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1.
JAMA Otolaryngol Head Neck Surg ; 148(6): 531-539, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35511129

RESUMEN

Importance: Papillary thyroid microcarcinomas (PTMCs) have been associated with increased thyroid cancer incidence in recent decades. Total thyroidectomy (TT) has historically been the primary treatment, but current guidelines recommend hemithyroidectomy (HT) for select low-risk cancers; however, the risk-benefit ratio of the 2 operations is incompletely characterized. Objective: To compare surgical complication rates between TT and HT for PTMC treatment. Data Sources: SCOPUS, Medline via the PubMed interface, and the Cochrane Central Register of Controlled Trials (CENTRAL); through January 1, 2021, with no starting date restriction. Terms related to papillary thyroid carcinoma and its treatment were used for article retrieval. This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. Study Selection: Original investigations of adults reporting primary surgical treatment outcomes in PTMC and at least 1 complication of interest were included. Articles evaluating only secondary operations or non-open surgical approaches were excluded. Study selection, data extraction, and risk of bias assessment were performed by 2 independent reviewers and conflicts resolved by a senior reviewer. Data Extraction and Synthesis: Pooled effect estimates were calculated using a random-effects inverse-variance weighting model. Main Outcomes and Measures: Cancer recurrence and site, mortality (all-cause and disease-specific), vocal fold paralysis, hypoparathyroidism, and hemorrhage/hematoma. Risk of bias was assessed using the McMaster Quality Assessment Scale of Harms scale. Results: In this systematic review and meta-analysis, 17 studies were analyzed and included 1416 patients undergoing HT and 2411 patients undergoing TT (HT: pooled mean [SD] age, 47.0 [10.0] years; 1139 [84.6%] were female; and TT: pooled mean [SD] age, 48.8 [10.0] years; 1671 [77.4%] were female). Patients undergoing HT had significantly lower risk of temporary vocal fold paralysis compared with patients undergoing TT (3.3% vs 4.5%) (weighted risk ratio [RR], 0.4; 95% CI, 0.2-0.7), temporary hypoparathyroidism (2.2% vs 21.3%) (weighted RR, 0.1; 95% CI, 0.0-0.4), and permanent hypoparathyroidism (0% vs 1.8%) (weighted RR, 0.2; 95% CI, 0.0-0.8). Contralateral lobe malignant neoplasm recurrence was 2.3% in the HT group, while no such events occurred in the TT group. Hemithyroidectomy was associated with a higher overall recurrence rate (3.8% vs 1.0%) (weighted RR, 2.6; 95% CI, 1.3-5.4), but there was no difference in recurrence in the thyroid bed or neck. Conclusions and Relevance: The results of this systematic review and meta-analysis help characterize current knowledge of the risk-benefit ratio of HT vs TT for treatment of PTMC and provide data that may have utility for patient counseling surrounding treatment decisions.


Asunto(s)
Hipoparatiroidismo , Neoplasias de la Tiroides , Parálisis de los Pliegues Vocales , Carcinoma Papilar , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Estudios Observacionales como Asunto , Neoplasias de la Tiroides/patología , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Parálisis de los Pliegues Vocales/epidemiología , Parálisis de los Pliegues Vocales/etiología , Parálisis de los Pliegues Vocales/cirugía
2.
Gene Ther ; 29(1-2): 69-80, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34012109

RESUMEN

Using genetic tools to study the functional roles of molecularly specified neuronal populations in the primate brain is challenging, primarily because of specificity and verification of virus-mediated targeting. Here, we report a lentivirus-based system that helps improve specificity and verification by (a) targeting a selected molecular mechanism, (b) in vivo reporting of expression, and (c) allowing the option to independently silence all regional neural activity. Specifically, we modulate cholinergic signaling of striatal interneurons by shRNAmir and pair it with hM4Di_CFP, a chemogenetic receptor that can function as an in vivo and in situ reporter. Quantitative analyses by visual and deep-learning assisted methods show an inverse linear relation between hM4Di_CFP and ChAT protein expression for several shRNAmir constructs. This approach successfully applies shRNAmir to modulating gene expression in the primate brain and shows that hM4Di_CFP can act as a readout for this modulation.


Asunto(s)
Cuerpo Estriado , Interneuronas , Animales , Cuerpo Estriado/metabolismo , Interneuronas/metabolismo , Neuronas , Primates/genética , Interferencia de ARN
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