The Safety of Isotretinoin Treatment in Patients with Peanut Allergies.

Background: Isotretinoin, the gold standard treatment for nodulocystic acne vulgaris, is contraindicated in patients with a soy allergy. Due to potential cross-reactivity, a history of peanut allergy is listed as a contraindication to isotretinoin use in some countries. Objective: We sought to further evaluate the safety of isotretinoin use in patients with peanut allergy. Methods: Using Epic's SlicerDicer, patients were identified with both an allergy to peanuts and history of isotretinoin use for treatment of acne vulgaris. Clinical manifestation to peanut exposure, peanut-specific skin prick and/or IgE testing, and adverse reactions to isotretinoin use were recorded via chart review and phone interviews. Results: Ten patients were identified having both a peanut allergy and treatment for acne vulgaris with isotretinoin. All patients tolerated isotretinoin without evidence of allergy. Conclusion: Isotretinoin use did not result in allergic eruptions in patients with a known peanut allergy, however, more robust clinical studies are needed to confirm the extent of its use in this patient population.

The positive environmental impact of virtual isotretinoin management.

BACKGROUND/OBJECTIVES: Other medical specialties have studied how their practices influence the environment, but environmental impact studies in the field of dermatology remain limited. With respect to dermatology, vehicle emissions by patients traveling to and from appointments are an important factor influencing climate change. This study was undertaken to determine the greenhouse gas emissions avoided by managing isotretinoin virtually at West Virginia University Hospital. METHODS: A retrospective cross-sectional study was conducted during the COVID-19 outbreak from March 25 to December 1, 2020, where travel data were acquired and converted to emission data. RESULTS: 5,137 kg of GHG emissions in CO2 equivalents were prevented by managing isotretinoin virtually during the study period. 49 400 kg of GHG emissions in CO2 equivalents would be prevented annually. This is the emission load released when 24 690 kg of coal are burned. CONCLUSIONS: Environmental impact studies in the field of dermatology remain limited. GHG emissions were significantly reduced by virtually managing isotretinoin at a single institution. The practice of dermatology could reduce its carbon footprint by managing isotretinoin virtually, even in non-pandemic periods. Given that isotretinoin management represents a small percentage of the overall carbon footprint associated with dermatology, dermatologists should identify other conditions amenable to virtual medicine to produce greater environmental impact.

Validation of CP-GEP (Merlin Assay) for predicting sentinel lymph node metastasis in primary cutaneous melanoma patients: A U.S. cohort study.

BACKGROUND: Approximately 85% of melanoma patients who undergo a sentinel lymph node biopsy (SLNB) are node-negative. Melanoma incidence is highest in patients ≥65 years, but their SLNB positivity rate is lower than in younger patients. CP-GEP, a model combining clinicopathologic and gene expression variables, identifies primary cutaneous melanoma (CM) patients who may safely forgo SLNB due to their low risk for nodal metastasis. Here, we validate CP-GEP in a U.S. melanoma patient cohort. METHODS: A cohort of 208 adult patients with primary CM from the Mayo Clinic and West Virginia University was used. Patients were stratified according to their risk for nodal metastasis: CP-GEP High Risk and CP-GEP Low Risk. The main performance measures were SLNB reduction rate (RR) and negative predictive value (NPV). RESULTS: SLNB positivity rate for the entire cohort was 21%. Most patients had a T1b (34%) or T2a (31%) melanoma. In the T1-T2 group (153 patients), CP-GEP achieved an SLNB RR of 41.8% (95% CI: 33.9-50.1) at an NPV of 93.8% (95% CI: 84.8-98.3). Subgroup analysis showed similar performance in T1-T2 patients ≥65 years of age (51 patients; SLNB positivity rate, 9.8%): SLNB RR of 43.1% (95% CI: 29.3-57.8) at an NPV of 95.5% (95% CI: 77.2-99.9). CONCLUSION: We confirmed the potential of CP-GEP to reduce negative SLNB in all relevant age groups. Our findings are especially relevant to patients ≥65 years, where surgery is often elective. CP-GEP may guide SLNB decision-making in clinical practice.

Association Between Alopecia Areata and Natural Hair Color Among White Individuals.

IMPORTANCE: Alopecia areata (AA) is a complex immune-mediated disorder that causes nonscarring hair loss. Previous reports have documented preferential targeting of pigmented hair follicles with sparing of gray, nonpigmented hair follicles in alopecia lesions. Thus, immune targeting of melanogenesis-associated proteins in melanocytes and keratinocytes represents a potential mechanism for the inflammation that targets anagen hairs in alopecia areata. OBJECTIVE: To investigate the association of alopecia areata with hair color among White residents of the UK. DESIGN, SETTING, AND PARTICIPANTS: This matched, case-control study conducted in October 2020 used a large prospectively acquired cohort and included data that were collected from the UK Biobank, a large-scale prospective resource designed to study phenotypic and genotypic determinants in adults. A total of 502 510 UK Biobank participants were reviewed for inclusion. Among these individuals, 1673 cases of alopecia areata with reported hair color were captured and matched by age and sex to 6692 controls without alopecia areata using 1:4 matching. MAIN OUTCOMES AND MEASURES: Conditional logistic regression analysis was performed, in which the outcome variable was alopecia areata and the main predictor was natural hair color before graying. The variables considered included diabetes, hypothyroidism, hyperthyroidism, and vitiligo. RESULTS: Of 464 353 participants, 254 505 (54.8%) were women, and the mean (SD) age for those with alopecia areata was 46.9 (16.5) years. Alopecia areata was significantly more common in individuals with black (adjusted odds ratio [aOR], 2.97; 95% CI, 2.38-3.71) and dark brown hair (aOR, 1.26; 95% CI, 1.11-1.42) compared with light brown hair. In contrast, blond individuals exhibited significantly decreased alopecia areata compared with those with light brown hair (aOR, 0.69; 95% CI, 0.56-0.85). Red hair color was not significantly different from light brown hair. CONCLUSIONS AND RELEVANCE: The findings of this matched case-control study seem to indicate that alopecia areata is modulated by natural hair color, preferentially targeting darker hair. Our results support a previously proposed model of alopecia areata in which immunity is directed against melanogenesis-associated proteins in the anagen hair follicles. However, further study is needed to more precisely understand the immunopathogenic association between alopecia areata and hair color.

Localized Versus Generalized Granuloma Annulare: A Retrospective Review of 407 Patients.

BACKGROUND: Granuloma annulare has been linked to diabetes, dyslipidemia, thyroid disease, collagen vascular disease, malignancies, infectious hepatitis, and systemic infections. However, these associations have not been systematically investigated when categorized by its clinical variants. OBJECTIVE: To evaluate disease associations of localized and generalized granuloma annulare. METHODS: In total, 407 granuloma annulare patients from 1989 to 2019 were retrospectively reviewed, categorized by clinical variant (localized or generalized), age (pediatric or adult), and diagnostic method (clinical or histologic). Descriptive statistical analyses and multivariate logistic regression analysis were performed. Fisher's exact tests were conducted to produce unbiased probability values. RESULTS: Overall, 75.2% of the study sample was female, 47.2% had dyslipidemia, 24.8% were diabetic, and 24.6% had thyroid disease. Dyslipidemia (OR 2.15, CI 1.95-2.35, P < .001), diabetes (OR 1.16, CI 1.01-1.31, P = .041), and histologic diagnosis (OR 2.08, CI 1.21-3.52, P = .007) were associated with increased risk of GGA compared to LGA. When stratified by adult versus pediatric cases, dyslipidemia and diagnostic method remained significant, but diabetes did not. CONCLUSIONS: Evaluating granuloma annulare by its clinical variants may help to determine disease associations with each variant.

Evaluating the Exfoliation Efficiency of Quasi-2D Metal Diboride Nanosheets Using Hansen Solubility Parameters.

Non-van der Waals (non-vdW) solids are emerging sources of two-dimensional (2D) nanosheets that can be produced via liquid-phase exfoliation (LPE), and are beginning to expand our understanding of 2D and quasi-2D materials. Recently, nanosheets formed by LPE processing of bulk metal diborides, a diverse family of layered non-vdW ceramic materials, have been reported. However, detailed knowledge of the exfoliation efficiency of these nanomaterials is lacking, and is important for their effective solution-phase processing and for understanding their fundamental surface chemistry, since they have significant differences from more conventional nanosheets produced from layered vdW compounds. Here in this paper we use Hansen solubility theory to investigate nanosheets of the metal borides CrB2 and MgB2 derived from LPE. By preparing dispersions in 33 different solvents, we determine Hansen solubility parameters (δD, δP, δH) for both these metal diborides. We find that they exhibit notably higher δP and δH values compared to conventional vdW materials such as graphene and MoS2, likely as a result of the types of bonds broken in such materials from exfoliation which allows for more favorable interactions with more polar and hydrogen-bonding solvents. We apply the solubility parameters to identify cosolvent blends suitable for CrB2 and MgB2 that produce dispersions with concentrations that match or exceed those of the top-performing individual solvents for each material and that have markedly higher stability compared to the constituent solvents of the blends alone. This work provides insight into the exfoliation effectiveness of different solvents for preparation of nanosheets from metal diborides and non-vdW materials in general. Such knowledge will be crucial for developing liquid-phase exfoliation strategies for incorporating these materials in applications such as nanocomposites, inks, and coatings.

Exfoliation of boron carbide into ultrathin nanosheets.

Liquid phase exfoliation (LPE) is a method that can be used to produce bulk quantities of two-dimensional (2D) nanosheets from layered van der Waals (vdW) materials. In recent years, LPE has been applied to several non-vdW materials with anisotropic bonding to produce nanosheets and platelets, but it has not been demonstrated for materials with strong isotropic bonding. In this paper, we demonstrate the exfoliation of boron carbide (B4C), the third hardest known material, into ultrathin nanosheets. B4C has a structure consisting of strongly bonded boron icosahedra and carbon chains, but does not have anisotropic cleavage energies to suggest that it can be readily cleaved into nanosheets. B4C has been widely studied for its very high melting point, high mechanical strength, and chemical stability, as well as its zero- and one-dimensional nanostructured forms. Herein, ultrathin nanosheets are successfully prepared by sonication of B4C powder in organic solvents and are characterized by microscopy and spectroscopy. Density functional theory (DFT) simulations reveal that B4C can be cleaved along several different crystallographic planes with similar energetic favourability, facilititated by an unexpected mechanism of breaking boron icosahedra and forming new boron-rich cage structures at the surface. Atomic force microscopy (AFM) shows that the nanosheets produced by LPE are as thin as 5 nm, with an average thickness of 31.4 nm and average area of 16 000 nm2. Raman spectroscopy shows that many of the nanosheets exhibit additional carbon-rich peaks that change with laser irradiation, which are attributed to atomic rearrangements and amorphization at the nanosheet surfaces, consistent with the diverse cleavage planes. High-resolution transmission electron microscopy (HRTEM) demonstrates that many different cleavage planes exist among the exfoliated nanosheets, in agreement with DFT simulations. This work elucidates the exfoliation mechanism of 2D B4C and suggests that LPE can be applied to generate nanosheets from a variety of non-layered and non-vdW materials.

Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors or methotrexate: A multicenter research network study.

BACKGROUND: Data on the impact of biologics and immunomodulators on coronavirus disease 2019 (COVID-19)-related outcomes remain scarce. OBJECTIVE: We sought to determine whether patients taking tumor necrosis factor inhibitors (TNFis) or methotrexate are at increased risk of COVID-19-related outcomes. METHODS: In this large comparative cohort study, real-time searches and analyses were performed on adult patients who were diagnosed with COVID-19 and were treated with TNFis or methotrexate compared with those who were not treated. The likelihood of hospitalization and mortality were compared between groups with and without propensity score matching for confounding factors. RESULTS: More than 53 million (53,511,836) unique patient records were analyzed, of which 32,076 (0.06%) had a COVID-19-related diagnosis documented starting after January 20, 2020. Two hundred fourteen patients with COVID-19 were identified with recent TNFi or methotrexate exposure compared with 31,862 patients with COVID-19 without TNFi or methotrexate exposure. After propensity matching, the likelihood of hospitalization and mortality were not significantly different between the treatment and nontreatment groups (risk ratio = 0.91 [95% confidence interval, 0.68-1.22], P = .5260 and risk ratio = 0.87 [95% confidence interval, 0.42-1.78], P = .6958, respectively). LIMITATIONS: All TNFis may not behave similarly. CONCLUSION: Our study suggests that patients with recent TNFi or methotrexate exposure do not have increased hospitalization or mortality compared with patients with COVID-19 without recent TNFi or methotrexate exposure.

Association between psoriasis, psoriatic arthritis and gastrointestinal disease : An exploratory nationwide inpatient sample analysis.

BACKGROUND: Psoriasis is associated with cardiovascular disease, inflammatory bowel disease (IBD), metabolic syndrome, and psychiatric disease. Furthermore, psoriasis is associated with immune dysregulation and systemic inflammation. OBJECTIVE: To determine the association of psoriasis and psoriatic arthritis with IBD and the association of the combination of psoriasis or psoriatic arthritis with IBD and other gastrointestinal illnesses. METHODS: Discharge data from the 2000-2014 Nationwide Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), which approximates a 20% stratified sample of all US hospitalizations, were analyzed. Multivariable logistic regression was used to examine the association between psoriasis and psoriatic arthritis with IBD and 23 gastrointestinal illnesses adjusting for sociodemographic characteristics. RESULTS: Psoriasis was associated with IBD (Crohn's disease adjusted odds ratio (aOR) = 2.13, 95% confidence interval (CI) [2.0-2.3], p < 0.001). When adjusting for sociodemographics and IBD, psoriasis was associated with 21 of 23 gastrointestinal diseases examined, most notably celiac disease, autoimmune hepatitis, and non-alcoholic fatty liver disease. Psoriatic arthritis was also associated with IBD (Crohn's disease, aOR = 1.95, 95% CI [1.7-2.2], and ulcerative colitis, aOR = 2.66, 95% CI [2.4-2.9]). CONCLUSION: Psoriasis and psoriatic arthritis inpatients have an associated increase in IBD and numerous other gastrointestinal illnesses.

The effect of a low-nickel diet and nickel sensitization on gastroesophageal reflux disease: A pilot study.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is a common medical condition, frequently refractory to medical therapy. Nickel is a leading cause of allergic contact dermatitis. Although nickel is widely found in foods, the effect of nickel on GERD is unknown. This pilot study sought to evaluate the effect of a low-nickel diet on GERD and determine if epicutaneous patch testing to nickel could predict responsiveness to a low-nickel diet. METHODS: This prospective, single-site pilot study recruited 20 refractory GERD patients as determined by GERD Health-Related Quality of Life (GERD-HRQL) scores. All patients had epicutaneous patch testing for nickel and were then instructed to follow a low-nickel diet for 8 weeks regardless of patch test results. GERD-HRQL was recorded at baseline and following 8 weeks of a low-nickel diet. Demographic and clinical data associated with GERD and nickel allergy were recorded. A Wilcoxon signed-rank test and nonparametric analysis of longitudinal data were run to determine statistical significance in pre- and post- GERD-HRQL scores in nickel patch test-positive and negative groups. RESULTS: Nearly all (19/20 [95%]) participants reported reduced GERD symptoms after 8 weeks on a low-nickel diet. Mean total GERD-HRQL, regurgitation, and heartburn scores declined (27.05 ± 16.04, 11.45 ± 6.46, 10.85 ± 8.29). Participants with positive vs. negative patch testing to nickel responded equivalently to a low-nickel diet. CONCLUSIONS: A low-nickel diet improves GERD symptoms, but responsiveness to a low-nickel diet does not correlate with epicutaneous patch testing to nickel. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT03720756.

Smoking is associated with adrenal adenomas and adrenocortical carcinomas: a nationwide multicenter analysis.

MICROABSTRACT: The effect of smoking on adrenal cancer is poorly understood. A clear association of adrenal adenoma and adrenocortical carcinoma with smoking among the United States population is observed. This association points to the possibility of environmental carcinogenic and/or lifestyle factors contributing to adrenal cancer formation. Our results support the association of tobacco use with adrenal adenomas and adrenal cortical carcinoma. BACKGROUND: Smoking has been suggested as a risk factor for adrenal cortical carcinoma (ACC), but this hypothesis has only been inferred from a single study using all types of adrenal cancers including pheochromocytoma, neuroblastoma, as well as ACC. Given the high rate of tobacco use in West Virginia, we hypothesized that smoking might contribute to increased prevalence of ACC. MATERIALS AND METHODS: De-identified institutional review board-exempted records were analyzed in the Surveillance, Epidemiology, and End Results (SEER) Program from 2001-2016 and in patients from the United States nationwide, multicenter TriNetX database of 41,063,707 patients from 2008-2018. In addition, the state-level ratio of smoking to ACC prevalence was computed in all 50 states using data from SEER and the Center for Disease Control. West Virginia Health System data from 2008-2018 was extracted to confirm population-level findings. Melanoma was used as a cancer control in both databases. RESULTS: 6,946 ACC cases were identified. West Virginia had the highest smoking rate and the second highest rate of ACC. A significant association was found between smoking and ACC (Pearson correlation coefficient r = 0.4887, p=.0004). From 2008 to 2018 using TriNetX, 846 ACC and 36,434 AA were extracted. Both adrenal neoplasm cohorts had increased prevalence of tobacco use compared with melanoma controls, where 23.5% were smokers compared to 36.4% and 33.9% in the ACC and AA groups, respectively (p<0.0001 each). CONCLUSION: To our knowledge, this is the first United States population-based study supporting smoking as a risk factor for adrenal carcinogenesis and ACC.