Preclinical investigation of an innovative magnesium-based bone graft substitute for potential orthopaedic applications

SummaryDegradable or corrosive biometal is an attractive research and development (R&D) area in clinical orthopaedics. This study was designed to investigate biomechanical and biological properties of magnesium (Mg) and strontium (Sr) with a focus on Mg-based metals, including pure Mg and Mg–xwt% Sr (x = 0.25, x = 1.0, x = 1.5, x = 2.5) alloys, as potential bone graft substitutes in respect to their mechanical strength, corrosion resistance, and cytocompatibility for further optimization and establishing indications for relevant in vivo applications. Our data showed that the tensile and compressive strength increased with addition of Sr because of the Mg17Sr2 precipitation strengthen. Compared with commercially used bone graft substitutes, the mechanical properties of Mg–Sr alloys were close to those of cortical bone, and the compressive strength could reach 300 MPa, suggesting its potential application for load-bearing bone as bone defect filler. The corrosion rates of Mg–xwt% Sr alloys were controlled in the range of 0.05–0.07 mm/y, indicating feasibility of bone grafting and the in situ bone repair process. Moreover, Mg–Sr alloys also exhibit good cytocompatibility and antibacterial properties. Our innovation presented in this work supported in vivo clinical indication-based assessment of biodegradable Mg-based metals that could be potential candidates for bone graft substitutes for future orthopaedic applications

Liver Transplantation in an Adult with Citrullinaemia Type 2

Citrullinaemia is a urea cycle defect that results from a deficiency of the enzyme arginosuccinate synthetase. Type 1 disease is diagnosed in childhood, whereas Type 2 disease is adult onset. We report the outcome of a patient with citrullinemia Type 2 who received a liver transplant at our center and the implications of this diagnosis in liver transplantation

Cost-effective fabrication of bio-inspired nacre-like composite materials with high strength and toughness

A cost-effective one-step densification process based on bi-directional freeze casting was investigated to produce nacre-like alumina/poly (methyl methacrylate) (PMMA) composites with a unique micro-layered (μL) architecture. This method has the advantage of shorter processing time, as it requires only sintering once instead of twice as in the fabrication of conventional brick-and-mortar (BM) composites via freeze casting. By tuning the processing parameters, composites with different ceramic content and layer thickness were obtained. The resultant mechanical properties of μL composites showed that ceramic content and wall thickness affected mechanical properties significantly. The μL composite with fine ceramic walls (8 μm) and relatively high ceramic fraction (72 vol%) exhibited an exceptional combination of high flexural strength (178 MPa) and fracture toughness (12.5 MPa m1/2). The μL composites were also compared with the conventional BM composites. Although the fracture behaviour of both composites exhibited similar extrinsic toughening mechanisms, the μL composites with longer ceramic walls displayed superior mechanical properties in terms of strength and fracture toughness in comparison with the BM composites comprising short ceramic walls (i.e. bricks), due to the effectiveness of stress transfer of load-bearing ceramic phase within the composites

Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case–control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BC(OG)) and IVGTT (BC(IV)), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUC(GLP-1)). Per cent incretin effect was estimated as 100×(BC(OG)−BC(IV))/BC(OG)). RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BC(OG), p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUC(GLP-1) but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001). CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM. TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254

Surveillance of Broad-Spectrum Antibiotic Prescription in Singaporean Hospitals: A 5-Year Longitudinal Study

10.1371/journal.pone.0028751PLoS ONE612

First-line systemic treatment strategies for unresectable hepatocellular carcinoma: a cost-effectiveness analysis

Background Oral multikinase inhibitors and immune checkpoint inhibitors (ICIs) are effective for treating advanced hepatocellular carcinoma (aHCC) but may increase cost. This study compared the cost-effectiveness of oral multikinase inhibitors and ICIs in the first-line treatment of patients with aHCC. Methods A three-state Markov model was established to study the cost-effectiveness of drug treatment from the perspective of Chinese payers. The key outcomes in this study were total cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). Results The total costs and QALYs of sorafenib, sunitinib, donafenib, lenvatinib, sorafenib plus erlotinib, linifanib, brivanib, sintilimab plus IBI305, and atezolizumab plus bevacizumab were $9070 and 0.25,$9362 and 0.78, $33,814 and 0.45,$49,120 and 0.83, $63,064 and 0.81,$74,814 and 0.82, $81,995 and 0.82,$74083 and 0.85, and $104,188 and 0.84, respectively. The drug regimen with the lowest ICER was sunitinib ($551 per QALY), followed by lenvatinib ($68,869 per QALY). For oral multikinase inhibitors, the ICER of lenvatinib, sorafenib plus erlotinib, linifanib and brivanib compared with sunitinib was$779576, $1534,347,$1768,971, and $1963,064, respectively. For ICIs, sintilimab plus IBI305 is more cost effective than atezolizumab plus bevacizumab. The model was most sensitive to the price of sorafenib, the utility of PD, and the price of second-line drugs. Conclusion For oral multikinase inhibitors, the order of possible treatment options is sunitinib > lenvatinib > sorafenib plus erlotinib > linifanib > brivanib > donafenib. For ICIs, the order of possible treatment options is sintilimab plus IBI305 > atezolizumab plus bevacizumab