Nevus Spilus With Dermatoheliosis: A Histologic Mimicker of Melanoma in Situ at Melanoma Excision Margins.

ABSTRACT: Nevus spilus, or speckled lentiginous nevus, is a relatively common lesion that presents at birth or in early childhood. It consists of a background tan patch, which appears similar to a café au lait macule or lentigo simplex on histology, studded with various types of nevi. Rarely, these nevi can undergo malignant transformation to melanoma. When melanoma develops within a heavily photodamaged nevus spilus, evaluating excision margins may be challenging because the combined histologic features of nevus spilus and severe dermatoheliosis can mimic melanoma in situ. We report a case of an elderly man with extensive sun damage who developed malignant melanoma within an occult nevus spilus, resulting in multiple excisions with false-positive margins.

Epidemiology of distal radius fractures: Elucidating mechanisms, comorbidities, and fracture classification using the national trauma data bank.

BACKGROUND: An update on the epidemiology of distal radius fractures in the United States is necessary, particularly as the elderly population grows. Additionally, age and frailty have been associated with complications following surgical fixation of DRFs. Herein, we utilize the National Trauma Data Bank, a robust nationwide resource, to investigate the relationship between demographics, comorbidities, injury and fracture characteristics, and admission details. METHODS: Patients with isolated distal radius fractures were identified from the National Trauma Data Bank (2016-2019) according to ICD-10 codes. Univariate and multivariate regressions were conducted to determine independent risk factors for bilateral fractures, displaced fractures, open fractures, as well as length of hospital stay and adverse discharge disposition for patients undergoing inpatient surgical fixation. RESULTS: The incidence of DRFs was 3.6/1,000 trauma-related emergency department visits and 10.8/1,000 upper extremity traumas. Trauma mechanism was significantly associated with displaced and open fractures. Age (OR 1.01, 95% CI 1.01-1.01), BMI (OR 1.02, 95% CI 1.01-1.02), smoking (OR 1.34, 95% CI 1.15-1.57), and alcohol level (trace: OR 2.18, 95% CI 1.41-3.29; intoxicated: OR 2.20, 95% CI 1.63-2.95) were significantly associated with open fractures. Machinery (ß=2.04, 95% CI 1.00-3.08) and MVT (ß=0.39, 95% CI 0.08-0.69) mechanisms were independent risk factors for longer length of stay. mFI-5 was an independent risk factor, in a stepwise fashion, for both length of stay and adverse discharge disposition. CONCLUSIONS: High-energy mechanisms and risk factors for poor skin quality were significantly associated with open fractures. mFI-5 was an independent risk factor for longer length of stay and non-routine discharges in patients of all ages, despite controlling for other comorbidities, unrelated complications, and mechanism of injury. Trauma mechanism was an independent risk factor for prolonged length of stay only, particularly in patients younger than 65 years of age.

The First Successful Combined Full Face and Bilateral Hand Transplant.

BACKGROUND: Vascularized composite allotransplantation has redefined the frontiers of plastic and reconstructive surgery. At the cutting edge of this evolving paradigm, the authors present the first successful combined full face and bilateral hand transplant. METHODS: A 21-year-old man presented for evaluation with sequelae of an 80 percent total body surface area burn injury sustained after a motor vehicle accident. The injury included full face and bilateral upper extremity composite tissue defects, resulting in reduced quality of life and loss of independence. Multidisciplinary evaluation confirmed eligibility for combined face and bilateral hand transplantation. The operative approach was validated through 11 cadaveric rehearsals utilizing computerized surgical planning. Institutional review board and organ procurement organization approvals were obtained. The recipient, his caregiver, and the donor family consented to the procedure. RESULTS: Combined full face (i.e., eyelids, ears, nose, lips, and skeletal subunits) and bilateral hand transplantation (i.e., forearm level) was performed over 23 hours on August 12 to 13, 2020. Triple induction and maintenance immunosuppressive therapy and infection prophylaxis were administered. Plasmapheresis was necessary postoperatively. Minor revisions were performed over seven subsequent operations, including five left upper extremity, seven right upper extremity, and seven facial secondary procedures. At 8 months, the patient was approaching functional independence and remained free of acute rejection. He had significantly improved range of motion, motor power, and sensation of the face and hand allografts. CONCLUSIONS: Combined face and bilateral hand transplantation is feasible. This was the most comprehensive vascularized composite allotransplantation procedure successfully performed to date, marking a new milestone in plastic and reconstructive surgery for patients with otherwise irremediable injuries.

Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene.

To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes.

Deconvoluting subensemble chemical reaction kinetics of platinum-sulfur ligand exchange detected with single-molecule fluorescence microscopy.

The subensemble kinetics of a platinum-sulfur covalent chemical reaction at the solution/surface interface of a model industrial catalyst support was examined using single-molecule fluorescence microscopy (SMFM) and was found to exhibit biexponential first-order kinetic behavior. The observed kinetics was a convolution of the observation probability and chemical reaction rate. These results suggest that deconvolution strategies may be broadly important for obtaining accurate chemical reaction kinetics with SMFM.

Single-molecule imaging of platinum ligand exchange reaction reveals reactivity distribution.

Single-molecule fluorescence microscopy provided information about the real-time distribution of chemical reactivity on silicon oxide supports at the solution-surface interface, at a level of detail which would be unavailable from a traditional ensemble technique or from a technique that imaged the static physical properties of the surface. Chemical reactions on the surface were found to be uncorrelated; that is, the chemical reaction of one metal complex did not influence the location of a future chemical reaction of another metal complex.

Characterizing the infrared bands of aqueous soluble silicates.

A systematic study of the transition in silicate solutions from a solution containing a highly complex mixture of silicate species to one dominated by a single symmetric cubic octamer has been completed. Infrared and NMR results have been analyzed and compared with each other and literature values. The FT-IR band locations are dependent on many factors, particularly the dominant band near 1000 cm(-1). The analysis supports Dent Glasser's hypothesis that silica polymerization results from changes in distribution between the larger colloidal silica and intermediate sized anionic fraction rather than the continuous stepwise growth seen with organic polymerization. A constant value of silica monomer seen in all solutions independent of the complexity of the species or their distribution suggests equilibrium between the monomeric form and larger anions and polymers that is independent of their structure. No evidence is uncovered for specific silicate species dependent IR band assignments.

Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064.

Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

FXR agonist activity of conformationally constrained analogs of GW 4064.

Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

The inadequacy of punch-excised melanocytic lesions: sampling through the block for the determination of "margins".

BACKGROUND: Dermatopathologists often are asked by clinicians to report margins on punch excisions of melanocytic lesions. OBJECTIVE: We sought to determine the adequacy of surgical margins on melanocytic lesions submitted with intention of complete excision using punch removal technique. METHODS: We conducted prospective analysis of surgical margins on 266 consecutive patients who underwent attempted complete removal of 405 melanocytic nevi submitted as punch and fusiform excisions. RESULTS: Of 206 nonbisected punch excisions, 127 (62%) had final positive margins. Of 159 bisected punch excisions, 76 (48%) had final positive margins. Of 40 elliptical excisions, two (5%) had final positive margins. LIMITATIONS: Information on the perilesional rim of nonpigmented skin included in the excision was not available. CONCLUSIONS: Of punch excisions, 56% had positive margins. Importantly, 30% of these punch excised specimens were negative on initial levels but had positive margins after extensive sectioning, affirming that fusiform excisions are the preferred method to evaluate margins in melanocytic lesions.

Improved Diagnostic Accuracy of Periprosthetic Breast Infection: Novel Application of the Alpha Defensin-1 Biomarker.

Prompt, accurate diagnosis of breast implant infection is critical to minimizing patient morbidity. Bacterial culture false negative rate approaches 25%-30%, and better costeffective testing modalities are needed. Alpha defensin-1 (AD-1) is a neutrophil-mediated biomarker for microbial infection. With sensitivity/specificity of 97% and 96%, it has replaced culture as the preferred diagnostic modality for orthopedic periprosthetic infection, but has yet to be investigated in breast reconstruction. This pilot study compares the diagnostic performance of AD-1 to bacterial culture in suspected periprosthetic breast infection. METHODS: Patients with prosthetic breast reconstruction and suspected periprosthetic infection were prospectively studied. Implant pocket fluid was analyzed with gram stain and culture, AD-1 assay, and adjunctive markers. Demographics, operative history, prosthetic characteristics, and antibiotic exposure were collected, and diagnostic performance of each test was compared. RESULTS: Fifteen breasts with suspected periprosthetic breast infection were included, 10 (66.7%) of which were acutely infected. Gram stain correctly identified only 1 of 10 infections, whereas culture failed to identify 1 infection and reported equivocal/false-positives in 2 noninfected samples. AD-1, however, correctly classified all 15 samples. AD-1 exhibited 100% sensitivity and specificity, comparing favorably to culture (sensitivity: 90%, specificity: 60%), although this did not reach significance (P=0.22). Infected breasts also demonstrated significantly higher adjunctive marker levels compared to noninfected breasts. CONCLUSIONS: This study demonstrates the utility of AD-1 in diagnosing periprosthetic breast infection. Combining AD-1 with adjunctive inflammatory markers may allow more accurate, prompt detection of implant infection which may reduce morbidity and reconstructive failures.

Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064.

Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

Cutaneous ganglioneuroma associated with overlying hyperkeratotic epidermal changes: a report of 2 cases.

The occurrence of primary cutaneous ganglioneuroma is rare. We report 2 separate cases of primary cutaneous ganglioneuroma, both of which are associated with prominent overlying hyperkeratosis. The first case was in a 38-year-old woman with overlying verrucous keratosis. The second case was in a 93-year-old man with epidermal changes reminiscent of a seborrheic keratosis. Histologically, both lesions were composed of a proliferation of hyperplastic nerve fibers with spindled Schwann cells and axons with intermingled ganglion cells. Immunohistochemistry for neurofilament highlighted nerve fascicles; S100 protein displayed the associated Schwann cells, and neuron-specific enolase stained the interspersed ganglion cells. Variation in immunohistochemical staining was present between the 2 cases. A review of the literature demonstrates variable immunohistochemical staining of ganglion and Schwann cells in prior cases. Familiarity with these findings is important in establishing a diagnosis. The significance of the associated hyperkeratosis remains speculative.

Surgical management of digital ischemia caused by constriction band formation in a patient with ichthyosis vulgaris.

Ichthyosis is a broad and loosely defined group of hereditary and acquired disorders characterized by filaggrin dysfunction and impaired epidermal homeostasis that results in dry, scaly and thickened skin. Individuals with truncation mutations in the profilaggrin gene coding for filaggrin are strongly predisposed to severe forms of ichthyosis. The phenotypical expression of ichthyosis caused by the same genotypical mutation can vary considerably in severity and in regards to how much constricting scar tissue develops. Here, we report a case of digital ichthyosis threatening the neurovascular integrity to the small finger to discuss the importance of early diagnosis and role of Z-plasty flaps in the surgical treatment of constriction band formation.

Lipidized dermatofibromas and their relationship to serum lipids.

BACKGROUND: Lipidized dermatofibromas represent a rare variant of dermatofibroma that has been regarded as an incidental finding with no particular clinical significance. OBJECTIVE: The goal of this study was to investigate the relationship between lipidized dermatofibromas and patient age, anatomic location, and serum total cholesterol. METHODS: A retrospective case control format was used with an experimental group containing patients with biopsy-proven lipidized dermatofibromas and a control group containing patients with nonlipidized dermatofibromas. RESULTS: Ages in the experimental group ranged from 35 to 75 years with a mean value of 53 years whereas ages in the control group ranged from 27 to 72 years with a mean value of 48 years. A comparison between the mean of the ages between the two groups using the t test method showed no statistically significant difference (P = .09). Lesion location on the body was grouped into 4 sites: leg, thigh, trunk, and upper extremity. Of the 23 patients in the experimental group, 10 had lesions on the legs, 5 had lesions on the thighs, 2 had lesions on the trunk, and 5 had lesions on the upper extremities. Of the 41 patients in the control group, 15 had lesions on the legs, 7 had lesions on the thighs, 9 had lesions on the trunk, and 10 had lesions on the upper extremities. A comparison between the two groups showed no statistically significant difference (P = .60). In all, 16 of the 23 patients in the experimental group and 24 of the 41 patients in the control group were considered to have high cholesterol. A comparison showed no statistically significant difference between the cholesterol levels of the two groups (P = .38). LIMITATIONS: Limitations that we encountered during the study included the relative infrequency of lipidized dermatofibromas, limiting the number of patients in the study. In addition, medication histories and lipid levels on patients were not always available. In addition, we formed a control group from people who had their cholesterol checked often, which may cause them to have a higher average cholesterol than that of the general population. CONCLUSIONS: Our data show that lipidized dermatofibromas do not differ clinically from nonlipidized dermatofibromas in age distribution of patients, tumor location, or underlying serum lipid levels.

Impact of thorough block sampling in the histologic evaluation of melanomas.

OBJECTIVE: To determine if changes in histologic parameters obtained from intermittent sampling of the entire block correlated with differences in prognosis and management. DESIGN: Prospective analysis of skin biopsy specimens. SETTING: Skin pathology laboratory. Patients One hundred consecutive patients with an unequivocal diagnosis of melanoma. Interventions Two initial slides were prepared from serial sections of 5-mum thickness. When evaluation of the initial slide revealed melanoma, 5 additional slides were obtained by sectioning at levels through the entire block. Breslow depth, Clark level, ulceration, tumor infiltrating lymphocytes, vascular invasion, regression, presence of a precursor lesion, and histologic type of melanoma for the first slide and the additional 6 slides were analyzed and compared. RESULTS: Review of the additional 6 slides from level sectioning revealed a greater maximum tumor thickness than was evident from the original slide in 43% of the cases. In 10 of these cases, the new maximum tumor thickness measurements changed the surgical management of the patients. Ulceration was observed in 6% of cases on the initial slides, and an additional 3% of lesions were found to have ulceration on levels. The level of invasion was deeper than originally found in 10% of the cases. CONCLUSIONS: Level sectioning through an entire block of a melanoma specimen provides additional information in the classification and management of melanomas. Extensive block sampling will result in more accurate information regarding histologic parameters of melanoma, but the yield must be balanced with the extra cost of materials, time, labor, and the potential disadvantage of not retaining tissue for future use.