Baby Wet Wipes: An Unusual Culprit of Lymphomatoid Contact Dermatitis Mimicking Mycosis Fungoides.

ABSTRACT: Lymphomatoid contact dermatitis (LCD) is a rare, benign pseudolymphoma with clinicopathologic features of both allergic contact dermatitis and cutaneous T-cell lymphoma (CTCL). In this article, we report a fascinating case of LCD secondary to chronic baby wet wipe use with clinical features of allergic contact dermatitis and histopathologic changes of mycosis fungoides, a subtype of CTCL. We argue that LCD should be added to the list of mimickers of mycosis fungoides, a subtype of CTCL.

Synthesis and Characterization of 2-Decenoic Acid Modified Chitosan for Infection Prevention and Tissue Engineering.

Chitosan nanofiber membranes are recognized as functional antimicrobial materials, as they can effectively provide a barrier that guides tissue growth and supports healing. Methods to stabilize nanofibers in aqueous solutions include acylation with fatty acids. Modification with fatty acids that also have antimicrobial and biofilm-resistant properties may be particularly beneficial in tissue regeneration applications. This study investigated the ability to customize the fatty acid attachment by acyl chlorides to include antimicrobial 2-decenoic acid. Synthesis of 2-decenoyl chloride was followed by acylation of electrospun chitosan membranes in pyridine. Physicochemical properties were characterized through scanning electron microscopy, FTIR, contact angle, and thermogravimetric analysis. The ability of membranes to resist biofilm formation by S. aureus and P. aeruginosa was evaluated by direct inoculation. Cytocompatibility was evaluated by adding membranes to cultures of NIH3T3 fibroblast cells. Acylation with chlorides stabilized nanofibers in aqueous media without significant swelling of fibers and increased hydrophobicity of the membranes. Acyl-modified membranes reduced both S. aureus and P.aeruginosa bacterial biofilm formation on membrane while also supporting fibroblast growth. Acylated chitosan membranes may be useful as wound dressings, guided regeneration scaffolds, local drug delivery, or filtration.

INteractive Virtual Expert-Led Skills Training: A Multi-Modal Curriculum for Medical Trainees.

Background: Internationally, pediatric depression and suicide are significant issues. Additionally, in the context of the COVID-19 pandemic, pediatric mental health needs are rising astronomically. In light of Child & Adolescent Psychiatrist (CAP) subspecialist shortages in the United States (US), there is an increasing call for primary care physicians in Family Medicine and Pediatrics to address an increasingly broad variety of patient needs. Here we report on the development and preliminary evaluation of medical student and resident perceptions on the "INteractive Virtual Expert-led Skills Training" (INVEST) medical education curriculum, a virtual synchronous CAP curriculum employing active learning strategies, including expert-led discussion and video modeling, and discussion designed to meet those priorities. Methods: In a standardized 60-min training format, our curriculum leverages audience response system polling, video modeling of key clinical skills, and interactive discussion with an expert subspecialist, over a virtual video conferencing platform. The primary educational strategy relies on use of video modeling to demonstrate best practice with CAP led group discussion to solidify and explain important concepts. Five waves of medical students and residents (N = 149) participated in the INVEST curriculum and completed pre- and post-training surveys regarding knowledge and comfort in the management of pediatric patients with depression and suicidality. Results: Trainee participants reported significant positive gains in perceived likelihood of encountering pediatric suicidality as well as knowledge/comfort with depression screening and suicidality assessment in a primary care setting. Across some competency areas, there was an effect of medical learner level. Learners at lower levels generally reported the highest benefit. Medical students reported significant increases in their comfort interpreting and discussing positive depression screens and evidenced the greatest relative benefit in comfort with discussing suicidality. Conclusion: To our knowledge, INVEST is the first fully virtual, multimodal curriculum led by expert CAP subspecialists. Our findings suggest that INVEST shows promise for equipping medical learners with baseline knowledge for caring for patients with pediatric depression and suicidality. This synchronous, virtually delivered curriculum allows for critical training delivered to diverse medical learners regardless of geographic location, a particular benefit during the current COVID-19 pandemic.

Long-Term Controlled Release of Simvastatin from Photoprinted Triple-Networked Hydrogels Composed of Modified Chitosan and PLA-PEG Micelles.

Local delivery of active agents using injectable or implantable hydrogels for tissue and bone regeneration is a promising therapy, but it remains challenging for controlling dose and duration of release. Simvastatin (SMV), a hydrophobic drug, has shown potential for osteogenic stimulation. Secure loading of hydrophobic drugs by physical interactions is particularly difficult to establish in hydrophilic polymer matrices, and their sustained release over several months for long-term regeneration has rarely been reported. Additionally, mechanical properties of hydrogels must be improved for a sufficient support while maintaining eventual biodegradability. This study assesses the effect of controlled SMV release from 3D-printed triple-network hydrogels for osteogenic stimulation and characterizes their mechanical and biological properties as an implant. SMV is loaded into polymeric micelles of polylactide/poly(ethylene glycol) triblock copolymers (PLA-PEG-PLA) and mixed with N-methacryloyl chitosan and PEG dimethacrylate to fabricate hydrogels by photo-cross-linked 3D printing. The hydrogel properties and drug release profiles have shown significant dependance on the polymer compositions. The SMV release from the triple-polymer-network hydrogel has continued for 17 weeks of observation. Cytocompatibility of hydrogels with various formulations is confirmed. The tunable triple-network hydrogels loaded with SMV provide a potential therapeutic value for bone regeneration.

Potentially life­threatening severe cutaneous adverse reactions associated with tyrosine kinase inhibitors (Review).

Tyrosine kinase inhibitors (TKIs) have emerged as a new frontier of cancer therapy. These agents include inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), BRAF, mitogen­activated protein kinase kinase (also referred to as MEK), bcr­abl, c­KIT, platelet­derived growth factor (PDGFR), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK) and vascular endothelial growth factor (VEGF). Along with the evolving applications of TKIs, there has been an increased recognition of the breadth of potential cutaneous toxicities to these agents. In this review, we provide an overview of potentially life­threatening severe cutaneous adverse reactions (SCARs) that may occur during therapy with TKIs. These toxicities include Stevens­Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

Generation and basic characterization of a gene-trap knockout mouse model of Scn2a with a substantial reduction of voltage-gated sodium channel Nav 1.2 expression.

Large-scale genetic studies revealed SCN2A as one of the most frequently mutated genes in patients with neurodevelopmental disorders. SCN2A encodes for the voltage-gated sodium channel isoform 1.2 (Nav 1.2) expressed in the neurons of the central nervous system. Homozygous knockout (null) of Scn2a in mice is perinatal lethal, whereas heterozygous knockout of Scn2a (Scn2a+/- ) results in mild behavior abnormalities. The Nav 1.2 expression level in Scn2a+/- mice is reported to be around 50-60% of the wild-type (WT) level, which indicates that a close to 50% reduction of Nav 1.2 expression may not be sufficient to lead to major behavioral phenotypes in mice. To overcome this barrier, we characterized a novel mouse model of severe Scn2a deficiency using a targeted gene-trap knockout (gtKO) strategy. This approach produces viable homozygous mice (Scn2agtKO/gtKO ) that can survive to adulthood, with about a quarter of Nav 1.2 expression compared to WT mice. Innate behaviors like nesting and mating were profoundly disrupted in Scn2agtKO/gtKO mice. Notably, Scn2agtKO/gtKO mice have a significantly decreased center duration compared to WT in the open field test, suggesting anxiety-like behaviors in a novel, open space. These mice also have decreased thermal and cold tolerance. Additionally, Scn2agtKO/gtKO mice have increased fix-pattern exploration in the novel object exploration test and a slight increase in grooming, indicating a detectable level of repetitive behaviors. They bury little to no marbles and have decreased interaction with novel objects. These Scn2a gene-trap knockout mice thus provide a unique model to study pathophysiology associated with severe Scn2a deficiency.

The life-threatening eruptions of immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICPi) have emerged as a new frontier of cancer therapy. Although monoclonal antibodies to cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have revolutionized oncologic management, these agents may result in a spectrum of immune-related adverse events (irAE) of which dermatologic toxicities are among the most frequent. Prompt recognition and management of irAE is essential for dermatologists caring for the expanding population of cancer patients exposed to these drugs. Cutaneous toxicities range from mild cases to severe and life-threatening presentations that may cause significant morbidity and mortality. This review provides an overview of severe cutaneous adverse reactions (SCARs) that may develop during ICPi therapy, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, immunobullous disorders, erythroderma, neutrophilic dermatoses, and cutaneous eruptions associated with systemic manifestations are discussed.

Lobular neutrophilic panniculitis associated with DNA methyltransferase inhibitors in the treatment of myeloid disease.

Cutaneous toxicities to DNA methyltransferase inhibitors are variable and include localized injection site reactions, ecchymoses, maculopapular eruptions, and neutrophilic dermatoses including pyoderma gangrenosum, Sweet syndrome, and neutrophilic eccrine hidradenitis. This series describes two patients diagnosed with lobular neutrophilic panniculitis arising during treatment of acute myelogenous leukemia with "hypomethylating drugs," including the first report of its occurrence with a next-generation agent. Differential diagnoses, histopathologic characteristics, treatment considerations, and proposed pathogenesis will be discussed.

Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management.

BACKGROUND: There is increasing recognition of distinct inflammatory eruptions associated with checkpoint inhibitors. A better understanding of their severity, therapeutic response, and impact on cancer treatment is needed. OBJECTIVE: To analyze the different rashes associated with immunotherapy referred to our institution's oncodermatology clinic and inpatient consultative service and to evaluate their therapeutic response and impact on immunotherapy. METHODS: We retrospectively reviewed the medical records of patients referred to the oncodermatology clinic or inpatient dermatology service during 2016-2018 at Yale-New Haven Hospital for eruptions that developed during immunotherapy. RESULTS: In total, 98 patients (51 men, 47 women) treated with checkpoint inhibitors developed 103 inflammatory eruptions, with a range of mean latency of 0.2-17.7 months. A minority of patients (25/103; 24.3%) required immunotherapy interruption; most of these cases involved immunobullous (7/8; 87.5%), lichenoid (8/26; 30.8%), maculopapular (6/18; 33.3%), and Stevens-Johnson syndrome-like (2/2, 100%) reactions. Only 3 of 16 (18.8%) patients who had their immunotherapy interrupted had a grade 2 or 3 flare on rechallenge. Most reactions (93/103; 90.3%) responded to dermatologic therapy or immunotherapy interruption. LIMITATIONS: This was a retrospective study from a single tertiary care center. CONCLUSION: A variety of inflammatory reactions might occur from immunotherapy with differing degrees of severity. While most rashes responded to topical treatment, immunobullous and exfoliative presentations frequently interrupted immunotherapy. Increased awareness and early recognition could reduce the need for unnecessary immunotherapy interruption.

Impact of a clinical interventions bundle on uptake of HPV vaccine at an OB/GYN clinic.

INTRODUCTION: HPV vaccine uptake is lowest among young adults. Little is known about the most effective way to decrease missed opportunities (MO) and increase uptake of the vaccine in this vulnerable population. OBJECTIVES: To determine the impact of a clinical intervention bundle on the rate of MO and uptake of the vaccine among young adult women. METHODS: From 2/2014 to 7/2015, an intervention bundle (designating physician and nurse champions, pre-screening patients' charts, empowering nurses to recommend immunization, providing no-cost vaccinations, placing prompts in clinic note templates, eliminating requirement for pre-vaccination pregnancy test) was implemented at an urban, hospital-based OB/GYN clinic. Medical records were reviewed for all vaccine-eligible (non-pregnant, 11-26 years) women seen between 2/2013 and 9/2016. Impact of the bundled interventions on the monthly rates of MO and vaccine uptake was estimated by analyzing immunization trends with an interrupted time-series model using counterfactual comparison groups in order to control for pre-existing trends. RESULTS: There were 6,463 vaccine-eligible visits during our study period. The prevalence of women who had both completed and initiated the series was significantly higher, 20.3% and 29.7% respectively, in the last month, compared to their counterfactuals (p < 0.01). In the last study month, the rate of MO was significantly lower than its counterfactual (19.73 per 100 encounters lower, p < 0.01). Hispanic women had attributable reductions in their rates of MO that were twice that of White women. Statistically significant attributable reductions were also seen among Spanish speakers, publicly insured, and uninsured women. CONCLUSIONS: Implementation of this intervention bundle effectively reduced the monthly rate of MO and increased the prevalence of women who had initiated and completed the HPV vaccine series. The reduction of MO was most drastic among Hispanic, publicly insured and uninsured women compared to White and privately insured.

Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and peripheral blood mononuclear cells.

Triggers of the autoimmune response that leads to type 1 diabetes (T1D) remain poorly understood. A possibility is that parallel changes in both T cells and target cells provoke autoimmune attack. We previously documented greater Ca2+ transients in fibroblasts from T1D subjects than non-T1D after exposure to fatty acids (FA) and tumor necrosis factor α (TNFα). These data indicate that metabolic and signal transduction defects present in T1D can be elicited ex vivo in isolated cells. Changes that precede T1D, including inflammation, may activate atypical responses in people that are genetically predisposed to T1D. To identify such cellular differences in T1D, we quantified a panel of metabolic responses in fibroblasts and peripheral blood cells (PBMCs) from age-matched T1D and non-T1D subjects, as models for non-immune and immune cells, respectively. Fibroblasts from T1D subjects accumulated more lipid, had higher LC-CoA levels and converted more FA to CO2, with less mitochondrial proton leak in response to oleate alone or with TNFα, using the latter as a model of inflammation. T1D-PBMCs contained and also accumulated more lipid following FA exposure. In addition, they formed more peroxidized lipid than controls following FA exposure. We conclude that both immune and non-immune cells in T1D subjects differ from controls in terms of responses to FA and TNFα. Our results suggest a differential sensitivity to inflammatory insults and FA that may precede and contribute to T1D by priming both immune cells and their targets for autoimmune reactions.

Nonuse of bicycle helmets and risk of fatal head injury: a proportional mortality, case-control study.

BACKGROUND: The effectiveness of helmets at preventing cycling fatalities, a leading cause of death among young adults worldwide, is controversial, and safety regulations for cycling vary by jurisdiction. We sought to determine whether nonuse of helmets is associated with an increased risk of fatal head injury. METHODS: We used a case-control design involving 129 fatalities using data from a coroner's review of cycling deaths in Ontario, Canada, between 2006 and 2010. We defined cases as cyclists who died as a result of head injuries; we defined controls as cyclists who died as a result of other injuries. The exposure variable was nonuse of a bicycle helmet. RESULTS: Not wearing a helmet while cycling was associated with an increased risk of dying as a result of sustaining a head injury (adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 1.3-7.3). We saw the same relationship when we excluded people younger than 18 years from the analysis (adjusted OR 3.5, 95% CI 1.4-8.5) and when we used a more stringent case definition (i.e., only a head injury with no other substantial injuries; adjusted OR 3.6, 95% CI 1.2-10.2). INTERPRETATION: Not wearing a helmet while cycling is associated with an increased risk of sustaining a fatal head injury. Policy changes and educational programs that increase the use of helmets while cycling may prevent deaths.