Epidemiology, Risk Factors and Outcomes of Pneumomediastinum in Patients with Coronavirus Disease 2019: A Case-Control Study.

Background: Since the beginning of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, pneumomediastinum has been reported in patients with COVID-19 pneumonia and acute respiratory distress syndrome. It has been suggested that pneumomediastinum may portend a worse outcome in such patients although no investigation has established this association definitively. Research Question: We hypothesized that the finding of pneumomediastinum in the setting of COVID-19 disease may be associated with a worse clinical outcome. The purpose of this study was to determine if the presence of pneumomediastinum was predictive of increased mortality in patients with COVID-19. Study Design and Methods: A retrospective case-control study utilizing clinical data and imaging for COVID-19 patients seen at our institution from 3/7/2020 to 5/20/2020 was performed. 87 COVID-19 positive patients with pneumomediastinum were compared to 87 COVID-19 positive patients without pneumomediastinum and to a historical group of patients with pneumomediastinum during the same time frame in 2019. Results: The incidence of pneumomediastinum was increased more than 6-fold during the COVID-19 pandemic compared to 2019 (P = <.001). 1.5% of all COVID-19 patients and 11% of mechanically ventilated COVID-19 patients at our institution developed pneumomediastinum. Patients who developed pneumomediastinum had a significantly higher PEEP and lower P/F ratio than those who did not (P = .002 and .033, respectively). Pneumomediastinum was not found to be associated with increased mortality (P = .16, confidence interval [CI]: 0.89-2.09, 1.37). The presence of concurrent pneumothorax at the time of pneumomediastinum diagnosis was associated with increased mortality (P = .013 CI: 1.15-3.17, 1.91). Conclusion: Pneumomediastinum is not independently associated with a worse clinical prognosis in COVID-19 positive patients. The presence of concurrent pneumothorax was associated with increased mortality.

The Rise and Fall of the Pale Puffy Lower Eyelid Pillow.

This case series demonstrates an exaggerated form of the clinical presentation of a known distressing late complication of retained hyaluronic acid filler – the “pale puffy pillow.” This presentation is often, unfortunately for the patient, misdiagnosed as festoons. However, the correction with liberal hyaluronidase is simple. Additionally, we have demonstrated that ablative fractional carbon dioxide laser resurfacing is an excellent tool that may be utilized after hyaluronidase to correct the residual skin laxity.J Drugs Dermatol. 20(4):475-476. doi:10.36849/JDD.5509.

How Point-of-Care Ultrasound Led to a Diagnosis of May-Thurner Syndrome.

A 65-year-old man with a history of a left-sided inguinal hernia presented with three days of left-sided groin pain worsened with exertion and fatigue. The patient was afebrile but tachycardic, and physical examination revealed a tender, erythematous immobile bulge in his left groin. Laboratory studies revealed leukocytosis. Lymphadenopathy secondary to infectious or inflammatory etiology was suspected. However, point-of-care ultrasound (POCUS) identified extensive deep vein thrombosis (DVT) of the lower left limb. Follow-up imaging revealed this to be secondary to May-Thurner syndrome, a mechanical compression of an iliocaval vein against the lumbar vertebrae by a common iliac artery. This report demonstrates how POCUS can be used to identify lower extremity DVT, thereby expediting diagnosis and treatment and potentially preventing complications.

Pulsed Dye Laser Treatment of Port-Wine Stains in Infancy Without the Need for General Anesthesia.

Importance: Recent concerns regarding repetitive use of general anesthesia in children younger than 3 years have placed greater importance on the controversy surrounding the timing of the initiation of port-wine stain (PWS) laser treatment. Objective: To evaluate the use of PWS treatments at the age of 1 year or younger in the office setting without general anesthesia. Design, Setting, and Participants: Retrospective cohort study based on medical record reviews at a single, high-volume laser center for children who started pulsed dye laser treatment at the age of 1 year or younger for their PWS between 2000 and 2017. The data cutoff was at 1 year after the initial treatment to have comparable data points. Main Outcomes and Measures: The primary outcome was improvement of PWSs using before and after photographs, which were reviewed by 4 physicians independently and graded using the following 5-point visual analog scale (VAS): poor (grade 1: 0%-25% improvement), fair (grade 2: 26%-50% improvement), good (grade 3: 51%-75% improvement), excellent (grade 4: 76%-99% improvement), and complete (grade 5: 100% improvement) clearance. Results: Of the 197 patients (73 [37.1%] boys; 124 [62.9%] girls), most (149 [75.6%]) had facial lesions. The mean age at the time of first treatment was 3.38 months (range, 5-355 days) and the mean number of treatments was 9.8 (range, 2-23; median, 10). Per the mean physician VAS grading of 197 patients, 51 patients (25.9%) showed 100% clearance (mean [range] VAS score of 4.78 [4.5 - 5]); 81 patients (41.1%) showed 76 to 99% improvement (mean [range] VAS score of 3.91 [3.5 to <4.5]); 44 patients (22.3%) showed 51% to 75% improvement (mean [range] VAS score of 2.86 [2.5 to <3.5]); 13 patients (6.6%) showed 26% to 50% improvement (mean [range] VAS score of 2.12 [1.5 to <2.5]); and 8 patients (4.1%) showed 0 to 25% improvement (mean [range] VAS score of 0.78 [0 to <1.5]). The presence of a V1 (first branch of the trigeminal nerve [ophthalmic nerve]) lesion was associated with a statistically significantly higher clearance rate by a VAS grade of 0.55 (95% CI, 0.25-0.84; P < .001). The mean (SD) VAS grade for all patients was 3.65 (1.26), corresponding to excellent clearance. None of the patients experienced scarring or permanent pigmentary change. Conclusions and Relevance: In this study, treatment of PWSs in infancy was both safe and effective. Early intervention allows for treatment without general anesthesia, maximizing the chance to achieve clearance before school age and thereby minimizing the negative outcome of PWSs for both the patient and the family.

Micrographic Surgery and Dermatologic Oncology Fellowship Selection Criteria.

BACKGROUND: Obtaining a fellowship position for Micrographic Surgery and Dermatologic Oncology (MSDO) is becoming very competitive. Applicant qualities desired by MSDO fellowship directors have not been previously explored in a systematic way. OBJECTIVE: To characterize the prevailing practices of selecting MSDO fellows. METHODS AND MATERIALS: Cross-sectional study based on an anonymous online survey of MSDO fellowship directors. RESULTS: There were 34 completed surveys. Selection criteria with the highest importance to fellowship directors were the ability to work well and get along with others, interview, work ethic, and letter of recommendation from the Mohs micrographic surgery director at the applicant's residency. The criteria with the lowest importance were advanced degrees, medical licensing examination scores, and membership in Alpha Omega Alpha. Specific applicant factors that were looked upon most positively by fellowship directors include applicant from own institution and applicant's personal reasons and circumstances, whereas factors that were most unfavorable include applicant's desire to practice in the same city/area as the fellowship location and graduate of foreign medical school. CONCLUSION: Although variations existed, MSDO fellowship directors collectively placed greater importance on criteria that reflect interpersonal skills than on objective measures of academic performance, which highlights the importance of "fit."

Efficient and self-adaptive in-situ learning in multilayer memristor neural networks.

Memristors with tunable resistance states are emerging building blocks of artificial neural networks. However, in situ learning on a large-scale multiple-layer memristor network has yet to be demonstrated because of challenges in device property engineering and circuit integration. Here we monolithically integrate hafnium oxide-based memristors with a foundry-made transistor array into a multiple-layer neural network. We experimentally demonstrate in situ learning capability and achieve competitive classification accuracy on a standard machine learning dataset, which further confirms that the training algorithm allows the network to adapt to hardware imperfections. Our simulation using the experimental parameters suggests that a larger network would further increase the classification accuracy. The memristor neural network is a promising hardware platform for artificial intelligence with high speed-energy efficiency.

Successful and safe use of Q-switched lasers in the treatment of nevus of Ota in children with phototypes IV-VI.

OBJECTIVE: Nevus of Ota represents congenital dermal melanocytosis in a trigeminal distribution, most commonly occurring in Asian individuals and other individuals with skin of color. Evidence suggests early treatment is beneficial. Multiple reports have shown efficacy and safety of Q-switched laser treatment in adults. There is little data on children and in non-Asian skin types. This series was done to demonstrate safe and effective use of Q-switched laser therapy in children of multiple skin types. STUDY DESIGN: Retrospective case series. METHODS: This was a chart review of patients under 18 years old who presented to our practice from 2002 to 2015 with a clinical diagnosis of nevus of Ota who were treated with Q-switched lasers (694 and 1,064 nm). Patients were treated without the use of general anesthesia or sedation, and corneal shields were used in appropriate cases. Percentage of improvement as well as side effects were rated by five physicians independently. Improvement, when present, was rated in quartiles (1-25%, 26-50%, 51-75%, and 76-100% improvement). RESULTS: Twenty-four children were included. The average age at the start of treatment was 3.9 years old (range of 3 months to 12.4 years), and patients had Fitzpatrick skin types IV through VI. The mean number of treatments was 9.3. Assessment revealed excellent response (76-100% improvement) in 70% of patients and good to excellent response (51-100% improvement) in 86%. Two patients (8%) had post-inflammatory hyperpigmentation, one of whom also had focal hypopigmentation. CONCLUSION: Treatment of nevus of Ota with Q-switched lasers in children with skin of color, without general anesthesia or sedation, is safe and effective. Early intervention should be encouraged for better efficacy and to prevent psychosocial distress in later childhood and adulthood. Lasers Surg. Med. 50:56-60, 2018. © 2017 Wiley Periodicals, Inc.

A novel true random number generator based on a stochastic diffusive memristor.

The intrinsic variability of switching behavior in memristors has been a major obstacle to their adoption as the next generation of universal memory. On the other hand, this natural stochasticity can be valuable for hardware security applications. Here we propose and demonstrate a novel true random number generator utilizing the stochastic delay time of threshold switching in a Ag:SiO2 diffusive memristor, which exhibits evident advantages in scalability, circuit complexity, and power consumption. The random bits generated by the diffusive memristor true random number generator pass all 15 NIST randomness tests without any post-processing, a first for memristive-switching true random number generators. Based on nanoparticle dynamic simulation and analytical estimates, we attribute the stochasticity in delay time to the probabilistic process by which Ag particles detach from a Ag reservoir. This work paves the way for memristors in hardware security applications for the era of the Internet of Things.Memristors can switch between high and low electrical-resistance states, but the switching behaviour can be unpredictable. Here, the authors harness this unpredictability to develop a memristor-based true random number generator that uses the stochastic delay time of threshold switching.

Response to Laser Treatment of Café au Lait Macules Based on Morphologic Features.

Importance: Response to laser treatment for café au lait macules (CALMs) is inconsistent and difficult to predict. Objective: To test the hypothesis that irregularly bordered CALMs of the "coast of Maine" subtype respond better to treatment than those of the smooth-bordered "coast of California" subtype. Design, Setting, and Participants: This retrospective case series included patients from 2 multiple-clinician US practices treated from 2005 through 2016. All patients had a clinical diagnosis of CALM and were treated with a Q-switched or picosecond laser. A total of 51 consecutive patients were eligible, 6 of whom were excluded owing to ambiguous lesion subtype. Observers were blinded to final patient groupings. Exposures: Treatment with 755-nm alexandrite picosecond laser, Q-switched ruby laser, Q-switched alexandrite laser, or Q-switched 1064-nm Nd:YAG laser. Main Outcomes and Measures: Main outcome was grade in a visual analog scale (VAS) consisting of 4 levels of treatment response: poor (grade 1, 0%-25% improvement), fair (grade 2, 26%-50% improvement), good (grade 3, 51%-75% improvement), and excellent (grade 4, 76%-100% improvement). Results: Forty-five patients were included in the series, 19 with smooth-bordered lesions and 26 with irregularly bordered lesions. Thirty-four (76%) of the participants were female; 33 (73%) were white; and the mean age at the time of laser treatment was 14.5 years (range, 0-44 years). Smooth-bordered lesions received a mean VAS score of 1.76, corresponding to a fair response on average (26%-50% pigmentary clearance). Irregularly bordered lesions received a mean VAS score of 3.67, corresponding to an excellent response on average (76%-100% clearance) (P < .001). Conclusions and Relevance: CALMs with jagged or ill-defined borders of the coast of Maine subtype tend to respond well to laser treatment, whereas those with smooth and well-defined borders of the coast of California subtype tend to have poor response. Clinicians using Q-switched or picosecond lasers to treat CALMs can use morphologic characteristics to help predict response and more effectively manage patient expectations.

An Anatomical Approach to Evaluating and Treating Cellulite.

Cellulite is the common rippling or dimpling of skin of the thighs and buttocks of women, formed from a confluence of skin laxity, tethering fibrous septa, and fat herniation. We describe an anatomical approach to evaluating the cellulite patient and selecting the best treatment from among available non-invasive, minimally invasive, and invasive therapies. It is crucial to consider the anatomy of the patient and the morphology of cellulite while choosing a treatment. Diffuse rippling represents increased adiposity and/or increased skin laxity which may stand to benefit from lipolytic and skin tightening modalities. Dimpling represents tethering by fibrous septa which may stand to improve from subcision by minimally invasive devices such as Cell na. Patients with both morphologies may be treated with a combination of treatments or Cellulaze. Careful evaluation of the patient can help identify the best therapeutic strategy. J Drugs Dermatol. 2017;16(1):58-61..

Radiographic imaging for skin cancer.

Radiographic imaging is important for the full evaluation of high-risk cutaneous tumors. The correct modality should be chosen based on tumor subtype and clinical question. Locally advanced tumors may require imaging to evaluate the extent of disease, such as bony involvement, orbital infiltration, or perineural invasion. Tumors at high risk for regional and distant metastasis require imaging to identify local and distant tumor burden.

An animal explant model for the study of human cutaneous squamous cell carcinoma.

We established a human tissue explant model to facilitate study of cutaneous squamous cell carcinoma. We accomplished this by implanting debulked SCC, from surgical discard, into nude rats. Human SCC remained viable and continued to proliferate for at least 4 weeks and showed evidence of neovascularization. At 4 weeks, SCC implants showed a trend toward increased PCNA positive cells compared to fresh SCC cells/mm(2) tissue) supporting continued proliferation throughout engraftment. Von Willebrand's Factor (VWF) positive cells were found within implants and likely represented rat vessel neovascularization. Human Langerhans' (Langerin+) cells, but no T cells (CD3+, CD8+, FoxP3+), macrophages (CD163), or NK cells (NKp46), were present in SCC implants at 4 weeks. These findings support the possibility that LCs fail to migrate from cutaneous SCC and thus contribute to lack of effective antitumor response. Our findings also provide a novel model system for further study of primary cutaneous SCC.

CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell carcinoma.

OBJECTIVE: To characterize the presence of CD200 and CD200 receptor (CD200R) in the human cutaneous squamous cell carcinoma (SCC) microenvironment and to define a possible role for the CD200 axis in immune evasion by SCC. DESIGN: Gene expression in SCC vs normal skin was studied. Laser capture microdissection was used to determine differential expression of CD200 in normal skin vs actinic keratosis vs SCC in situ vs invasive SCC. Immunofluorescence microscopy was used to define expression of CD200R on macrophages, myeloid dendritic cells, natural killer cells, and T cells in SCC vs normal skin. The effects of SCC supernatant on induction of CD200 in human blood endothelial cells was also examined. SETTING: Academic Medical Center with an established Section of Mohs and Dermatologic Surgery and an active Cutaneous Biology Research Program. PARTICIPANTS: Surgical discard tissue from deidentified patients and samples of normal skin from healthy volunteers were used in this study. MAIN OUTCOME MEASURES: Expression of CD200 on SCC-associated blood vessels; expression of CD200 receptor on SCC-associated macrophages and T cells; and induction of CD200 on endothelial cells by SCC supernatants. RESULTS: CD200 gene and message were upregulated in SCC stroma. Immunostaining revealed a higher number of CD200(+) cells in SCC stroma than in normal dermis (180.8 cells/mm(2) vs 24.6 cells/mm(2)) (P<.01). CD200 was further identified mainly on blood vessel endothelium in SCC. Tumor supernatant was able to induce CD200 expression on human dermal blood endothelial cells in culture. CD200R was identified on macrophages and dendritic cells in SCC microenvironment. CONCLUSIONS: CD200 expression on local blood vessels may promote tumor progression by suppressing CD200R myeloid cells during diapedesis. These data highlight a previously unrecognized mechanism of immune evasion by SCC and may provide guidance for the development of targeted therapy.

Combined use of laser capture microdissection and cDNA microarray analysis identifies locally expressed disease-related genes in focal regions of psoriasis vulgaris skin lesions.

Psoriasis vulgaris is a complex disease characterized by alterations in growth and differentiation of epidermal keratinocytes, as well as a marked increase in leukocyte populations. Lesions are known to contain alterations in messenger RNAs encoding more than 1,000 products, but only a very small number of these transcripts has been localized to specific cell types or skin regions. In this study, we used laser capture microdissection (LCM) and gene array analysis to study the gene expression of cells in lesional epidermis (EPI) and dermis, compared with the corresponding non-lesional regions. Using this approach, we detected >1,800 differentially expressed gene products in the EPI or dermis of psoriasis lesions. These results established sets of genes that are differentially expressed between epidermal and dermal compartments, as well as between non-lesional and lesional psoriasis skin. One of our findings involved the local production of CCL19, a lymphoid-organizing chemokine, and its receptor CCR7 in psoriatic dermal aggregates, along with the presence of gene products LAMP3/DC-LAMP and CD83, which typify mature dendritic cells (DCs). Gene expression patterns obtained with LCM and microarray analysis along with T-cell and DC detection by immune staining suggest a possible mechanism for lymphoid organization via CCL19/CCR7 in diseased skin.

Mathematical modeling and frequency gradient analysis of cellular and vascular invasion into integra and strattice: toward optimal design of tissue regeneration scaffolds.

BACKGROUND: Rapid, effective host cell invasion and vascularization is essential for durable incorporation of avascular tissue-replacement scaffolds. In this study, the authors sought to qualitatively and quantitatively determine which of two commercially available products (i.e., Strattice and Integra) facilitates more rapid cellular and vascular invasion in a murine model of graft incorporation. METHODS: Integra and Strattice were implanted subcutaneously into the dorsa of C57BL/6 mice; harvested after 3, 7, or 14 days; and stained with hematoxylin and eosin, 4',6-diamidino-2-phenylindole, and immunohistochemical stains for CD31 and α-smooth muscle actin. Exponential decay equations describing cellular invasion through each layer were fit to each material/time point. Mean cell density and cell frequency maps were created denoting extent of invasion by location within the scaffold. RESULTS: Qualitative analysis demonstrated extensive cellular infiltration into Integra by 3 days and increasing over the remaining 14 days. Invasion of Strattice was sparse, even after 14 days. α-Smooth muscle actin immunohistochemistry revealed blood vessel formation within Integra by 14 days but no analogous neovascularization in Strattice. Mean decay equations for Integra and Strattice were y = 76.3(0.59) and y = 75.5(0.33), respectively. Both cell density measurements and frequency mapping demonstrated that, at all time points, Integra manifested a greater density/depth of cellular invasion when compared with Strattice. CONCLUSIONS: These data confirm empiric clinical observations that Integra is more rapidly invaded than Strattice when placed in a suitable host bed. A remnant microvasculature template is not sufficient for effective cellular ingrowth into an artificial tissue construct. These findings provide insight into means for improving future dermal replacement products.

Mohs surgery for squamous cell carcinoma.

Cutaneous squamous cell carcinoma (SCC) is the second most common human cancer and can behave aggressively. Mohs micrographic surgery offers the highest cure rates for high-risk SCCs and is particularly useful for SCCs on challenging anatomic sites.

Tumor-associated macrophages in the cutaneous SCC microenvironment are heterogeneously activated.

Tumor-associated macrophages (TAMs) may have an important role in tumor immunity. We studied the activation state of TAMs in cutaneous SCC, the second most common human cancer. CD163 was identified as a more abundant, sensitive, and accurate marker of TAMs when compared with CD68. CD163(+) TAMs produced protumoral factors, matrix metalloproteinases 9 and 11 (MMP9 and MMP11), at the gene and protein levels. Gene set enrichment analysis (GSEA) was used to evaluate M1 and M2 macrophage gene sets in the SCC genes and to identify candidate genes in order to phenotypically characterize TAMs. There was coexpression of CD163 and alternatively activated "M2" markers, CD209 and CCL18 (chemokine (C-C motif) ligand 18). There was enrichment for classically activated "M1" genes in SCC, which was confirmed in situ by colocalization of CD163 and phosphorylated STAT1 (signal transducer and activator of transcription 1), IL-23p19, IL-12/IL-23p40, and CD127. Also, a subset of TAMs in SCC was bi-activated as CD163(+) cells expressed markers for both M1 and M2, shown by triple-label immunofluorescence. These data support heterogeneous activation states of TAMs in SCC, and suggest that a dynamic model of macrophage activation would be more useful to characterize TAMs.

Hydrogen sulfide protects against ischemia-reperfusion injury in an in vitro model of cutaneous tissue transplantation.

BACKGROUND: Ischemia-reperfusion injury (IRI) is a source of morbidity and mortality in many clinical scenarios, and has as one of its many consequences the induction of cellular apoptosis. Hydrogen sulfide (H2S) may decrease cellular metabolism in a reversible, nontoxic manner. An in vitro model of cutaneous tissue transplantation was developed to assess whether H2S could ameliorate cellular injury caused by IRI. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with media containing NaHS (0, 10 microM, 100 microM, or 1 mM) and exposed to normoxia (21% oxygen), hypoxia (1%), or anoxia (0%). Cells were then returned to normoxia, and apoptosis was quantified using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Fibroblasts (3T3s) were treated with H2S and exposed to anoxia in a similar fashion. RESULTS: Treatment with H2S resulted in a significant decrease in apoptosis in HUVECs and 3T3s subjected to IRI. Toxicity of H2S was not observed, although the protective effect was less evident at higher doses. CONCLUSION: This is the first study to examine H2S and the cellular components of cutaneous flaps in the setting of IRI. Our results demonstrate that H2S significantly decreases apoptosis in vitro in the setting of IRI. These data suggest H2S may mitigate IRI in vivo, and, therefore, has potential as a therapy for improving tissue survivability in clinical scenarios.