Zoledronic acid improves bone quality and muscle function in a high bone turnover state.

SUMMARY: Zoledronic acid (ZA) prevents muscle weakness in mice with bone metastases; however, its role in muscle weakness in non-tumor-associated metabolic bone diseases and as an effective treatment modality for the prevention of muscle weakness associated with bone disorders, is unknown. We demonstrate the role of ZA-treatment on bone and muscle using a mouse model of accelerated bone remodeling, which represents the clinical manifestation of non-tumor associated metabolic bone disease. ZA increased bone mass and strength and rescued osteocyte lacunocanalicular organization. Short-term ZA treatment increased muscle mass, whereas prolonged, preventive treatment improved muscle mass and function. In these mice, muscle fiber-type shifted from oxidative to glycolytic and ZA restored normal muscle fiber distribution. By blocking TGFß release from bone, ZA improved muscle function, promoted myoblast differentiation and stabilized Ryanodine Receptor-1 calcium channel. These data demonstrate the beneficial effects of ZA in maintaining bone health and preserving muscle mass and function in a model of metabolic bone disease. Context and significance: TGFß is a bone regulatory molecule which is stored in bone matrix, released during bone remodeling, and must be maintained at an optimal level for the good health of the bone. Excess TGFß causes several bone disorders and skeletal muscle weakness. Reducing excess TGFß release from bone using zoledronic acid in mice not only improved bone volume and strength but also increased muscle mass, and muscle function. Progressive muscle weakness coexists with bone disorders, decreasing quality of life and increasing morbidity and mortality. Currently, there is a critical need for treatments improving muscle mass and function in patients with debilitating weakness. Zoledronic acid's benefit extends beyond bone and could also be useful in treating muscle weakness associated with bone disorders.

Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation.

Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel.

Outcome of Laparoscopic Assisted Percutaneous Microwave Ablation for Exophytic Versus Non-exophytic Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies and is the third cause of cancer-related death worldwide. Surgery is the optimal treatment for early HCC; however, the majority of cases are not suitable for curative resection at the time of diagnosis. Surgical resection difficulties may be related to size, site, number of tumors, extrahepatic involvement, and patient general condition. Exophytic tumors were considered as relative contraindication for thermal ablation because of the risk of incomplete ablation or major complications as hemorrhage and seeding. AIM OF THIS STUDY: to evaluate the safety and efficacy of microwave ablation (MWA) of exophytic HCC in comparison with non-exophytic HCC. METHODS: Prospective comparative study carried on 30 patients having 30 exophytic (six of those patients had another non-exophytic lesion) and 32 patients having 44 non-exophytic HCC lesions (22 had single lesion, 8 patients had 2 lesions, and 2 patients had 3 lesions) within Milan criteria. All patients were child A or B, they were subjected to full clinical assessment, laboratory investigations, and radiological investigations. Laparoscopic assisted percutaneous MWA was the procedure of choice in our study for all patients either having exophytic or non-exophytic lesions using no-touch wedge technique for exophytic lesions and direct puncture for non-exophytic lesions. RESULTS: Technical success was 100% in both groups, all lesions were completely ablated as confirmed by LIOUS. There were no major complications or perioperative mortality and low incidence of local tumor progression in both exophytic and non-exophytic groups. CONCLUSION: Laparoscopic assisted MWA of exophytic HCC is safe and effective with comparable results to non-exophytic HCC. Exophytic HCC is not contraindication for MWA with proper technique selection.