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1.
Article in English | MEDLINE | ID: mdl-38148442

ABSTRACT

PURPOSE: The demographic proportions of plastic surgery trials approximating real-world disease have not well been studied. Judicious trial representation is essential in evaluation of treatments across diverse patient populations. Herein, we investigate sex, racial, and ethnic disparities in patient enrollment across burn trials. METHODS: Cross-sectional analysis of participants enrolled in high-quality, with reduced risk of bias, randomized controlled trials (RCT) on burns registered on clinicaltrials.gov under the query "burn." Completed RCTs reporting at least two demographic groups, employing double masking or greater, and with results accessible through the registry or publications were included. Trial characteristics (sponsor country, site location, initiation year, study phase, masking) and demographic data (sex, race, ethnicity per US reporting guidelines) were collected. The Global Burden of Disease database provided sex-based burn disease burdens. The primary outcome was the population-to-prevalence ratio of enrolled female participants. Secondary outcomes included representation of racial and ethnic populations as related to study blinding, phase, and study/sponsor locations. RESULTS: Of 546 records, 39 trials met the inclusion criteria (2919 participants). All trials reported sex demographics, with females comprising 37.02% of all participants (PPR = 0.71, 95% CI [0.59, 0.82], likely indicating underrepresentation against their empiric disease burden). Only 7 and 9 trials reported ethnicity and race, respectively, although not comprehensively. Among trials reporting race or ethnicity, Caucasians and Black persons comprised 57.52% and 21.80% of participants, respectively, while only 9.80% had Hispanic/Latino ethnicity. Severe underreporting of race and ethnicity precluded much of secondary significance testing across study variables. CONCLUSIONS: Females are likely underrepresented in high-quality, US-registered burn trials, unreflective of their real-world disease burden. Further, severe underreporting of race and ethnicity was noted. Future trials should enroll diverse demographics and equitable populations for promotion of study generalizability.

2.
Cardiovasc Res ; 119(15): 2522-2535, 2023 11 25.
Article in English | MEDLINE | ID: mdl-37739930

ABSTRACT

AIMS: Long QT syndrome type 2 (LQTS2) is associated with inherited variants in the cardiac human ether-à-go-go-related gene (hERG) K+ channel. However, the pathogenicity of hERG channel gene variants is often uncertain. Using CRISPR-Cas9 gene-edited hiPSC-derived cardiomyocytes (hiPSC-CMs), we investigated the pathogenic mechanism underlying the LQTS-associated hERG R56Q variant and its phenotypic rescue by using the Type 1 hERG activator, RPR260243. METHODS AND RESULTS: The above approaches enable characterization of the unclear causative mechanism of arrhythmia in the R56Q variant (an N-terminal PAS domain mutation that primarily accelerates channel deactivation) and translational investigation of the potential for targeted pharmacologic manipulation of hERG deactivation. Using perforated patch clamp electrophysiology of single hiPSC-CMs, programmed electrical stimulation showed that the hERG R56Q variant does not significantly alter the mean action potential duration (APD90). However, the R56Q variant increases the beat-to-beat variability in APD90 during pacing at constant cycle lengths, enhances the variance of APD90 during rate transitions, and increases the incidence of 2:1 block. During paired S1-S2 stimulations measuring electrical restitution properties, the R56Q variant was also found to increase the variability in rise time and duration of the response to premature stimulations. Application of the hERG channel activator, RPR260243, reduces the APD variance in hERG R56Q hiPSC-CMs, reduces the variability in responses to premature stimulations, and increases the post-repolarization refractoriness. CONCLUSION: Based on our findings, we propose that the hERG R56Q variant leads to heterogeneous APD dynamics, which could result in spatial dispersion of repolarization and increased risk for re-entry without significantly affecting the average APD90. Furthermore, our data highlight the antiarrhythmic potential of targeted slowing of hERG deactivation gating, which we demonstrate increases protection against premature action potentials and reduces electrical heterogeneity in hiPSC-CMs.


Subject(s)
Ether-A-Go-Go Potassium Channels , Long QT Syndrome , Humans , Ether-A-Go-Go Potassium Channels/genetics , Long QT Syndrome/genetics , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/prevention & control , Myocytes, Cardiac , Action Potentials , Ethers , ERG1 Potassium Channel/genetics
3.
Ophthalmic Plast Reconstr Surg ; 39(2): e64-e67, 2023.
Article in English | MEDLINE | ID: mdl-36735325

ABSTRACT

Lacrimal gland cysts are rare clinical entities in the pediatric population. Herein is described a 6-year-old male patient presenting with progressive left upper lid ptosis, found to have a large ipsilateral superotemporal orbital mass. Diagnosis of a giant lacrimal gland cyst was confirmed excisional biopsy. Despite the resolution of mechanical blepharoptosis, the patient maintained visual acuity limitation due to suspected deprivation amblyopia. The pathophysiology and clinical manifestations of lacrimal gland cysts in the pediatric population are reviewed to emphasize the importance of expedited identification and management in this patient cohort.


Subject(s)
Blepharoptosis , Cysts , Eye Neoplasms , Lacrimal Apparatus Diseases , Lacrimal Apparatus , Orbital Diseases , Male , Humans , Child , Lacrimal Apparatus/pathology , Cysts/diagnosis , Blepharoptosis/diagnosis , Orbital Diseases/complications , Lacrimal Apparatus Diseases/diagnosis
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