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Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA. Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values (P FDR). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses. Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052-1.156, P FDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, P FDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, P FDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, P FDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (ß = -0.258, 95% CI = -0.369 to 0.146, P FDR = 0.6.07E-06), grip strength (left, ß = -0.064, 95% CI = -0.104 to 0.024, P FDR = 0.002; right, ß = -0.055, 95% CI = -0.095 to 0.014, P FDR = 0.008), and usual walking pace (ß = -0.104, 95% CI = -0.147 to 0.061, P FDR = 1.61E-05). Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP.
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AIM: To evaluate the impact of glycemic control and nutritional status after total pancreatectomy (TP) on complications, tumor recurrence and overall survival. METHODS: Retrospective records of 52 patients with pancreatic tumors who underwent TP were collected from 2007 to 2015. A series of clinical parameters collected before and after surgery, and during the follow-up were evaluated. The associations of glycemic control and nutritional status with complications, tumor recurrence and long-term survival were determined. Risk factors for postoperative glycemic control and nutritional status were identified. RESULTS: High early postoperative fasting blood glucose (FBG) levels (OR = 4.074, 95%CI: 1.188-13.965, P = 0.025) and low early postoperative prealbumin levels (OR = 3.816, 95%CI: 1.110-13.122, P = 0.034) were significantly associated with complications after TP. Postoperative HbA1c levels over 7% (HR = 2.655, 95%CI: 1.299-5.425, P = 0.007) were identified as one of the independent risk factors for tumor recurrence. Patients with postoperative HbA1c levels over 7% had much poorer overall survival than those with HbA1c levels less than 7% (9.3 mo vs 27.6 mo, HR = 3.212, 95%CI: 1.147-8.999, P = 0.026). Patients with long-term diabetes mellitus (HR = 15.019, 95%CI: 1.278-176.211, P = 0.031) and alcohol history (B = 1.985, SE = 0.860, P = 0.025) tended to have poor glycemic control and lower body mass index levels after TP, respectively. CONCLUSION: At least 3 mo are required after TP to adapt to diabetes and recover nutritional status. Glycemic control appears to have more influence over nutritional status on long-term outcomes after TP. Improvement in glycemic control and nutritional status after TP is important to prevent early complications and tumor recurrence, and improve survival.
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Glucemia/análisis , Recurrencia Local de Neoplasia/prevención & control , Estado Nutricional , Pancreatectomía/efectos adversos , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/prevención & control , Anciano , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Supervivencia sin Enfermedad , Ayuno , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Pancreáticas/sangre , Complicaciones Posoperatorias/epidemiología , Periodo Posoperatorio , Prealbúmina/análisis , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIM: To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma (PDAC) and assess unresectability of synchronous liver metastasis. METHODS: Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group. RESULTS: CA125 > 38 U/mL (OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus (OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL (OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years (OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with post-operatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels (7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone (7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula (P = 0.072) or other complications (P = 0.230) and no greater impacts on length of hospital stay (P = 0.602) or post-operative diabetic control (P = 0.479). CONCLUSION: The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.
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Carcinoma Ductal Pancreático/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Metastasectomía , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Factores de Edad , Anciano , Antígeno Ca-125/sangre , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/secundario , China/epidemiología , Bases de Datos Factuales , Diabetes Mellitus/epidemiología , Femenino , Humanos , Complicaciones Intraoperatorias/epidemiología , Estimación de Kaplan-Meier , Tiempo de Internación , Neoplasias Hepáticas/secundario , Modelos Logísticos , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Fístula Pancreática/epidemiología , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/patología , Complicaciones Posoperatorias/epidemiología , Periodo Preoperatorio , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVE: to observe the association between myocardial fibrosis, detected by delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) and arrhythmia in patients with hypertrophic cardiomyopathy (HCM). METHODS: forty-eight untreated HCM patients who underwent Cine MR, DE-MRI, 24 h ambulatory Holter electrocardiogram and ECG examinations were recruited. Extent of myocardial fibrosis (fibrosis mass/total LV mass) was assessed using DE imaging. Association between arrhythmias including premature ventricular complexes (PVCS ≥ 200), supra-ventricular tachycardia (SVT), non-sustained ventricular tachycardia (NSVT), atrio-ventricular block (AVB) and intra-ventricular block (IVB) detected by Holter monitoring and ECG with regard to delayed enhancement (DE) on contrast enhanced CMR was analyzed. RESULTS: myocardial fibrosis was detected in 35 patients. Incidence of arrhythmia was significantly higher in patients with DE than in patients without DE (P < 0.05). Extent of myocardial fibrosis was significantly associated with the QRS duration (r = 0.33, P < 0.001). CONCLUSION: myocardial fibrosis detected by DE-CMR was associated with arrhythmia in patients with HCM. DE-CMR might be helpful to detect high-risk HCM patients prone to arrhythmia.
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Arritmias Cardíacas/etiología , Cardiomiopatía Hipertrófica/patología , Cardiomiopatía Hipertrófica/fisiopatología , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Cardiomiopatía Hipertrófica/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To explore the effect of hypoxia inducible factor-1 alpha (HIF-1 alpha) gene on the expression of vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (hRPE) cells under hypoxia conditions by using small hairpin loop RNA (shRNA) to silence HIF-1 alpha. METHODS: CoCl(2) (150 micromol/L) was used to simulate the hypoxia environment for hRPE cells. After choosing a target site of HIF-1 alpha mRNA, shRNA was designed and synthesized by this target site. hRPE cells were transfected by this shRNA in vitro. Then, these cells were cultured under hypoxia conditions (150 micromol/L CoCl(2)). The mRNA expression of HIF-1 alpha and VEGF was measured by semi-quantitative reverse transcription PCR (RT-PCR). The protein level of HIF-1 alpha and VEGF was studied by western blot analysis. RESULTS: After hRPE cells were transfected by HIF-1 alpha-specific shRNA, RT-PCR showed that the expression of HIF-1 alpha mRNA was inhibited by 77.1%, and western blot analysis showed that the level of HIF-1 alpha protein was significantly decreased in hRPE cells under hypoxia conditions. Moreover, the expression of VEGF mRNA was inhibited by 27.8% and the level of VEGF protein was also significantly decreased in transfected hRPE cells under hypoxia conditions. CONCLUSIONS: Under hypoxia conditions, HIF-1 alpha-specific shRNA effectively keeps HIF-1 alpha gene silenced, and consequently down-regulates VEGF expression against hypoxia. These results suggest that HIF-1 alpha is one of the most important cytokines for retinal neovascularization.