Background

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe dermatologic emergencies. Although pregnant women comprise a subset of individuals at risk for SJS and TEN development, little is known with regard to outcomes and treatment.

Objective

This study aimed to conduct a systematic review to characterize the risk factors, outcomes, and treatment of SJS and TEN in pregnant patients and newborns.

Methods

A primary literature search was conducted using PubMed in September 2019, using the following search terms entered in separate pairs: pregnant or pregnancy and stevens-johnson or SJS or toxic epidermal necrolysis. Reviews, studies in a language other than English, and articles not including pregnant patients were excluded.

Results

Twenty-six articles were included for review, including a total of 177 patients. The average maternal age for a reaction was 29.9 years, gestational age was 24.9 weeks, and time to reaction after drug initiation was 27.5 days. Approximately 85% of pregnant women in this review were infected with HIV. The most common causative medications were antiretroviral therapy (90% of all cases), antibiotics (3%), and gestational drugs (2%). Of the 94 cases in which outcome data were available, the survival rates of pregnant women and newborns after delivery were 98% and 96%, respectively. Withdrawal of the offending agent and supportive care was often sufficient for treatment, but antibiotics, steroids, and intravenous immunoglobulin were implemented in some cases. Complications included preterm labor, vaginal stenosis, and vaginal adhesions.

Conclusion

Given the predominance of studies focusing on the subset of pregnant patients who are infected with HIV, SJS and TEN is most commonly reported in young patients after antiretroviral therapy, primarily nevirapine. Overall mortality is lower than that of the general population, but similar to the expected mortality rates of younger adults. Early recognition and withdrawal of the offending agent is essential to mitigate the distinct consequences of these conditions in the pregnant population.

Because there are important distinctions between ablative and non-ablative laser resurfacing, accurate and effective patient education is paramount. However, as more patients use the internet as a resource for medical information, little is known about the content and readability of these sources. Thus, we sought to evaluate the readability of major online resources about laser resurfacing while recognizing the recommendations by the American Medical Association and National Institutes of Health. An internet search for the term "Laser Resurfacing" was performed. The first 9 results were identified, patient information from each of these 9 sites were downloaded, and a total of 25 articles were examined. Readability was analyzed using 7 different established tests. Analysis demonstrated an average grade level of at least 9th grade, with all articles exceeding the recommended 6th grade reading level, emphasizing that these resources are too challenging for many patients to read and comprehend. Such materials may hamper appropriate decision-making in patients considering the use of a laser for their dermatologic conditions. The potential detrimental effect on the opinion, participation, and satisfaction of laser resurfacing should spur dermatologists to be more critical of online patient materials and motivated to produce more appropriate resources.

Healthcare access greatly impacts skin cancer diagnosis and mortality rates. Recognition of current disparities in Mohs micrographic surgery (MMS) access can assist future policy and clinical decisions to correct them. For the years 2014-2018, the CPT codes for MMS (17,311 and 17,313) were counted on a per county level across the United States per the Medicare Centers for Medicare & Medicaid Services (CMS) Medicare Prescriber Database. Any county with 0 MMS CPT codes recorded were classified as without MMS cases. MMS hotspots were identified as counties that possessed a high average number of MMS cases compared to the national average, while also being surrounded by counties that possessed a low average number of MMS cases compared to the national average. Three thousand eighty-four counties in the United States were analyzed; 785 (25%) counties were designated as with MMS cases and 2301 (75%) without MMS cases. There were no significant differences in age, ethnicity distribution, or cost per enrollee between the two designations. 74% of counties with MMS cases were considered urban, while only 25% of those without cases were urban (p < 0.01). The median household income was markedly higher in counties with MMS cases ($71,428 vs. $58,913, p < 0.01). With respect to education, more individuals in counties with MMS cases possessed their General Education Development (GED) (89% vs. 86%, p < 0.01) or a college degree (30% vs. 19%, p < 0.01). Forty-nine counties were considered MMS hotspots. The density of MMS procedures varies greatly based on geography, maintaining the urban-rural disparity matched by the distribution of MMS surgeons. Additionally, there remains a wide income and educational gap between counties with and without MMS. Identifying MMS hotspots may facilitate further investigation into potential surgical access disparities.

Hydrogen tunneling in enzymatic C-H activation requires a dynamical sampling among ground-state enzyme-substrate (E-S) conformations, which transiently generates a tunneling-ready state (TRS). The TRS is characterized by a hydrogen donor-acceptor distance (DAD) of 2.7 Å, ∼0.5 Å shorter than the dominant DAD of optimized ground states. Recently, a high-resolution, 13C electron-nuclear double-resonance (ENDOR) approach was developed to characterize the ground-state structure of the complex of the linoleic acid (LA) substrate with soybean lipoxygenase (SLO). The resulting enzyme-substrate model revealed two ground-state conformers with different distances between the target C11 of LA and the catalytically active cofactor [Fe(III)-OH]: the active conformer a, with a van der Waals DAD of 3.1 Å between C11 and metal-bound hydroxide, and an inactive conformer b, with a distance that is almost 1 Å longer. Herein, the structure of the E-S complex is examined for a series of six variants in which subtle structural modifications of SLO have been introduced either at a hydrophobic side chain near the bound substrate or at a remote residue within a protein network whose flexibility influences hydrogen transfer. A remarkable correlation is found between the ENDOR-derived population of the active ground-state conformer a and the kinetically derived differential enthalpic barrier for D versus H transfer, ΔEa, with the latter increasing as the fraction of conformer a decreases. As proposed, ΔEa provides a ruler for the DAD within the TRS. ENDOR measurements further corroborate the previous identification of a dynamical network coupling the buried active site of SLO to the surface. This study shows that subtle imperfections within the initial ground-state structures of E-S complexes are accompanied by compromised geometries at the TRS.

The molybdenum trisamidoamine (TAA) complex [Mo] {[3,5-(2,4,6-i-Pr₃C₆H₂)₂C₆H₃NCH₂CH₂N]Mo} carries out catalytic reduction of N₂ to ammonia (NH₃) by protons and electrons at room temperature. A key intermediate in the proposed [Mo] nitrogen reduction cycle is nitridomolybdenum(VI), [Mo(VI)]N. The addition of [e^-/H⁺] to [Mo(VI)]N to generate [Mo(V)]NH might, in principle, follow one of three possible pathways: direct proton-coupled electron transfer; H⁺ first and then e^-; e^- and then H⁺. In this study, the paramagnetic Mo(V) intermediate {[Mo]N}^- and the [Mo]NH transfer product were generated by irradiating the diamagnetic [Mo]N and {[Mo]NH}⁺ Mo(VI) complexes, respectively, with γ-rays at 77 K, and their electronic and geometric structures were characterized by electron paramagnetic resonance and electron nuclear double resonance spectroscopies, combined with quantum-chemical computations. In combination with previous X-ray studies, this creates the rare situation in which each one of the four possible states of [e^-/H⁺] delivery has been characterized. Because of the degeneracy of the electronic ground states of both {[Mo(V)]N}^- and [Mo(V)]NH, only multireference-based methods such as the complete active-space self-consistent field (CASSCF) and related methods provide a qualitatively correct description of the electronic ground state and vibronic coupling. The molecular g values of {[Mo]N}^- and [Mo]NH exhibit large deviations from the free-electron value g_e. Their actual values reflect the relative strengths of vibronic and spin-orbit coupling. In the course of the computational treatment, the utility and limitations of a formal two-state model that describes this competition between couplings are illustrated, and the implications of our results for the chemical reactivity of these states are discussed.

Hydrogen tunneling in enzymatic C-H activation requires a dynamical sampling among ground-state enzyme-substrate (E-S) conformations, which transiently generates a tunneling-ready state (TRS). The TRS is characterized by a hydrogen donor-acceptor distance (DAD) of 2.7 Å, ∼0.5 Å shorter than the dominant DAD of optimized ground states. Recently, a high-resolution, ¹³C electron-nuclear double-resonance (ENDOR) approach was developed to characterize the ground-state structure of the complex of the linoleic acid (LA) substrate with soybean lipoxygenase (SLO). The resulting enzyme-substrate model revealed two ground-state conformers with different distances between the target C11 of LA and the catalytically active cofactor [Fe(III)-OH]: the active conformer "a", with a van der Waals DAD of 3.1 Å between C11 and metal-bound hydroxide, and an inactive conformer "b", with a distance that is almost 1 Å longer. Herein, the structure of the E-S complex is examined for a series of six variants in which subtle structural modifications of SLO have been introduced either at a hydrophobic side chain near the bound substrate or at a remote residue within a protein network whose flexibility influences hydrogen transfer. A remarkable correlation is found between the ENDOR-derived population of the active ground-state conformer a and the kinetically derived differential enthalpic barrier for D versus H transfer, ΔE_a, with the latter increasing as the fraction of conformer a decreases. As proposed, ΔE_a provides a "ruler" for the DAD within the TRS. ENDOR measurements further corroborate the previous identification of a dynamical network coupling the buried active site of SLO to the surface. This study shows that subtle imperfections within the initial ground-state structures of E-S complexes are accompanied by compromised geometries at the TRS.