Insights into Lichen Planus Pigmentosus Inversus using Minimally Invasive Dermal Patch and Whole Transcriptome Analysis.

Lichen Planus Pigmentosus inversus (LPPi) is a rare interface and lichenoid dermatitis (ILD) and supposed variant of lichen planus (LP) that presents as well-demarcated brown to grey macules in flexural and intertriginous areas. LPPi is deemed 'inversus' because its anatomical distribution in skin folds is opposite that seen in lichen planus pigmentosus (LPP) whose pigmented lesions arise on sun-exposed skin. Biopsy is required for the clinical diagnosis of all ILDs. Though multiple clinically-oriented studies have reported differences between LPP, LPPi, and LP, few molecular studies have been performed. In this case study, 3 patients, 2 with LPPi and one with LP, provided samples using minimally invasive whole transcriptome analysis using a dermal biomarker patch. This study confirms the involvement of interferon signaling and T-cell activation in LPPi and suggests an expression profile distinct from LP. Specific genes significantly upregulated in LPPi vs LP include an intergenic splice variant of the primary pigmentation determining receptor in humans and dysregulation of genes essential for ceramide synthesis and construction of the cornified envelope. This work expands upon our knowledge of the pathogenesis of LPPi vs LP, and supports the potential use of this technology in the diagnostic clinical setting to mitigate the need for invasive procedures.

Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia.

BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.

Traumatic Anterior L4 Fracture Dislocation With Iliac Artery Compression in a 6-Year-Old Patient: A Case Report.

CASE: A six-year-old Caucasian boy sustained an L4 anterior fracture dislocation with cauda equina transection at L3/L4 level with L4 vertebral body compression of the left common iliac artery after a single motor vehicle accident. He was treated with emergent open reduction and pedicle screw fixation with return of left common iliac patency. This was followed by multiple bowel resections on postadmission day 3. CONCLUSION: Anterior spinal fracture dislocations in pediatric patients are rare, caused by high-energy collisions, and are often complicated by multiple traumatic injuries, including vascular and neurological compromise that necessitate emergent intervention.

Spironolactone and XPB: An Old Drug with a New Molecular Target.

Spironolactone (SP) is commonly used for the treatment of heart failure, hypertension, and complications of cirrhosis by antagonizing the mineralocorticoid receptor. However, SP also antagonizes the androgen receptor, and thus SP has also been shown to be effective in the treatment of acne, hair loss, and hirsutism in women. Interestingly, recent drug repurposing screens have identified new and diverse functions for SP as a simulator of tumor immunosurveillance and as an inhibitor of DNA repair and viral infection. These novel pharmacological effects of SP have all been linked to the ability of SP to induce the rapid proteolytic degradation of the xeroderma pigmentosum group B (XPB) protein. XPB is a critical enzymatic component of the multi-subunit complex known as transcription factor II-H (TFIIH), which plays essential roles in both DNA repair and the initiation of transcription. Given the critical functions for XPB and TFIIH in these processes, the loss of XPB by SP could lead to mutagenesis. However, the ability of SP to promote cancer stem cell death and facilitate immune recognition may counteract the negative consequences of SP to mitigate carcinogenic risk. Thus, SP appears to have new and interesting pharmacological effects that may extend its potential uses.

Implementation and case-study results of potentially better practices for family-centered care: the family-centered care map.

OBJECTIVE: The objective of this study was to enhance the ability to coordinate and deliver care in a holistic manner, through a family-centered care map, so that the developmental, physical, and psychosocial needs of the infant and family are met. METHODS: A Web-based map was based on 7 distinct clinical phases with 3 variations of an infant's course through a NICU. Sixty-three potentially better practices were identified and 7 potentially better practices were implemented through case studies. RESULTS: Measures of family satisfaction revealed improvements in delivery of family-centered care. Increases in discharge growth parameters for extremely low birth weight infants were demonstrated. Length of stay for very low birth weight infants decreased from 73 to 60 days in Vermont. CONCLUSIONS: The collaborative process enhances identification of potentially better practices and results in both qualitative and quantitative improvements in family-centered care.

Development and dissemination of potentially better practices for the provision of family-centered care in neonatology: the family-centered care map.

OBJECTIVE: Family-centered care has become integral to the provision of quality neonatal intensive care. However, practices that reflect the core principles of family-centered care have not been described fully in the literature or implemented and evaluated consistently within newborn intensive care. The objective of this study was to create a family-centered care map that enhances the ability of the health care team to work with families to coordinate and deliver care in a holistic manner to meet the developmental, physical, and psychosocial needs of NICU patients and their families. METHODS: Potentially better practices were developed for sequential clinical phases by using standardized methods. These included focus groups with families, brainstorming sessions with staff, literature review, and input from established family advisory groups and family-centered care experts. Potentially better practices then were integrated into the family-centered care map that was configured in a Web-based format. Overall utility will be evaluated by determining the effect of the family-centered care map on length of stay, parental satisfaction, and family-centered care beliefs and practices among NICU staff. RESULTS: Sixty-three potentially better practices were identified for 7 clinical phases and 3 variations that were believed to characterize the clinical course of a typical NICU patient. A prototype of the Web-based family-centered care map that illustrates the clinical phases with links to the related potentially better practices, operational processes, and case studies was created. Baseline data from a care provider survey, from a family satisfaction survey, and on length of stay have been collected. CONCLUSIONS: Quality improvement methods and collaboration among 3 centers led to the development of an innovative Web-based resource to assist individual care providers and family advisors to provide comprehensive family-centered care to infants and families. Implementation of the family-centered care map has potential to affect positively the quality of newborn intensive care and lead to improved long-term outcomes.