RESUMEN
The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) is increasing annually. The prognostic nutritional index (PNI) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. This study aimed to identify the short-term prognostic value of preoperative PNI in elderly patients who underwent neurosurgical clipping for aSAH. This retrospective study included elderly patients with aSAH who underwent neurosurgical clipping from January 2018 to December 2020. Clinical variables and 6-month outcomes were collected and compared. Epidemiological data and effect factors of prognosis were evaluated. Multivariate logistic regression and receiver operating characteristics (ROC) curve analyses were used to evaluate the predictive value of preoperative PNI. Multiple logistic regression was performed to establish a nomogram. A total of 124 elderly patients were enrolled. Multivariate logistic regression analysis showed that preoperative PNI (odds ratio (OR), 0.779; 95% confidence interval (CI), 0.689-0.881; P < 0.001), Hunt-Hess grade (OR, 3.291; 95%CI, 1.816-5.966; P < 0.001), and hydrocephalus (OR, 9.423; 95%CI, 2.696-32.935; P < 0.001) were significant predictors. The area under the ROC curve of PNI was 0.829 (95% CI, 0.755-0.903; P < 0.001) with a sensitivity and specificity of 68.4% and 83.3%, respectively, and the cutoff value was 46.36. Patients with preoperative PNI of < 46.36 had a significantly unfavorable 6-months prognosis (F = 40.768, P < 0.001). Preoperative PNI is independently correlated with the 6-month prognosis in elderly patients who undergo neurosurgical clipping for aSAH.
Asunto(s)
Hemorragia Subaracnoidea , Humanos , Anciano , Pronóstico , Hemorragia Subaracnoidea/cirugía , Evaluación Nutricional , Estudios Retrospectivos , NomogramasRESUMEN
Chondroblastoma (CBL) is a benign bone tumor occurring mostly in teenagers. Despite this, CBL can recur and metastasize after curettage, which may impede normal epiphysis. In search of a novel targeted therapy for CBL, we aimed at BMP-2, a factor critical for chondro-osteogenesis and chondrocyte proliferation. Two pathways upstream of BMP-2, the mTOR and HIF, were targeted with rapamycin (Rapa) and FM19G11 (FM), respectively. Using immunohistochemistry, we found BMP-2 was highly expressed in CBL tissues. CBL cells explanted and confirmed with higher BMP-2 level than normal cartilage. Protumorigenic effect of Rapa and FM on CBL cells were transduced via BMP-2. Combination of Rapa and FM conferred stronger inhibition of cell proliferation than either monotherapy and inhibited levels of chondro-osteogenic markers (Sox9, aggrecan, and type II collagen). To minimize the adverse effect of Rapa, we performed screening in essential amino acids and found leucine deprivation-sensitized CBL cells to Rapa. Combination treatment of low dose Rapa, FM, and leucine deprivation conferred compatible inhibitory effects on CBL cell proliferation, chondro-osteogenic potential, and tumorigenic capacity. We conclude that targeting BMP-2 using mTOR/HIF inhibition could potently curb the disease. Addition of low-leucine diet could lower the dose of rapamycin in chase for less toxicity.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Benzamidas/farmacología , Proliferación Celular/efectos de los fármacos , Condroblastoma/tratamiento farmacológico , Sirolimus/farmacología , Adolescente , Adulto , Proteína Morfogenética Ósea 2/genética , Proteína Morfogenética Ósea 2/metabolismo , Condrogénesis/efectos de los fármacos , Regulación hacia Abajo , Femenino , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Factor 1 Inducible por Hipoxia/metabolismo , Leucina/metabolismo , Masculino , Osteogénesis/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Técnicas de Cultivo de Tejidos , Células Tumorales Cultivadas/efectos de los fármacos , Adulto JovenRESUMEN
We have investigated the role of bone-morphogenetic protein (BMP) 2 and tumor necrosis factor α (TNF-α) in 33 patients with bladder cancer (BCa) with bone metastasis. Thirty nonmetastatic BCas were included as controls. Immunohistochemical staining with BMP-2 and TNF-α was performed. Expressions of the factors were quantified and studied statistically. As a result, a trend showing higher expression of BMP-2 and TNF-α was associated with advanced disease. Expressions of BMP-2 and TNF-α were significantly higher in BCa with bone metastases (P = .0002 and P = .0172, respectively). The expression of BMP-2 and TNF-α showed a direct correlation in metastatic and muscle-invasive cases (P = .0202 and P = .0004, respectively) but not in nonmetastatic or noninvasive BCa (P = .1834 and P = .9215, respectively). It is postulated that BMP-2 can be responsible for the mechanism involved in triggering bone metastasis in BCa. The correlation with TNF-α indicates that the interaction of the 2 factors may promote local invasion and distant metastasis, especially to bone.
Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Neoplasias Óseas/secundario , Carcinoma de Células Transicionales/secundario , Factor de Necrosis Tumoral alfa/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/metabolismo , Carcinoma de Células Transicionales/metabolismo , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
OBJECTIVE: To study whether the rates of pregnancy and implantation decline in repeated IVF/ICSI cycles and whether the decline is associated with the availability of embryo cryopreservation. METHODS: We retrospectively analyzed the pregnancy and implantation rates of 1,033 IVF/ICSI cycles accomplished in our center to determine the association of the clinical outcomes with the availability of embryo cryopreservation. RESULTS: The rates of pregnancy and implantation declined slightly in the cycles with embryo cryopreservation (43% vs 43%, P > 0.05; 29% vs 24% , P > 0.05), but significantly in the repeated IVF/ICSI cycles without embryo cryopreservation (43% vs 35%, 43% vs 22% , P < 0.05; 29% vs 23% , 29% vs 16% , P < 0.05). CONCLUSION: The rates of pregnancy and implantation remain similar in the following cycles for those with embryo cryopreservation in the first IVF/ICSI cycles, but decline significantly in the repeated IVF/ICSI cycles for those without.