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INTRODUCTION: Bicuspid aortic valve is the most common congenital cardiac malformation (CCM) in adults and is 30-50 times more frequent in Turner syndrome (TS). We hypothesize that both X and Y chromosome dosages contribute to the prevalence of CCM in TS. The recognition of genotype-phenotype correlations may improve risk stratification of patients with 45,X karyotypes who have cryptic Y chromosome mosaicism. METHODS: Utilizing data and samples from the UTHealth Turner Syndrome Research Registry, we correlated Y chromosome DNA identified by multiplex quantitative PCR and SNP microarrays with the presence of congenital heart lesions. RESULTS: We identified Y chromosome DNA in more than 10% of registry participants, including 2 participants who had no detectable Y DNA by karyotype or SNP microarray. CONCLUSIONS: There were no significant correlations between the presence of Y DNA and CCM.
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Cromosomas Humanos Y , Síndrome de Turner , Humanos , Síndrome de Turner/genética , Síndrome de Turner/complicaciones , Femenino , Cromosomas Humanos Y/genética , Adulto , Polimorfismo de Nucleótido Simple , Cromosomas Humanos X/genética , Mosaicismo , Adolescente , Cardiopatías Congénitas/genética , Cariotipo , Enfermedad de la Válvula Aórtica Bicúspide/genética , Enfermedad de la Válvula Aórtica Bicúspide/complicaciones , Cariotipificación , Niño , Estudios de Cohortes , Estudios de Asociación Genética , Adulto Joven , Válvula Aórtica/anomalíasRESUMEN
Bicuspid aortic valve is the most common congenital heart malformation and predisposes patients to thoracic aortic aneurysms and aortic dissections. Current peripartum guidelines are extrapolated from other heritable causes of thoracic aortic disease and do not account for unique characteristics of bicuspid aortic valve patients. We therefore evaluated the prevalence of maternal and fetal complications of women with early-onset complications of bicuspid aortic valve disease in the UTHealth Bicuspid Aortic Valve Research Registry. We found that the rate of cardiovascular complications was high and that relatively few women received guideline-recommended care.
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This work develops a new multifunctional biocompatible anticancer nanoformulation to provide targeted image-guided cancer-selective therapeutics. It consists of three active covalently bound components: (1) biocompatible nitrogen-doped graphene quantum dots (GQDs) as a multifunctional delivery and imaging platform, (2) hyaluronic acid (HA) unit targeted to the CD44 receptors on a variety of cancer cells, and (3) oxidative stress-based cancer-selective ferrocene (Fc) therapeutic. The biocompatible GQD platform synthesized from glucosamine exhibits high-yield intrinsic fluorescence. It is utilized for tracking Fc-GQD-HA formulation in vitro indicating internalization enhancement in HeLa cells targeted by the HA over non-cancer HEK-293 cells not overexpressing CD44 receptor. Fc-GQD-HA, non-toxic at 1 mg/mL to HEK-293 cells, induces cytotoxic response in HeLa enhanced over time, while therapeutic ROS generation by Fc-GQD-HA is ~3 times greater than that of Fc alone. This outlines the targeted delivery, imaging, and cancer-specific treatment capabilities of the new Fc-GQD-HA formulation enabling desired cancer-focused nanotherapeutic approach.
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Sistemas de Liberación de Medicamentos , Grafito/farmacología , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Doxorrubicina/química , Doxorrubicina/farmacología , Grafito/química , Células HEK293 , Células HeLa , Humanos , Receptores de Hialuranos/antagonistas & inhibidores , Receptores de Hialuranos/genética , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Neoplasias/genética , Neoplasias/patología , Imagen Óptica , Oxidación-Reducción/efectos de los fármacos , Puntos Cuánticos/químicaRESUMEN
Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking new therapies for a variety of solid tumors. ICIs stimulate the host immune system to attack cancer cells. However, this nonspecific immune activation can cause autoimmunity across multiple organ systems-this is referred to as an immune-related adverse event. Vasculitis secondary to ICI administration is an extremely rare event seen in <1% of cases. We identified 2 cases of pembrolizumab-induced acral vasculitis at our institution. The first patient, with stage IV adenocarcinoma of the lung, developed antinuclear antibody-positive vasculitis 4 months after initiation of treatment with pembrolizumab. The second patient had stage IV oropharyngeal cancer and presented with acral vasculitis 7 months after starting pembrolizumab. Unfortunately, both cases resulted in dry gangrene and poor outcomes. Here, we discuss the incidence, pathophysiology, clinical features, treatment, and prognosis of patients with ICI-induced vasculitis with the intention of raising awareness about this rare and potentially fatal immune-related adverse event. Early diagnosis and discontinuation of ICIs are critical for improving clinical outcomes in this situation.