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BACKGROUND: While increasing evidence supports the safety and effectiveness of immunohistochemistry-assisted Mohs micrographic surgery (MMS) for superficially invasive melanoma, there is a paucity of the literature investigating its effect on final defect size. OBJECTIVE: To evaluate the tissue sparing effect of MMS for melanoma. MATERIALS AND METHODS: Three hundred and twenty-eight patients with early-stage (T1a/T1b) cutaneous melanomas treated with MMS from January 2008 to December 2018 were evaluated. Measured defect sizes after Mohs tumor extirpation were compared with anticipated defect size that would result from standard-margin wide local excision (WLE). Average actual versus anticipated defect areas were compared using a paired t-test (95% confidence intervals). RESULTS: The following groups demonstrated a significantly smaller defect area for MMS-treated tumors when compared with anticipated standard-margin WLE defect: All tumors combined (13.8 cm2 vs 10.4 cm2, p < .001), tumors requiring 1 stage (13.6 cm2 vs 10.1 cm2,p < .001), and tumors requiring 2 stages (13.2 cm2 vs 10.5 cm2, p = .004). The majority of patients (83.5%, n = 274) achieved clear margins with 1 stage. CONCLUSION: Immunohistochemistry-assisted MMS for early-stage invasive melanoma is associated with smaller final defect size and overall tissue sparing effect compared with standard WLE margins.
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Background: Mohs micrographic surgery with melanocytic immunohistochemistry (MMS-I) is increasingly utilized for special site melanoma treatment. Yet, frequency and risk factors associated with upstaging of all-stage cutaneous melanomas treated with MMS-I remain undefined. Objective: Determine upstaging frequency and factors associated with tumor upstaging for all-stage melanomas treated with MMS-I. Methods: In this retrospective, single-center case series, all cases of invasive and in situ melanoma treated with MMS-I between 2008 and 2018 were reviewed. Patient and tumor characteristics were recorded and compared between tumors that were and were not upstaged from their initial T stage. Results: Of the 962 melanoma MMS-I cases identified, 44 (4.6%) were upstaged, including 5.6% of in situ and 2.5% of invasive tumors. Risk factors for upstaging included lack of excisional intent at the time of initial biopsy (P < .01), nonlentigo maligna subtype (P = .03), female sex (P = .02), and initial in situ diagnosis (P = .03). Nonstatistically significant characteristics evaluated included patient age (P = .97), initial Breslow depth (P = .18), and biopsy type (P = .24). Limitations: Retrospective study design. Conclusions: All-stage cutaneous melanomas treated with MMS-I are associated with low upstaging rates. Tumor upstaging is associated with lack of excisional intent, female sex, and in situ tumors.
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Lipids secreted by the meibomian glands (MGs) of the eyelids are essential to the protection of the eye's surface. An altered meibum composition represents the primary cause of evaporative dry eye disease (DED). Despite the critical importance of the meibum, its biosynthetic pathways and the roles of individual lipid components remain understudied. Here, we report that the genetic deletion of Acyl-CoA:wax alcohol acyltransferase 2 (AWAT2) causes the obstruction of MGs and symptoms of evaporative DED in mice. The lipid composition of the meibum isolated from Awat2-/- mice revealed the absence of wax esters, which was accompanied by a compensatory overproduction of cholesteryl esters. The resulting increased viscosity of meibum led to the dilation of the meibomian ducts, and the progressive degeneration of the MGs. Overall, we provide evidence for the main physiological role of AWAT2 and establish Awat2-/- mice as a model for DED syndrome that can be used in studies on tear film-oriented therapies.
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Aciltransferasas/genética , Síndromes de Ojo Seco/genética , Aciltransferasas/deficiencia , Aciltransferasas/metabolismo , Animales , Síndromes de Ojo Seco/metabolismo , Síndromes de Ojo Seco/patología , Ésteres/metabolismo , Aparato Lagrimal/metabolismo , Aparato Lagrimal/patología , Ratones , Ratones Endogámicos C57BL , Lágrimas/química , Lágrimas/metabolismo , ViscosidadRESUMEN
INTRODUCTION: Although various treatment options for hidrocystomas have been described, the comparative efficacy of these treatments is poorly understood. METHODS: We conducted a systematic review of all articles describing the treatment of hidrocystomas. Treatment modalities were categorized as destructive surgical procedures, skin-directed therapies, systemic medical therapies, general measures, or combined. Patient and tumor characteristics, as well as response rate, recurrence rate, and adverse effects, were extracted from each article. RESULTS: A total of 94 articles involving 192 patients and 255 unique treatment events were included in the final analysis. Destructive surgical procedures had an overall response rate and recurrence rate of 92.9% and 10.8%, respectively. Skin-directed therapies had an overall response rate of 72.6%. The overall response rate to systemic medical therapies was 71.4%. Solitary hidrocystomas were primarily treated with destructive surgical procedures, including excision, which was associated with a 4.7% recurrence rate. Multiple hidrocystomas were successfully treated with a variety of therapies, including destructive surgical procedures and skin-directed therapies requiring ongoing or repeated therapy. CONCLUSIONS: Excision has the highest efficacy for solitary hidrocystomas. A number of therapies have shown efficacy for multiple hidrocystomas, including lasers, intracystic trichloroacetic acid, intracystic hypertonic glucose, topical and oral anticholinergics, and botulinum toxin. Aluminum chloride is associated with a low response rate. Larger comparative studies are needed to further evaluate the optimal treatments for solitary and multiple hidrocystomas.
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Hidrocistoma/terapia , Neoplasias de las Glándulas Sudoríparas/terapia , HumanosRESUMEN
Cellular retinol-binding proteins (CRBPs) facilitate the uptake and intracellular transport of vitamin A. They integrate retinoid metabolism, playing an important role in regulating the synthesis of bioactive vitamin A metabolites. Thus, CRBPs constitute potential pharmacological targets to modulate cellular retinoid status that in turn may have applications in the treatment of certain immunological, metabolic, and ocular disorders. Here we identify abnormal cannabidiol (abn-CBD) as a nonretinoid inhibitor of cellular retinol-binding protein 1 (CRBP1). X-ray crystal structures of CRBP1 in complex with abn-CBD and its derivatives revealed a distinctive mode of protein-ligand interaction and provided a molecular basis for the high affinity and selectivity of this compound. We demonstrated that abn-CBD modulates the flux of retinoids via the retinoid cycle in vivo. Furthermore, the biological activity of abn-CBD was evidenced by its ability to protect against light-induced retinal damage in Balb/cJ mice. Altogether, our findings indicate that targeting selected CRBPs with a small-molecule inhibitor can potentially lead to the development of new therapeutic agents to counteract diseases with etiologies involving imbalance in retinoid metabolism or signaling.
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Resorcinoles/química , Resorcinoles/metabolismo , Degeneración Retiniana/prevención & control , Retinoides/metabolismo , Proteínas Celulares de Unión al Retinol/antagonistas & inhibidores , Vitamina A/metabolismo , Secuencia de Aminoácidos , Animales , Transporte Biológico/efectos de los fármacos , Línea Celular , Evaluación Preclínica de Medicamentos/métodos , Humanos , Isomerismo , Cinética , Ligandos , Luz , Ratones Endogámicos BALB C , Oxidación-Reducción , Unión Proteica , Proteínas Celulares de Unión al Retinol/genética , Transducción de Señal , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/metabolismo , Relación Estructura-ActividadRESUMEN
Aorto-enteric fistula (AEF) is a rare life-threatening condition. Early recognition and diagnosis are of paramount importance to improve outcome. In this article four cases of AEF with relevant pre- and post-procedural images are presented to demonstrate the utility of cross-sectional imaging in the work-up of AEF. The literature is reviewed to describe the typical presentation of AEF, the diagnostic work-up of AEF, and the different methods used to treat AEF. Endovascular repair of AEF is gaining increasing attention due to its decreased short-term mortality compared to open surgical techniques.
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The recently published Prevention of Serious Adverse Events Following Angiography (PRESERVE) trial is presently the largest and most comprehensive clinical trial comparing commonly applied strategies for prevention of iodinated contrast-induced acute kidney injury in high-risk patients. The fundamental conclusion of the PRESERVE trial is that oral acetylcysteine and i.v. sodium bicarbonate are not superior to simple i.v. hydration with isotonic saline for the prevention of contrast-induced renal sequelae. In this commentary, we discuss the results in the context of selected past major trials, and provide insights into the strengths and potential weaknesses of the PRESERVE trial. In the future, developing individualized preventive approaches to avoid contrast-induced acute kidney injury for different patient populations is recommended.
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Acetilcisteína/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Angiografía , Medios de Contraste/efectos adversos , Depuradores de Radicales Libres/uso terapéutico , Bicarbonato de Sodio/uso terapéutico , Administración Intravenosa , Administración Oral , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Especies Reactivas de Oxígeno/toxicidad , Proyectos de InvestigaciónRESUMEN
Endoleaks are a common complication of endovascular aortic repair (EVAR). As a result, patients require lifelong imaging surveillance following EVAR. In current clinical practice, evaluation for endoleaks is predominantly performed with CT angiography (CTA). Due to the significant cumulative radiation burden associated with repetitive CTA imaging, as well as the repeated administration of nephrotoxic contrast agent, contrast-enhanced ultrasound (CEUS) and magnetic resonance angiography (MRA) have evolved as potential modalities for lifelong surveillance post-EVAR. In this paper, multimodality imaging, including CTA, CEUS and MRA, for the surveillance of endoleaks is discussed. Further, new CTA techniques for radiation reduction are elaborated. Additionally, imagery for three cases of aortic endoleak detection using CTA and five cases using MRA are presented. Imaging for different types of endoleaks with CTA, MRA and CEUS are presented. For lifelong endoleak surveillance post-EVAR, CTA is still regarded as the imaging modality of choice. However, advancements in CEUS and MRA technique enable partial replacement of CTA in certain patients.