Large-scale functional inference for skin-expressing lncRNAs using expression and sequence information.

Long noncoding RNAs (lncRNAs) regulate the expression of protein-coding genes and have been shown to play important roles in inflammatory skin diseases. However, we still have limited understanding of the functional impact of lncRNAs in skin, partly due to their tissue specificity and lower expression levels compared with protein-coding genes. We compiled a comprehensive list of 18,517 lncRNAs from different sources and studied their expression profiles in 834 RNA-Seq samples from multiple inflammatory skin conditions and cytokine-stimulated keratinocytes. Applying a balanced random forest to predict involvement in biological functions, we achieved a median AUROC of 0.79 in 10-fold cross-validation, identifying significant DNA binding domains (DBDs) for 39 lncRNAs. G18244, a skin-expressing lncRNA predicted for IL-4/IL-13 signaling in keratinocytes, was highly correlated in expression with F13A1, a protein-coding gene involved in macrophage regulation, and we further identified a significant DBD in F13A1 for G18244. Reflecting clinical implications, AC090198.1 (predicted for IL-17 pathway) and AC005332.6 (predicted for IFN-γ pathway) had significant negative correlation with the SCORAD metric for atopic dermatitis. We also utilized single-cell RNA and spatial sequencing data to validate cell type specificity. Our research demonstrates lncRNAs have important immunological roles and can help prioritize their impact on inflammatory skin diseases.

A Rare Case of Hydrophilic Polymer Embolization After Transcatheter Aortic Valve Replacement.

ABSTRACT: Endovascular procedures that use a hydrophilic polymer-coated device carry a risk of embolization and ischemic complications when used intravascularly. Because these coatings are increasingly used worldwide, it is important to identify potential adverse effects early. Cutaneous complications of hydrophilic polymer emboli are rare and not commonly described in the literature. Therefore, we report a case of hydrophilic polymer embolization with cutaneous findings in a patient who underwent a recent transcatheter aortic valve replacement.

Skin-Expressing lncRNAs in Inflammatory Responses.

Long non-coding RNAs (lncRNAs) have attracted attention for their potential roles in modulating keratinocyte differentiation and inflammatory response; however, for many identified skin-expressing lncRNAs, there is no comprehensive characterization regarding their biological roles. In addition, the reported expression profiles for lncRNAs can be ambiguous due to their low-expressing nature. The objective of this review is to utilize large scale genomic data to characterize the prominent skin-expressing lncRNAs, aiming to provide additional insights for their potential roles in the pathology of inflammatory skin of psoriasis and atopic dermatitis by integrating in vitro and in vivo data. We highlighted the different skin-expressing lncRNAs, including H19, which is significantly down-regulated in lesional skin of AD/psoriasis and upon cytokine stimulation in keratinocytes; it is also negatively correlated with CYP1A1 (r = -0.75, p = 8 × 10-73), a gene involved in drug metabolism and skin barrier homeostasis, in keratinocytes. In addition, SPRR2C, a potential regulator that modulates IL-22 stimulation, was upregulated in both atopic dermatitis and psoriasis lesional skin and was also downstream of the IL-17A and IL-17 + TNF signaling in keratinocytes. Using scRNAseq, we further revealed the cell type specificity of lncRNAs, including basal-expressing nature of H19 in the epidermis. Interestingly, instead of having cell type specific expression profile, we found few lncRNAs that are express across different cell types in skin, including MALAT1, NEAT1, and GAS5. While lncRNAs in general have lower expression, our results combining in vitro and in vivo experimental data demonstrate how some of these lncRNAs can play mediator roles in the cytokine-stimulated pathway.

Patient- and Family-centered Rounding: A Single-site Look into the Room.

INTRODUCTION: The American Academy of Pediatrics recommends Patient- and Family-centered Rounds (PFCRs) to improve communication between the healthcare team and families while allowing the latter to participate in medical decision-making. PFCRs have a secondary goal of increasing rounds' efficiency and providing a positive learning environment for residents and students. There are many published best practices for PFCR. Our study provides an observational evaluation of PFCR in an academic tertiary medical center using a checklist created from such published best practices. METHODS: We created a standardized observation checklist based on published guidelines. Study members observed 200 individual rounding encounters using this instrument. All inpatient, nonsurgical rounding teams in the fall of 2014 were included and analyzed using descriptive statistics. RESULTS: The average rounding encounter included 9 team members, lasted 9 minutes and 24 seconds, with the medical team entering the patient room for 80.0% of encounters. Families were invited to participate in 60% of the encounters. Lay language was utilized in 62% of the encounters, although 99.5% of the encounters staff used medical terminology. Nursing was present in 64.5% of encounters but presented in only 13.5% of those encounters. The teaching-attending modeled patient interaction behaviors such as eye contact, nodding, and leaning forward in 31%-51% of encounters. CONCLUSIONS: Despite published best practices, medical teams at a large tertiary care center did not adhere to many components of published PCFR guidelines. Future studies should focus on family and physician experience to identify improvement strategies for rounds.

Progression of acute-to-chronic atopic dermatitis is associated with quantitative rather than qualitative changes in cytokine responses.

BACKGROUND: Although multiple studies have assessed molecular changes in chronic atopic dermatitis (AD) lesions, little is known about the transition from acute to chronic disease stages, and the factors and mechanisms that shape chronic inflammatory activity. OBJECTIVES: We sought to assess the global transcriptome changes that characterize the progression from acute to chronic stages of AD. METHODS: We analyzed transcriptome changes in paired nonlesional skin, acute and chronic AD lesions from 11 patients and 38 healthy controls by RNA-sequencing, and conducted in vivo and histological assays to evaluate findings. RESULTS: Our data demonstrate that approximately 74% of the genes dysregulated in acute lesions remain or are further dysregulated in chronic lesions, whereas only 34% of the genes dysregulated in chronic lesions are altered already in the acute stage. Nonlesional AD skin exhibited enrichment of TNF, TH1, TH2, and TH17 response genes. Acute lesions showed marked dendritic-cell signatures and a prominent enrichment of TH1, TH2, and TH17 responses, along with increased IL-36 and thymic stromal lymphopoietin expression, which were further heightened in chronic lesions. In addition, genes involved in skin barrier repair, keratinocyte proliferation, wound healing, and negative regulation of T-cell activation showed a significant dysregulation in the chronic versus acute comparison. Furthermore, our data show progressive changes in vasculature and maturation of dendritic-cell subsets with chronicity, with FOXK1 acting as immune regulator. CONCLUSIONS: Our results show that the changes accompanying the transition from nonlesional to acute to chronic inflammation in AD are quantitative rather than qualitative, with chronic AD having heightened TH2, TH1, TH17, and IL36 responses and skin barrier repair mechanisms. These findings provide novel insights and highlight underappreciated pathways in AD pathogenesis that may be amenable to therapeutic targeting.

Taking the Pain out of Somatization: Development and Implementation of a Hospital-Based Clinical Practice Guideline to Address Pediatric Somatic Symptom and Related Disorders.

OBJECTIVES: The diagnostic category of somatic symptom and related disorders (SSRDs), although common, is often poorly recognized and suboptimally managed in inpatient pediatric care. Little literature exists to address SSRDs in the inpatient pediatric setting. The purpose of the study was to characterize current SSRD practice, identify problem areas in workflow, and develop a standardized approach to inpatient evaluation and management at a tertiary care academic children's hospital. METHODS: A multidisciplinary group identified patients with SSRD admitted between May 2012 and October 2014. A retrospective chart review on a convenience sample was performed to identify population characteristics and current practice. Lean methodology was used to define current state practice and future state intervention. These methods were used to guide identification of problem areas, which informed protocol, a clinical practice guideline, and resource development. RESULTS: Thirty-six patients aged 8 to 17 years met inclusion criteria for chart review. Most patients presented with either neurologic or pain-related complaints. The mean length of stay was 5.44 days (SD = 6.3), with few patients receiving a mental health consultation within 24 hours of hospitalization. Patients averaged 5.8 medical and/or psychiatric diagnoses on discharge (SD = 5.2), and two-thirds did not have an SSRD diagnosis. Half of patients had comorbid psychiatric diagnoses, whereas one-quarter were discharged with no mental health follow-up. CONCLUSIONS: In this study, we describe the process and content development of a single-site institutional protocol, clinical practice guideline, and resources for the evaluation and management of pediatric SSRDs. This study may serve as a model for similar standardization of SSRD care in other inpatient pediatric medical settings.

Firearms Screening in the Pediatric Inpatient Setting.

OBJECTIVES: Firearm-related deaths remain a top cause of mortality in American children and adolescents. In a 2012 policy statement, the American Academy of Pediatrics urged pediatricians to incorporate questions about the availability of firearms into their patient history taking. We aim to evaluate the frequency of screening for home firearms in an academic tertiary-care hospital inpatient setting. METHODS: This retrospective chart review examined patients with the following pediatric diagnoses admitted to a tertiary-care pediatric hospital from 2006 to 2015: asthma, bronchiolitis, cellulitis, jaundice, single liveborn infant, bacterial and viral pneumonia, and all mood disorders. Data analysts then searched the patient charts that met these inclusion criteria for documentation of firearm screening as indicated by use of the terms "firearm," "pistol," "gun," "handgun," "bullet," "ammunition," or "rifle" in the admissions history and physical. RESULTS: Evidence of screening for firearms in the home was found in 1196 of the 40 658 charts included in the study (2.94%). The most frequently screened diagnosis and admitting service were mood disorders and child psychiatry, respectively (1159 of 3107; 37.3%). Only 19.8% of identified gun-owning families received specific anticipatory guidance. CONCLUSIONS: Firearm screening and gun safety education occurred infrequently in the inpatient setting. Inpatient encounters may provide an opportunity for increased screening and education because the hospital environment also includes additional resources, exposure to a greater number of providers, and the presence of more family members or caregivers. Further studies are warranted to explore barriers to inpatient screening and possible mechanisms for improvement.