RESUMO
OBJECTIVE: To investigate the role of NN414, a selective KATP channel opener for the Kir6.2/SUR1 channel subtype found in neurons and ß-pancreatic cells, in inducing migraine attacks in individuals with migraine without aura. METHODS: Thirteen participants were randomly allocated to receive NN414 and placebo on two days separated by at least one week. The primary endpoint was the difference in the incidence of migraine attacks after NN414 compared with placebo. The secondary endpoints were the difference in the area under the curve for headache intensity scores, middle cerebral artery blood flow velocity (VMCA), superficial temporal artery diameter, heart rate and mean arterial pressure. RESULTS: Twelve participants completed the study, with two (16.6%) reporting migraine attacks after NN414 compared to one (8.3%) after placebo (p = 0.53). The area under the curve for headache intensity, VMCA, superficial temporal artery diameter, heart rate and mean arterial pressure did not differ between NN414 and placebo (p > 0.05, all comparisons). CONCLUSION: The lack of migraine induction upon activation of the Kir6.2/SUR1 channel subtype suggests it may not contribute to migraine pathogenesis. Our findings point to KATP channel blockers that target the Kir6.1/SUR2B subtype, found in cerebral vasculature, as potential candidates for innovative antimigraine treatments.Registration number: NCT04744129.
Assuntos
Canais KATP , Transtornos de Enxaqueca , Humanos , Feminino , Adulto , Masculino , Canais KATP/metabolismo , Método Duplo-Cego , Transtornos de Enxaqueca/metabolismo , Adulto Jovem , Pessoa de Meia-Idade , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Piridinas/farmacologia , PiperidinasRESUMO
BACKGROUND: To prospectively develop and validate the T2WI texture analysis model based on a node-by-node comparison for improving the diagnostic accuracy of lymph node metastasis (LNM) in rectal cancer. METHODS: A total of 381 histopathologically confirmed lymph nodes (LNs) were collected. LNs texture features were extracted from MRI-T2WI. Spearman's rank correlation coefficient and the least absolute shrinkage and selection operator were used for feature selection to construct the LN rad-score. Then the clinical risk factors and LN texture features were combined to establish combined predictive model. Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Decision curve analysis (DCA) and nomogram were used to evaluate the clinical application of the model. RESULTS: A total of 107 texture features were extracted from LN-MRI images. After selection and dimensionality reduction, the radiomics prediction model consisting of 8 texture features showed well-predictive performance in the training and validation cohorts (AUC, 0.676; 95% CI 0.582-0.771) (AUC, 0.774; 95% CI 0.648-0.899). A clinical-radiomics prediction model with the best performance was created by combining clinical and radiomics features, 0.818 (95% CI 0.742-0.893) for the training and 0.922 (95% CI 0.863-0.980) for the validation cohort. The LN Rad-score in clinical-radiomics nomogram obtained the highest classification contribution and was well calibrated. DCA demonstrated the superiority of the clinical-radiomics model. CONCLUSION: The lymph node T2WI-based texture features can help to improve the preoperative prediction of LNM.
Assuntos
Metástase Linfática , Imageamento por Ressonância Magnética , Neoplasias Retais , Humanos , Metástase Linfática/diagnóstico por imagem , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos , Valor Preditivo dos Testes , Idoso , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Nomogramas , Adulto , Interpretação de Imagem Assistida por Computador/métodosRESUMO
This study aimed to compare the detection rates of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer. A systematic search of major medical databases was conducted to identify studies up to September 2023. The primary outcome assessed was the detection rate of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in the primary tumor. Pooled risk ratios with a 95% CI were calculated using random-effect models to adjust for heterogeneity. Eight studies were included in the meta-analysis. 68Ga-FAPI-04 PET/CT has higher uptakes in lymph nodes, bone, and peritoneal metastasis compared with 18F-FDG PET/CT. The detection rate of 68Ga-FAPI-04 PET/CT based on lesion was better for lymph node metastasis (RR = 0.63, 95% CI 0.47-0.84, P = 0.002) and peritoneal metastasis (RR = 0.52, 95% CI 0.32-0.85, P = 0.009), both imaging modalities had essentially the same diagnostic efficacy in primary tumor (RR = 0.99, 95% CI 0.96-1.02, P = 0.49). 68Ga-FAPI-04 as a highly promising PET/CT tracer was superior to 18F-FDG PET/CT in colorectal cancer, especially in detecting lymph node metastases and peritoneal metastases.