Faculty Bibliography

The atopic dermatitis (AD) Yardstick articles aim to provide an up-to-date review of AD therapy for clinicians. The first two AD Yardstick articles were published in 2018 and 2023. Since the last update, multiple medications have been added to armamentarium of AD. These include roflumilast cream, tapinarof cream, lebrikizumab and nemolizumab. In the current AD Yardstick article, we aim to provide evidence-based information on these new treatments, as well as updated information on previously reviewed therapy. A new feature of the AD Yardstick article is the addition of patient vignettes, which provide practical guide and clinical pearls for clinicians.

BACKGROUND:Myotonic dystrophy type 1 (DM1) is characterized by toxic RNA gain-of-function leading to cardiac conduction defects and life-threatening arrhythmias. Current therapeutic options remain limited. OBJECTIVE:We evaluated the molecular and electrophysiological efficacy of IONIS-486178, an antisense oligonucleotide (ASO) targeting mutant DMPK transcripts in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from a DM1 patient. METHODS:DM1 hiPSC-CMs were treated with IONIS-486178 for 24 hours. Efficacy was assessed via RT-qPCR for DMPK knockdown and splicing analysis, FISH for nuclear foci quantification, western blot for ion channel protein expression, and whole-cell patch-clamp for ionic currents and action potential (AP) characterization. RESULTS:) reduced in DM1 hiPSC-CMs. This electrophysiological rescue correlated with re-expression of the corresponding ion channel proteins. The treatment also normalized AP kinetics and durations and significantly reduced the incidence of arrhythmogenic events. CONCLUSION/CONCLUSIONS:ASO-mediated suppression of DMPK is sufficient to reverse core electrophysiological defects and reduce arrhythmogenic events in a human cellular model of DM1. These findings validate the biological rationale of targeting DMPK to prevent DM1-associated cardiac complications, supporting the continued development of next-generation ASO delivery platforms.

INTRODUCTION/BACKGROUND:The purpose of this study was to determine whether CT Hounsfield units (HUs) as a proxy for bone quality can predict postoperative mechanical complications following surgical treatment of distal humerus fractures. METHODS:One hundred fifty-three patients with both column distal humerus fractures who underwent surgical fixation at single institution and had complete radiographic data available were included. Radiographic measurements included the HU value from the surgical distal humerus as determined by measuring the metaphyseal/supracondylar at the midaxial/coronal/sagittal CT image an average of 1 cm from the articular surface using a freehand region of interest. Zones with fracture lines and cortical impaction were avoided for all measurements. Postoperative complications recorded were implant failure, nonunion, and acute periprosthetic fracture. Patients with and without complications were statistically compared, and binary logistic regression was done to determine if CT HU measurements from the distal humerus were predictive of complications. RESULTS:Five patients (3.3%) developed five mechanical complications, including peri-prosthetic humerus fracture (one), implant failure (two), and nonunion (two). Patients with mechanical complications were more likely to be current smokers (40% vs. 6.8%, P = 0.010). Otherwise, no difference was observed in demographics or AO/Orthopedic Trauma Association classification between the cohorts. Patients with complications had markedly lower HU in the coronal plane (P = 0.031). Regression analysis found that current smoking was associated with an increased risk of mechanical complications (P = 0.041, OR = 1.102, 95% confidence interval [CI], 1.087 to 1.710), whereas a higher coronal HU was associated with a decreased risk of complications (P = 0.048, OR = 0.973, 95% CI, 0.961 to 0.991). CONCLUSION/CONCLUSIONS:A thorough smoking history and CT HU measurements in the coronal plane may identify patients with poorer bone quality at higher risk for postoperative mechanical complications following distal humerus fracture fixation.

Vertebral metastatic disease results from many types of cancer and can have a devastating impact on patient mobility, psychological health, quality of life, and ultimately overall patient survival. However, the development of radiotherapy and surgical techniques has rapidly surged in conjunction with ongoing advances in basic science and translational studies. In this review, we discuss the paradigm shift in our understanding of the epidemiology and treatment algorithms for spinal oncology, ranging from preoperative optimization strategies, radiation and surgical techniques, the utilization of molecular markers and targeted therapeutics in medical oncology, and prognostication tools that underscore a new multidisciplinary approach to spinal oncology care.

The goal of this study was to clarify the contribution of prefrontal cortex activity to men's appraisals, affect states, and decision making in the context of hypothetical heterosexual dating scenarios lacking clear consent. Transcranial direct stimulation (tDCS) was applied to the prefrontal cortex to examine whether it would modify and reduce the likelihood of hypothetical dating violence. Participants (n = 102) responded to first-person vignettes wherein a woman responded either ambiguously or with a refusal to their sexual advance. While responding to the vignettes, participants received sham or active tDCS to modulate prefrontal cortex-mediated responding. Neuromodulation interacted with the communication response type of the woman in the vignette (e.g. ambiguous vs. refusal responses) to influence participants' reports of negative affect (F = 9.57, P = 0.002, Cohen's f²