Recurrent erythema multiforme-like reaction secondary to recurrent poison ivy exposure.

A 14-year-old boy developed an erythema multiforme-like reaction following Toxicodendron radicans (poison ivy) allergic contact dermatitis three separate times over the course of 3 years. The severity of each erythema multiforme-like reaction corresponded to the severity of the allergic contact dermatitis which preceded it.

Randomized Controlled Study of Cooled vs Room-Temperature Artificial Tears for Reducing Ocular Surface Irritation After Intravitreal Injection.

Purpose: To evaluate the efficacy of cooled vs room-temperature artificial tears in reducing ocular discomfort after intravitreal injections (IVIs). Methods: Patients receiving a standard intravitreal injection in the retina clinic who met the eligibility criteria and provided informed consented were enrolled in the study. Patients were randomized to the cooled tears or room-temperature tears intervention group. Both groups rated their ocular discomfort following IVI after cooled or room-temperature tears were administered. Results: The cooled group comprised 48 patients and the room-temperature group, 61 patients. There was no significant difference in the reduction of ocular discomfort between the cooled vs room-temperature artificial tears groups (P = .387). In addition, there was a similar level of reduction in ocular discomfort after either intervention (P = .681) regardless of whether or not the patients routinely used artificial tears after previous IVIs. Conclusions: Cooled tears provided no additional benefit in reducing ocular discomfort post-IVI compared with room-temperature tears. Baseline tear use after an IVI may have no true benefit other than a potential placebo effect, recall bias, or both.

Single-Cell Discovery and Multiomic Characterization of Therapeutic Targets in Multiple Myeloma.

Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which were previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA sequencing, flow cytometry, and proteomic mass spectrometry of MM cell lines and patient BM, demonstrating high overall concordance across data types. Independent discovery using bulk RNA sequencing reiterated top candidates, further affirming the ability of single-cell transcriptomics to accurately capture marker expression despite limitations in sample size or sequencing depth. Target dynamics and heterogeneity were further examined using both transcriptomic and immuno-imaging methods. In summary, this study presents a robust and broadly applicable strategy for identifying tumor markers to better inform the development of targeted cancer therapy. SIGNIFICANCE: Single-cell transcriptomic profiling and multiomic cross-validation to uncover therapeutic targets identifies 38 myeloma marker genes, including 11 transcribing surface proteins with previously uncharacterized potential for targeted antitumor therapy.

TFEB activation in macrophages attenuates postmyocardial infarction ventricular dysfunction independently of ATG5-mediated autophagy.

Lysosomes are at the epicenter of cellular processes critical for inflammasome activation in macrophages. Inflammasome activation and IL-1ß secretion are implicated in myocardial infarction (MI) and resultant heart failure; however, little is known about how macrophage lysosomes regulate these processes. In mice subjected to cardiac ischemia/reperfusion (IR) injury and humans with ischemic cardiomyopathy, we observed evidence of lysosomal impairment in macrophages. Inducible macrophage-specific overexpression of transcription factor EB (TFEB), a master regulator of lysosome biogenesis (Mϕ-TFEB), attenuated postinfarction remodeling, decreased abundance of proinflammatory macrophages, and reduced levels of myocardial IL-1ß compared with controls. Surprisingly, neither inflammasome suppression nor Mϕ-TFEB-mediated attenuation of postinfarction myocardial dysfunction required intact ATG5-dependent macroautophagy (hereafter termed "autophagy"). RNA-seq of flow-sorted macrophages postinfarction revealed that Mϕ-TFEB upregulated key targets involved in lysosomal lipid metabolism. Specifically, inhibition of the TFEB target, lysosomal acid lipase, in vivo abrogated the beneficial effect of Mϕ-TFEB on postinfarction ventricular function. Thus, TFEB reprograms macrophage lysosomal lipid metabolism to attenuate remodeling after IR, suggesting an alternative paradigm whereby lysosome function affects inflammation.