corresponding with the start of neovascularization and the optimal time for the application of a split-thickness skin graft. indocyanine green dye angiography measurements exhibit greater reproducibility between animals at late time points as compared with LDI. This decrease in LDI precision is directly related to increases in scar tissue thickness of greater than 5 mm as determined via histologic analysis and corresponds with the accepted maximum penetration depth of the LDI laser. CONCLUSIONS: Indocyanine green dye angiography may provide valuable information as to graft integrity and split-thickness skin graft timing at late time points. Range of LDI seems to be insufficient for split-thickness graft timing or late time point accuracy. Future exploration of ICG angiography potential will involve tracking Integra graft delay in porcine models.

Fibronectin peptides that bind PDGF-BB enhance survival of cells and tissue under stress.

Stressors after injury from a multitude of factors can lead to cell death. We have identified four fibronectin (FN) peptides: two from the first FN type III repeat (FNIII1), one from the 13th FN type III repeat (FNIII13), and one from FN variable region (IIICS), which when tethered to a surface acted as platelet-derived growth factor-BB (PDGF-BB) enhancers to promote cell survival. One of the FNIII1 peptides and its smallest (14-mer) bioactive form (P12) were also active in solution. Specifically, P12 bound PDGF-BB (KD=200 nM), enhanced adult human dermal fibroblast (AHDF) survival under serum starvation, oxidative or endoplasmic reticulum stressors, and limited burn-injury progression in a rat hot comb model. Furthermore, P12 inhibited endoplasmic reticulum stress-induced c-Jun N-terminal kinase (JNK) activation. Although many growth factors have been found to bind FN directly or indirectly, here we identify peptide sequences of growth factor-binding sites in FN. The finding of these peptides further delineated how the extracellular matrix protein FN can support cell survival. As the peptide P12 is active in either soluble form or tethered to a substrate, it will have multifactorial uses as a bioactive peptide by itself or in tissue engineering.

Melanoma masquerading as xanthogranuloma: a diagnostic pitfall.

Melanoma can present with protean combinations and permutations of histologic features mimicking a plethora of nonmelanocytic benign and malignant proliferations. Anecdotal cases of melanoma closely simulating fibrohistiocytic proliferations have been reported. At times, the reliable differentiation between melanoma and histiocytic proliferations could be vexing histopathologically. We report an unusual presentation of melanoma in an 87-year-old man strikingly resembling xanthogranuloma both clinically and histopathologically. Histologic sections revealed a diffuse proliferation of pleomorphic cells some with foamy cytoplasm and occasional Touton-like giant cells in the dermis accompanied by inflammatory cells. Rare single-cell pagetoid scatter was evident within the epidermis. The infiltrate had patchy staining on CD163, interpreted as part of the inflammatory component but the atypical cells stained heavily with Melan A and tyrosinase confirming the diagnosis of malignant melanoma. Our case demonstrates yet another face of malignant melanoma and the critical but judicious use of immunohistochemistry in reliably distinguishing between melanoma and histiocytic tumors.

Lack of agreement between gross visual and histological assessment of burn reepithelialization in a porcine burn model.

One of the most important and earliest measures of burn healing is wound reepithelialization. Reepithelialization is a vital determinant of wound infection and scarring. Reepithelialization is generally based on gross visual assessment; however, histological assessment remains the criterion standard. We hypothesized that there would be poor agreement (r < .4) between gross visual and histological assessments of burn reepithelialization in a porcine model. The study design was prospective observational using three anesthetized female pigs (20-25 kg). Forty-eight 2.5- × 2.5-cm burns were created on the flanks of pig's using an aluminum bar (150 g) preheated to 80°C for 20 seconds. Burns were treated with an occlusive or antimicrobial dressing and photographed at day 10 for determination of gross percentage reepithelialization in a 1-cm diameter circle in the center of the burn by two experienced clinicians masked to each other's measurements. A 10-mm full-thickness punch biopsy was taken from the center of the burns and evaluated by a board-certified dermatopathologist masked to clinical assessments. One clinician and the dermatopathologist repeated the assessments 1 month apart. The outcome was percentage wound reepithelialization at 10 days. The criterion standard was the histological assessment. Intraobserver and interobserver agreements were calculated with Pearson's correlation coefficients. A coefficient less than .4 was considered poor. Sixteen burns were created on each of three animals. Six wounds were excluded because of the presence of a thick eschar covering the burn, making the gross determination of reepithelialization impossible. Intraobserver agreement for histological reepithelialization was 0.96 (P < .001). Intraobserver agreement for gross visual assessment of reepithelialization was 0.75 (P < .001). Interobserver agreement for gross visual assessment of reepithelialization was 0.60 (P < .001). The agreement between gross visual and histological assessment of burn reepithelialization was -0.25. Although there was a good interobserver agreement for gross visual assessments, there was a poor agreement between gross visual and histological assessments of burn reepithelialization. Care should be used when determining burn reepithelialization based on gross visual assessments alone.

Melanoma screening with serial whole body photographic change detection using Melanoscan technology.

The use of an automated, whole-body, diffusely lit digital imaging enclosure to produce serial images, which were then compared, using an astrophysics image display method, enabled a private practice dermatologist to detect melanoma at significantly thinner Breslow depths compared to all other clinical detection paradigms examined in this study. The patients were triaged to scanning using a melanoma risk survey system. The system employed a 24 camera semicircular imaging wall, with front and back views. 10,000 whole body photographic scans were obtained. Privacy was maintained with 128-bit image encryption and off-line storage. Image to image comparison of whole body digital photography was combined with a whole body skin exam in order to sensitize a clinical dermatologist to skin changes in individuals at risk for melanoma. Mean depths (Breslow scores) were compiled from six distinct melanoma biopsy cohorts segregated and based on different clinical screening paradigms. The Breslow depth of invasive lesions of the serial screening cohort was significantly less (by at least 0.050 mm) compared to three other clinical screening groups (patient self-detection 0.55 mm, p=0.007; referred by outside non-dermatologist physician 0.73 mm, p=0.03; and serial dermatologic evaluation 0.23 mm, p=0.03) as well as two pathology laboratory cohorts (community hospital laboratory 1.45 mm, p=0.003; dermatopathology laboratory 0.18, p=0.0003). This approach provides a quick and effective method for detection of early melanomas with a significant reduction in the skin area required for lesion examination.

Apoptosis and necrosis in the ischemic zone adjacent to third degree burns.

OBJECTIVES: Burns are characterized by a central zone of necrosis surrounded by a zone of potentially reversible ischemia. The authors explored the contribution of necrosis and apoptosis to cell death in the zone of ischemia. METHODS: A previously established rat contact thermal injury model that utilizes a brass comb to produce four distinctive burns sites separated by three "interspaces" of unburned skin was used. The interspaces represent the zone of stasis or ischemia while the burn sites represent the zone of coagulation. With this model, most unburned interspaces progress to necrosis over 2 to 3 days. Full-thickness 3-mm biopsies were obtained from the interspaces, burns, and normal skin controls at 30 minutes, 24 hours, and 48 hours after injury. Slides were stained with hematoxylin and eosin as well as activated cleaved caspase-3 (CC3a) for evidence of apoptosis and high-mobility group box 1 (HMGB1) for evidence of necrosis. RESULTS: Necrosis was not seen at 30 minutes, but was found in a large number of cells within the epidermis, sebaceous glands, and follicles at 24 and 48 hours. Faint nuclear CC3a staining indicative of apoptosis was present in a minority of cells within the epidermis, dermal fibroblasts, dermal follicles, and dermal sebaceous glands at 30 minutes and to a lesser degree at 24 and 48 hours. CONCLUSIONS: Both early apoptosis and delayed necrosis are present in the zone of ischemia, contributing to injury progression. Necrosis appears to play a larger role than apoptosis in injury progression in the comb burn model.

Porcine wound healing in full-thickness skin defects using Integra™ with and without fibrin glue with keratinocytes.

BACKGROUND: An artificial dermal matrix such as Integra (Integra Life Sciences Corporation, USA) provides a wound bed template for vascular and fibrocyte ingrowth as well as collagen remodelling. Dermal repair leads to epidermal and basement membrane regeneration. Burn wounds in particular have been shown to benefit from Integra by enhanced wound healing. OBJECTIVE: To evaluate the effect of fibrin glue to modify the integration of Integra in large excised cutaneous wounds. It was hypothesized that applying fibrin glue on a wound bed would reduce the time needed for matrix vascularization and incorporation of Integra and take of the cultured keratinocytes. METHODS: Four separate full-thickness wounds were created on the dorsum of two swine. Wound beds were randomly assigned to either application of fibrin glue or no application of fibrin glue before application of Integra. Full-thickness biopsies were performed at days 7, 14, 21, 29 and 35. On day 21, keratinocytes were applied either as sheets or aerosolized fibrin glue suspension. RESULTS: Histological analysis revealed a wave of inflammatory cells and early granulation tissue ingrowth into the Integra from the fascia below on day 7. Only this initial phase was augmented by application of fibrin glue to the wound bed. By day 14, most and by day 21, all of the Integra thickness was incorporated. Accelerated dermal repair proceeded from the base with new collagen deposition in Integra spaces. There was no evidence of keratinocyte engraftment, although re-epithelialization occurred at wound edges extending onto the incorporated Integra. CONCLUSIONS: It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension.

Ex vivo dermoscopy of melanocytic tumors: time for dermatopathologists to learn dermoscopy.

BACKGROUND: We have identified cases of skin cancer with discordances between clinical, dermoscopic, and histopathologic findings that were likely due to sampling errors in the pathology laboratory. This has prompted us to explore the use of ex vivo dermoscopy as an ancillary method of gross pathology, which may serve to guide tissue sectioning. Noncontact polarized dermoscopy was applied to pigmented lesions before excision and at least 6 hours after specimen fixation in formalin. OBSERVATIONS: The orientation of the lesion, overall dermoscopic pattern, and dermoscopic pigmented structures (network, globules, and peripheral streaks) were readily correlated between the in vivo and ex vivo images for 2 melanomas and 4 dysplastic nevi. Blood vessels were not observed in the ex vivo dermoscopic images, which limited their correlation with the in vivo dermoscopic images for basal cell carcinoma. CONCLUSIONS: Dermoscopy can be applied to fixed tissues, with findings comparable to those of in vivo examination. This observation may serve as the first step toward using dermoscopy to guide tissue sectioning in gross pathology.

Curcumin reduces burn progression in rats.

OBJECTIVES: Cutaneous burns are dynamic injuries with a central zone of necrosis surrounded by a zone of ischemia. Conversion of this ischemic zone to full necrosis over the days following injury is due in part to highly reactive oxygen radicals. Curcumin is a component of the Oriental spice turmeric that has been shown to have antioxidant and antiapoptotic properties. The authors hypothesized that treatment of burns with curcumin would reduce the conversion of the ischemic zone to full necrosis. METHODS: This was a randomized controlled experiment. Twenty Sprague-Dawley rats were used. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 x 20-mm full-thickness burns separated by three 5 x 20-mm unburned interspaces (zone of ischemia). Animals were randomized to curcumin or vehicle by oral gavage 30 minutes before injury and at 24, 48, and 72 hours after injury. Wounds were observed at one, two, and three days after injury for visual evidence of necrosis in the unburned interspaces. Full-thickness biopsy specimens from the interspaces were evaluated with hematoxylin and eosin staining seven days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi-square tests. RESULTS: Forty comb burns with 120 unburned interspaces were created, evenly distributed between curcumin and vehicle alone. The percentage of interspaces that progressed to full-thickness necrosis at one, two, three, and seven days after injury in the curcumin and vehicle groups were 30% versus 63% (p = 0.003), 30% versus 70% (p < 0.001), 63% versus 95% (p = 0.02), and 63% versus 95% (p = 0.02), respectively. CONCLUSIONS: Pretreatment of rats with oral curcumin followed by once-daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.

Atypical fibroxanthoma in a young woman: An unusual case presentation.

Atypical fibroxanthoma (AFX) is an uncommon neoplasm, identified as a spindle cell tumour that is generally found in elderly patients on sun-exposed areas. The majority of cases of AFX are benign, and metastasis is a rare phenomenon. The first case in the literature of AFX is described in a young woman with no previous risk factors who presented with a three-month history of an enlarging nodule of the left nasal alar. Excision showed the lesion to be composed of hyperchromatic, pleomorphic, vacuolated spindle cells and multinucleated giant cells. The tumour cells stained positive for macrophage-histiocyte antigen alpha(1)-antitrypsin, neurokinin-1, CD68 and alpha(1)-antichymotrypsin. The present case report highlights the importance of correct diagnosis for AFX with adequate excision and by considering the histopathology and immunohisto-chemistry of its clinical differential diagnosis.