Background The coronavirus disease 2019 (COVID-19) pandemic has affected 18 million people and killed over 690,000 patients. Although this virus primarily causes respiratory symptoms, an increasing number of cutaneous manifestations associated with this disease have been reported. Objective The aim of this review was to collate and categorize the dermatologic findings reported in patients with COVID-19 and identify specific lesions that may facilitate diagnosis and prognostication. Methods An evidence-based review of the PubMed database was conducted on 14 May, 2020 using the search terms "Covid-19 skin," "Covid-19 rash," "Covid-19 exanthem," and "Covid-19 chilblains." Peer-reviewed publications containing original COVID-19 patient cases and a discussion of the associated cutaneous findings were included in the analysis. Results The literature search identified 115 records, of which 34 publications describing 996 patients with dermatologic conditions were included. Case reports (n = 15), case series (n = 13), and observational prospective studies (n = 4) were the most common publication types. Acral lesions resembling pseudo-chilblains were the most frequent lesion identified (40.4% of cases), appearing in young adults (mean age, 23.2 years) after the onset of extracutaneous COVID-19 symptoms (55/100 patients). Erythematous maculopapular rashes affected 21.3% of patients, most frequently impacting middle-aged adults (mean age, 53.2 years) and occurring at the same time as non-cutaneous symptoms (110/187 patients). Vesicular rashes affected 13.0% of patients, appearing in middle-aged adults (mean age, 48.3 years) after the onset of other symptoms (52/84 patients). Urticarial rashes affected 10.9% of patients, appearing in adults (mean age, 38.3 years) and occurring at the same time as non-cutaneous symptoms (46/78 patients). Vascular rashes resembling livedo or purpura were uncommon (4% of cases), appearing in elderly patients (mean age, 77.5 years) and occurring at the same time as non-cutaneous COVID-19 symptoms (18/29 patients). Erythema multiforme-like eruptions, although infrequent (3.7% of cases), affected mostly children (mean age, 12.2 years). Conclusions Vesicular rashes may suggest an initial diagnosis of COVID-19, acral lesions may be most appropriate for epidemiological uses, and vascular rashes may be a useful prognostic marker for severe disease. As a potential correlate to disease severity, prognosis, or infectibility, it is critical that all healthcare professionals be well versed in these increasingly common cutaneous manifestations of COVID-19.

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Purpose-Classical measures of vessel morphology including diameter and density are employed to study microvasculature in endothelial membrane labeled mice. These measurements prove sufficient for some studies; however they are less well suited for quantifying changes in microcirculatory networks lacking hierarchical structure. We demonstrate automated multifractal analysis and lacunarity may be used with classical methods to quantify microvascular morphology.Methods-We present an automated extraction tool with a processing pipeline to characterize 2D representations of 3D microvasculature, using multifractal analysis and lacunarity. We apply our analysis on four tissues and the hyaloid vasculature during remodeling.Results-We found that the vessel networks analyzed have multifractal geometries and that kidney microvasculature has the largest fractal dimension and the lowest lacunarity compared to microvasculature networks in the cortex, skin, and thigh muscle. Also, we found that during hyaloid remodeling, there were differences in multifractal spectra reflecting the functional transition from a space filling vasculature which nurtures the lens to a less dense vasculature as it regresses, permitting unobstructed vision.Conclusion-Multifractal analysis and lacunarity are valuable additions to classical measures of vascular morphology and will have utility in future studies of normal, developing and pathological tissues.

The field of tissue engineering is severely limited by a lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent nonspecific cell adhesion, thus providing a "blank slate", which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to the widespread effects of PDGF in the body and a half-life of only 30 min in circulating blood, immobilization of PDGF-BB may be necessary. In this work bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on two-dimensional modified surfaces, migration in three-dimensional (3D) degradable hydrogels and angiogenesis in a mouse cornea micro-pocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized fibroblast growth factor-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels compared with the presentation of each factor alone. When a co-culture of endothelial cells and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response compared with soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering.

Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled micro-vascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo.

Background Nipple-sparing mastectomy (NSM) is appropriate for selected patients with early-stage breast cancer or high breast cancer risk. However, the rate of nipple necrosis after NSM is relatively high (10% to 30%). No study has specifically evaluated whether clinical and technical factors contribute to nipple necrosis after NSM. The objectives of this study were to determine the impact of clinicopathologic and surgical variables on rates of partial and total nipple necrosis after NSM and to compare overall complication rates between NSM and skin-sparing mastectomy (SSM). Methods The study included 233 cases, 113 had NSM and immediate breast reconstruction and 120 matched (for disease stage, comorbidities, and age) cases of SSM and immediate reconstruction performed at our institution from September 2003 through May 2011. Complications were analyzed using the Fisher’s exact test, and in the NSM group, clinicopathologic and surgical variables were analyzed using Rao-Scott chi-squared tests for relationship with partial or total nipple necrosis. Results The overall complication rate was 28% for NSM and 27% for SSM (p>0.99). In patients who did not have axillary surgery (those undergoing risk-reducing mastectomy), the overall rate of complications was significantly higher in the NSM group than in the SSM group (26% versus 9%; p=0.06). However, in patients who had axillary surgery (either sentinel lymph node biopsy or axillary lymphadenectomy), the overall complication rate did not differ between the two groups. For NSM, the overall incidence of any (partial or total) nipple necrosis was 20%. There were only 2 cases (2%) with total necrosis. Larger breasts (C cup or larger) were associated with a higher rate of nipple necrosis (34% for C cup; 6% for A and B cup; p=0.003). Smoking (p=0.08) and vascular comorbidities (p=0.09) did not reach statistical significance as predictors of nipple necrosis. The other factors analyzed were not predictors of nipple necrosis. Conclusions We found no significant difference in the overall incidence of complications in patients who have NSM compared to those who have SSM. Interestingly, the exclusion of axillary lymphatic surgery in patients undergoing risk-reducing NSM for high breast cancer risk did not decrease the incidence of complications, probably because of the inherent technical complexity of performing NSM in and of itself. Although partial nipple necrosis did occur quite frequently (19%), total nipple necrosis after NSM occurred infrequently (2%). Importantly, patients with breast size of C cup or larger had an increased risk for nipple necrosis after NSM and immediate breast reconstruction. Clinical Level of Evidence Therapeutic, III.

Instagram use by plastic surgery integrated programs continues to grow exponentially, and programs are appropriately using the platform. Active use of the resident social media results in increased influence. Resident use of social media has many benefits. We propose social media guidelines for plastic surgery trainees and advocate for continued appropriate use and autoregulation by plastic surgery trainees.

The formation of a microvasculature is regulated in large part by cell-cell interactions. Ephrins and their Eph receptors mediate cell adhesion, repulsion, and migration, all critical processes in angiogenesis. 1 Here, we use a covalently immobilized ephrinA1, conjugated to poly(ethylene glycol), to induce vessel formation both in vitro and in vivo in poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Human umbilical vein endothelial cell (HUVEC) tubulogenesis in matrix metalloproteinase- sensitive hydrogels was visualized from 6 hours to 7 days in response to three different concentrations of PEG-ephrinA1. The deposition of extracellular matrix proteins collagen IV and laminin that stabilize tubule formation were imaged, quantified, and found to be dependent upon PEG-ephrinA1 concentration. To confirm the importance of the EphA2-ephrinA1 interaction in tubule formation, soluble EphA2 was used to disrupt the EphA2-ephrinA1 interaction between a co-culture of HUVEC and human brain vascular pericyte cells. HUVECs seeded onto PEGDA hydrogels displayed a dose- dependent reduction in tubule formation in response to the soluble EphA2. Finally, hydrogels with releasable platelet derived growth factor (PDGF), immobilized RGDS, and covalently immobilized PEG-ephrinA1 were implanted into the mouse cornea micropocket. These hydrogels induced a more robust vascular response with an increase in vessel density as compared to hydrogels with releasable PDGF alone. As such, PEG-ephrinA1 may represent a promising molecule to regulate cell adhesion and migration for formation of a microvasculature in tissue engineered constructs.