Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients.

BACKGROUND: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from long-standing adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Because obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature. OBJECTIVE: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD. METHODS: We compared microarrays and reverse transcription polymerase chain reaction (RT-PCR) of blood cells from 28 AD children (<5 years and within 6 months of disease onset) to healthy control blood cells. Differentially expressed genes (DEGs) in blood (fold change [FCH] > 1.2 and false discovery rate [FDR] < 0.05) were then compared with skin DEGs. RESULTS: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were up-regulated in early pediatric AD blood, whereas IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss [TEWL]), whereas Th2/Th17-induced interleukin (IL)-19 was positively correlated with SCORAD. Although a few RT-PCR-defined immune markers (IL-13/CCL22) were increased in blood, as previously also reported for skin, minimal overlap based on gene array DEGs was seen. CONCLUSION: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile; however, markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course, allergic comorbidity development, and response to systemic medications.

Silicone Breast Implant Surface Texture Impacts Gene Expression in Periprosthetic Fibrous Capsules.

BACKGROUND: Silicone breast implants with smooth outer shells are associated with higher rates of capsular contracture, whereas textured implants have been linked to the development of breast implant-associated anaplastic large cell lymphoma. By assessing the gene expression profile of fibrous capsules formed in response to smooth and textured implants, insight into the development of breast implant-associated abnormalities can be gained. METHODS: Miniature smooth or textured silicone implants were surgically inserted into female rats ( n = 10) and harvested for the surrounding capsules at postoperative week 6. RNA sequencing and quantitative polymerase chain reaction were performed to identify genes differentially expressed between smooth and textured capsules. For clinical correlation, the expression of candidate genes was assayed in implant capsules harvested from human patients with and without capsular contracture. RESULTS: Of 18,555 differentially expressed transcripts identified, three candidate genes were selected: matrix metalloproteinase-3 ( MMP3 ), troponin-T3 ( TNNT3 ), and neuregulin-1 ( NRG1 ). In textured capsules, relative gene expression and immunostaining of MMP3 and TNNT3 was up-regulated, whereas NRG1 was down-regulated compared to smooth capsules [mean relative fold change, 8.79 ( P = 0.0059), 4.81 ( P = 0.0056), and 0.40 ( P < 0.0001), respectively]. Immunostaining of human specimens with capsular contracture revealed similar gene expression patterns to those of animal-derived smooth capsules. CONCLUSIONS: An expression pattern of low MMP3 /low TNNT3 /high NRG1 is specifically associated with smooth implant capsules and human implant capsules with capsular contracture. The authors' clinically relevant breast implant rat model provides a strong foundation to further explore the molecular genetics of implant texture and its effect on breast implant-associated abnormalities. CLINICAL RELEVANCE STATEMENT: The authors have demonstrated that there are distinct gene expression profiles in response to smooth versus textured breast implants. Since surface texture may be linked to implant-related pathology, further molecular analysis of periprosthetic capsules may yield strategies to mitigate implant-related complications.

Sleep Apnea and Skin.

PURPOSE OF THE REVIEW: Skin disease is associated with obstructive sleep apnea (OSA) both epidemiologically and mechanistically. In this review we highlight conditions which have a well-established link to obstructive sleep apnea, such as psoriasis and atopic dermatitis. RECENT FINDINGS: We describe putative mechanistic links between OSA and skin disease involving inflammatory pathways, obesity, mechanical upper airways obstruction, and hypoxia. In the context of these mechanisms we describe specific skin conditions, and other conditions which are associated with both skin manifestations (including hair/nail findings) and OSA. The risks/ benefits of CPAP in the context of skin disease are also reviewed. SUMMARY: We conclude that further research is needed to understand the mechanisms behind the associations between OSA and skin disease. Given the frequent co-occurrence of OSA and skin conditions, there would be great benefit for OSA clinical trials to consider improvement in skin disease as an outcome measure.

Skin-interfaced biosensors for advanced wireless physiological monitoring in neonatal and pediatric intensive-care units.

Standard clinical care in neonatal and pediatric intensive-care units (NICUs and PICUs, respectively) involves continuous monitoring of vital signs with hard-wired devices that adhere to the skin and, in certain instances, can involve catheter-based pressure sensors inserted into the arteries. These systems entail risks of causing iatrogenic skin injuries, complicating clinical care and impeding skin-to-skin contact between parent and child. Here we present a wireless, non-invasive technology that not only offers measurement equivalency to existing clinical standards for heart rate, respiration rate, temperature and blood oxygenation, but also provides a range of important additional features, as supported by data from pilot clinical studies in both the NICU and PICU. These new modalities include tracking movements and body orientation, quantifying the physiological benefits of skin-to-skin care, capturing acoustic signatures of cardiac activity, recording vocal biomarkers associated with tonality and temporal characteristics of crying and monitoring a reliable surrogate for systolic blood pressure. These platforms have the potential to substantially enhance the quality of neonatal and pediatric critical care.

The color of skin: orange diseases of the skin, nails, and mucosa.

Cutaneous disease can present with lesions of all colors of the visible spectrum. Lesions of the skin, nail, and mucous membranes with an orange color can be due to a variety of etiologies. The conditions may appear as purely orange, yellow-orange, red-orange, tan, or brown with an orange hue. The orange color may also present as a transient phase of a disease process. As with all dermatologic pathology, a key way to distinguish orange-colored lesions is by distribution and morphology. The sclera, palate, lips, gingiva, and nails may also be involved. A literature review using PubMed with keywords, including orange, skin, mucosa, cutaneous, xanthoderma, and granuloma, was conducted to gather all dermatologic conditions that can present with an orange color. The relevant diseases were categorized by etiology and include inflammatory, infectious, neoplastic, and exogenous causes.

Mesenchymal Stromal Cells Isolated from Irradiated Human Skin Have Diminished Capacity for Proliferation, Differentiation, Colony Formation, and Paracrine Stimulation.

Ionizing radiation, commonly used in the treatment of solid tumors, has unintended but deleterious effects on overlying skin and is associated with chronic nonhealing wounds. Skin-derived mesenchymal stromal cells (SMSCs) are a pluripotent population of cells that are critically involved in skin homeostasis and wound healing. The aim of this study was to isolate and functionally characterize SMSCs from human skin that was previously irradiated as part of neoadjuvant or adjuvant cancer therapy. To this end, SMSCs were isolated from paired irradiated and nonirradiated human skin samples. Irradiated SMSCs expressed characteristic SMSC markers at lower levels, had disorganized cytoskeletal structure, and had disordered morphology. Functionally, these cells had diminished proliferative capacity and substantial defects in colony-forming capacity and differentiation in vitro. These changes were associated with significant differential expression of genes known to be involved in skin physiology and wound healing. Conditioned media obtained from irradiated SMSCs affected fibroblast but not endothelial cell proliferation and migration. These results suggest that in situ damage to SMSCs during neoadjuvant or adjuvant radiation may play a critical role in the pathogenesis of slow or nonhealing radiation wounds. Stem Cells Translational Medicine 2019;8:925&934.

Safety and efficacy of placing internal jugular dialysis catheter tip in the inferior vena cava.

PURPOSE: To assess the efficacy and safety of placing the tip of the internal jugular (IJ) hemodialysis catheter in the inferior vena cava (IVC) in situations where it does not work well when placed in the right atrium. METHODS: The medical records of chronic hemodialysis patients at an outpatient vascular intervention facility were retrospectively reviewed. Out of the 831 patients who had dialysis catheters exchanged over a 4-year period, 13 patients were identified who underwent catheter exchanges where the tip of the catheter was placed in the IVC via the IJ approach. These were all patients where the catheters had poor flows when placed in the right atrium earlier. RESULTS: Adequate flow (>350 mL/min) was achieved in all 13 cases with the catheter placed in the IVC with no significant complications. CONCLUSIONS: This study suggests that exchanging the catheter and placing the tip in the IVC is effective and safe in certain situations especially when the tip placement in the conventional position (i.e. the right atrium) does not work well.

Retrograde dissection of the axillary artery during arteriogram via arteriovenous access.

INTRODUCTION: Retrograde arterial dissection is a recognized complication of endovascular intervention but has not been well reported especially in the context of dialysis arteriovenous access procedures. The management of this complication is also not well defined. CASE PRESENTATION: We report the case of an 80-year-old female with end-stage renal disease (ESRD) on dialysis who developed an asymptomatic retrograde dissection of the left axillary artery during an arteriogram performed via a retrograde approach as part of access dysfunction evaluation. The condition was managed conservatively with no other intervention and close follow-up. No surgical intervention or stenting was needed in this case. DISCUSSION: Conservative management of retrograde arterial dissection in the arm may be a viable option especially in asymptomatic patients due to the nature of the injury. The force of blood flow in the antegrade direction limits the expansion of the false lumen and likely promotes the spontaneous healing of the vessel.

Update and Review on the Surgical Management of Primary Cutaneous Melanoma.

The surgical management of malignant melanoma historically called for wide excision of skin and subcutaneous tissue for any given lesion, but has evolved to be rationally-based on pathological staging. Breslow and Clark independently described level and thickness as determinant in prognosis and margin of excision. The American Joint Committee of Cancer (AJCC) in 1988 combined features from each of these histologic classifications, generating a new system, which is continuously updated and improved. The National Comprehensive Cancer Network (NCCN) has also combined several large randomized prospective trials to generate current guidelines for melanoma excision as well. In this article, we reviewed: (1) Breslow and Clark classifications, AJCC and NCCN guidelines, the World Health Organization's 1988 study, and the Intergroup Melanoma Surgical Trial; (2) Experimental use of Mohs surgery for in situ melanoma; and (3) Surgical margins and utility and indications for sentinel lymph node biopsy (SLNB) and lymphadenectomy. Current guidelines for the surgical management of a primary melanoma of the skin is based on Breslow microstaging and call for cutaneous margins of resection of 0.5 cm for MIS, 1.0 cm for melanomas ≤1.0 mm thick, 1-2 cm for melanoma thickness of 1.01-2 mm, 2 cm margins for melanoma thickness of 2.01-4 mm, and 2 cm margins for melanomas >4 mm thick. Although the role of SLNB, CLND, and TLND continue to be studied, current recommendations include SLNB for Stage IB (includes T1b lesions ≤1.0 with the adverse features of ulceration or ≥1 mitoses/mm²) and Stage II melanomas. CLND is recommended when sentinel nodes contain metastatic deposits.