Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe mucocutaneous reaction with few large cohorts reported. This multicenter retrospective study included patients with SJS/TEN seen by inpatient consultative dermatologists at 18 academic medical centers in the United States. A total of 377 adult patients with SJS/TEN between January 1, 2000 and June 1, 2015 were entered, including 260 of 377 (69%) from 2010 onward. The most frequent cause of SJS/TEN was medication reaction in 338 of 377 (89.7%), most often to trimethoprim/sulfamethoxazole (89/338; 26.3%). Most patients were managed in an intensive care (100/368; 27.2%) or burn unit (151/368; 41.0%). Most received pharmacologic therapy (266/376; 70.7%) versus supportive care alone (110/376; 29.3%)-typically corticosteroids (113/266; 42.5%), intravenous immunoglobulin (94/266; 35.3%), or both therapies (54/266; 20.3%). Based on day 1 SCORTEN predicted mortality, approximately 78 in-hospital deaths were expected (77.7/368; 21%), but the observed mortality of 54 patients (54/368; 14.7%) was significantly lower (standardized mortality ratio = 0.70; 95% confidence interval = 0.58-0.79). Stratified by therapy received, the standardized mortality ratio was lowest among those receiving both steroids and intravenous immunoglobulin (standardized mortality ratio = 0.52; 95% confidence interval 0.21-0.79). This large cohort provides contemporary information regarding US patients with SJS/TEN. Mortality, although substantial, was significantly lower than predicted. Although the precise role of pharmacotherapy remains unclear, co-administration of corticosteroids and intravenous immunoglobulin, among other therapies, may warrant further study.
Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As III ). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As III through the modulation of chromatin. The role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis was further explored in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16, and induced sensitivity to As III and to its more toxic metabolite monomethylarsonous acid (MMA III ) at doses relevant to high environmental human exposures. In addition, both As III and MMA III treatments decreased global H4K16 acetylation levels in a dose-and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.
BackgroundIn humans, inorganic arsenic (iAs) is metabolized to methylated arsenical species in a multistep process mainly mediated by arsenic (+3 oxidation state) methyltransferase (AS3MT). Among these metabolites is monomethylarsonous acid (MMAIII), the most toxic arsenic species. A recent study in As3mt-knockout mice suggests that unidentified methyltransferases could be involved in alternative iAs methylation pathways. We found that yeast deletion mutants lacking MTQ2 were highly resistant to iAs exposure. The human ortholog of the yeast MTQ2 is N-6 adenine-specific DNA methyltransferase 1 (N6AMT1), encoding a putative methyltransferase.ObjectiveWe investigated the potential role of N6AMT1 in arsenic-induced toxicity.MethodsWe measured and compared the cytotoxicity induced by arsenicals and their metabolic profiles using inductively coupled plasma–mass spectrometry in UROtsa human urothelial cells with enhanced N6AMT1 expression and UROtsa vector control cells treated with different concentrations of either iAsIII or MMAIII.ResultsN6AMT1 was able to convert MMAIII to the less toxic dimethylarsonic acid (DMA) when overexpressed in UROtsa cells. The enhanced expression of N6AMT1 in UROtsa cells decreased cytotoxicity of both iAsIII and MMAIII. Moreover, N6AMT1 is expressed in many human tissues at variable levels, although at levels lower than those of AS3MT, supporting a potential participation in arsenic metabolism in vivo.ConclusionsConsidering that MMAIII is the most toxic arsenical, our data suggest that N6AMT1 has a significant role in determining susceptibility to arsenic toxicity and carcinogenicity because of its specific activity in methylating MMAIII to DMA and other unknown mechanisms.
Background Both clinicians and patients have increasingly turned to telemedicine to improve care access, even in physical examination–dependent specialties such as dermatology. However, little is known about whether teledermatology supports effective and timely transitions from inpatient to outpatient care, which is a common care coordination gap. Objective Using mixed methods, this study sought to retrospectively evaluate how teledermatology affected clinic capacity, scheduling efficiency, and timeliness of follow-up care for patients transitioning from inpatient to outpatient dermatology care. Methods Patient-level encounter scheduling data were used to compare the number and proportion of patients who were scheduled and received in-clinic or video dermatology follow-ups within 14 and 90 days after discharge across 3 phases: June to September 2019 (before teledermatology), June to September 2020 (early teledermatology), and February to May 2021 (sustained teledermatology). The time from discharge to scheduling and completion of patient follow-up visits for each care modality was also compared. Dermatology clinicians and schedulers were also interviewed between April and May 2021 to assess their perceptions of teledermatology for postdischarge patients. Results More patients completed follow-up within 90 days after discharge during early (n=101) and sustained (n=100) teledermatology use than at baseline (n=74). Thus, the clinic’s capacity to provide follow-up to patients transitioning from inpatient increased from baseline by 36% in the early (101 from 74) and sustained (100 from 74) teledermatology periods. During early teledermatology use, 61.4% (62/101) of the follow-ups were conducted via video. This decreased significantly to 47% (47/100) in the following year, when COVID-19–related restrictions started to lift (P=.04), indicating more targeted but still substantial use. The proportion of patients who were followed up within the recommended 14 days after discharge did not differ significantly between video and in-clinic visits during the early (33/62, 53% vs 15/39, 38%; P=.15) or sustained (26/53, 60% vs 28/47, 49%; P=.29) teledermatology periods. Interviewees agreed that teledermatology would continue to be offered. Most considered postdischarge follow-up patients to be ideal candidates for teledermatology as they had undergone a recent in-person assessment and might have difficulty attending in-clinic visits because of competing health priorities. Some reported patients needing technological support. Ultimately, most agreed that the choice of follow-up care modality should be the patient’s own. Conclusions Teledermatology could be an important tool for maintaining accessible, flexible, and convenient care for recently discharged patients needing follow-up care. Teledermatology increased clinic capacity, even during the pandemic, although the timeliness of care transitions did not improve. Ultimately, the care modality should be determined through communication with patients to incorporate their and their caregivers’ preferences.
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