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Severe bone fractures are often treated by appending internal fixations. In unhealthy or osteoporotic patients, post-implantation bone fractures can occur due to external impact (e.g. from a fall), day-to-day activities in highly-osteoporotic cases and mismatches in the stiffness of bone and the implant's biomaterial, since this causes stress concentrations. One approach to alleviating this problem is to use biomaterials that closely mimic the effective stiffness of real bone, thereby more seamlessly integrating the fixation. This requires to know the properties target (bone properties) and therefore, it highlights the relevance of the evaluation of the bone's mechanical properties which is impractical via direct measurement. This work presents a methodology (multistage homogenisation) for predicting the anisotropic stiffness of bone given the porosity and mineral fraction, both of which are more readily obtained than the mechanical properties themselves. Unlike previous work we: (i) account for finger-like morphology of the mineral phase at the nanoscale; (ii) use microscopy data to model the osteon geometry and its curvilinear anisotropy at the microscale, and (iii) use data to define the trabecular (microCT) and cortical (microscopy) bone geometries at the mesoscale. The predicts have been shown to agree favourably with experimental data in the literature as well as previous modelling works. The results are summarised in a database containing anisotropic stiffness tensors applicable to a broad range of degrees of bone health (e.g. mineral fractions and mesoscale porosities); thus, this work is a contribution towards being able to design more robust patient-specific bone implants in practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Tissue engineering combine biomaterials, cells and biologically active molecules having as a goal create functional tissues; many of the compositions are blends of a polymeric matrix with ceramic fillers, however, reduction of mechanical resistance can be a drawback on ceramic-polymer systems. In this manuscript, we investigate the potential of calcium-deficient hydroxyapatite (CDHA) whiskers, a needle shape bioceramic, to enhance mechanical and osteoconduction properties on the polymeric matrix. For this purpose, PCL scaffolds incorporating CDHA whiskers were produced by combining solvent casting and particulate leaching techniques to develop a composite scaffold that possess mechanical and biological properties which is useful for bone tissue engineering regeneration. We produced CDHA whiskers using alkaline hydrolysis of α-tricalcium phosphate and characterized by XRD, XRF and SEM. PCL/CDHA scaffolds were fabricated with a final porosity of ~70%, quantified by SEM images. Mechanical properties were evaluated by compression test. As an initial test, PCL/CDHA scaffolds were immersed in simulated body fluid to quantify apatite deposition. In vitro and in vivo studies were performed to assess cytotoxicity and bioactivity. CDHA whiskers exhibited a needle-like morphology and a Ca/P ratio equal to calcium deficient hydroxyapatite. The composite scaffolds contained interconnected pores 177 to 350 μm in size and homogeneous ceramic distribution. The addition of CDHA whiskers influences the mechanical results: higher elastic modulus and compressive strength was observed on PCL/CDHA samples. In vitro results demonstrated biocompatibility on PCL and PCL/CDHA films. In vivo data demonstrated cellular infiltration from the surrounding tissue with new bone formation that suggests bioactive potential of CDHA whiskers. Our goal was to produce a scaffold with a potential induction factor and a favorable morphology, which was proved according to this study's findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Data on survival and safety of sorafenib for hepatocellular carcinoma recurrence after liver transplant are still equivocal., Aim: We performed a meta-analysis of published studies, with the aim of estimating the 1-year rates of survival, analysing the variability in survival rates and, finally, identifying the factors associated with a longer survival., Methods: Data from 8 of the 17 selected studies were pooled, while the other 9 were excluded because survival rates were missing. All included studies were retrospective., Results: Overall, the 1-year survival ranged from 18% to 90%. Tumour progression was the main cause of death. The second cause was bleeding, reported only in patients undergoing m-Tor inhibitor therapy. The pooled estimate of 1-year survival was 63%. There was a significant heterogeneity among studies (P < 0.0001). Among the 34 variables assessed by univariate meta-regression, 5 were associated with an increase in the 1-year survival rate: (1) male gender (P = 0.001); (2) Time to progression (P = 0.038); and adverse drug events, divided in (3) gastrointestinal (P = 0.038), (4) cardiovascular (P = 0.029), and (5) dermatological (P = 0.014)., Conclusions: Additional data from multicentre prospective studies are required to clearly determine if sorafenib is a safe and acceptable treatment in hepatocellular carcinoma recurrence after liver transplant. Nevertheless, its association with m-Tor inhibitors should be discouraged., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5alpha-reductase type II (SRD5A2), cytochrome P450c17alpha (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease., Methods: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category., Results: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2%, odds ratio (OR): 2.29, P: 0.05). Females mostly contributed to this association (OR: 4.95, P: 0.01) and OR values increased in post-menopausal women (OR: 6.00, P: 0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms., Conclusions: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.

Background/aims: Recent studies have suggested that the course of chronic hepatitis C may be influenced by the immunogenetic background of the host. Specifically, HLA-DR11 (5) has been associated with less advanced hepatitis C virus (HCV)-related liver disease. The aim of the present study was to investigate whether HLA-DRB1*11 subtypes or HLA-DQA1 and DQB1 genes might be associated with protection from or susceptibility to chronic HCV infection, histological severity of HCV-induced liver disease and infecting HCV genotype., Methods: Ninety-nine unrelated outpatients with histologically documented chronic hepatitis C were studied and their allele frequencies were compared with those of 179 ethnically matched controls and with those of 41 HCV RNA-positive patients with persistently normal aminotransferase levels (HCV carriers). HLA-DQ types and HLA-DRB1*11 subtypes were determined by polymerase chain reaction gene amplification with sequence specific primers., Results: None of 10 DQA1 or 12 DQB1 alleles was significantly associated with susceptibility to or protection from chronic HCV infection or with histological staging or with HCV genotype. However, analysis of DQA1-DQB1 combinations showed that DQA1*0201-DQB1*0201 combination was significantly more frequent in patients compared to controls, both in cis (26.3% vs 16.2%, p = 0.04, odds ratio = 1.8, 95% confidence interval, 0.96-3.5) and in trans (12.1% vs. 1.1%, p = 0.0001, OR = 12.2, 95% CI, 2.6-113.7). HCV carriers did not differ from controls or from patients in the frequency of DQA1-DQB1 combinations. The extended haplotype DRB1*1104, DQA1*0501, DQB1*0301 was seen significantly less frequently in patients than in controls (8% vs 22.3%, p = 0.0025, OR = 0.31, 95% CI, 0.12-0.7) or HCV-RNA carriers (8% vs 26.8%, p = 0.003, OR = 0.24, 95% CI, 0.08-0.73)., Conclusions: Immunogenetic factors may play a role in determining both protection from and susceptibility to chronic hepatitis C, the trans-dimer DQA1*0201-DQB1*0201 predisposing to and the DRB1*1104, DQA1*0501, DQB1*0301 haplotype protecting from chronic hepatitis C.

Aims: We aimed to test the hypothesis that susceptibility to chronic HBV, HDV and HCV infections or their pathology is influenced by host genetic factors., Methods: The Human Leukocyte Antigens (HLA) (A, B, DR and DQ) were determined by microlymphocytotoxicity assay in patients with chronic C (n = 117), B (n = 97) or D (n = 27) hepatitis and their frequencies were compared with those of 489 healthy controls., Results: No statistically significant association was found between any HLA antigen and chronic B or D hepatitis. A significantly higher frequency of HLA-B14 was observed in patients with chronic persistent or active C hepatitis (16.7% of 90 versus 5.9% of 489, chi(2) = 10.9, pc < 0.05, Relative Risk = 3.17, Etiological Fraction = 0.11). The frequency of HLA-DR5 was lower in HCV positive patients (24.8%) than in controls (45%, chi(2) = 15.1, pc < 0.005, RR = 0.4, EF = -0.37)., Conclusions: No correlation could be observed between clearance of HBV or HDV and HLA phenotype. Immunogenetic factors may have a role in determining susceptibility to chronic HCV hepatitis, and in Italian patients HLA-DR5 is a protective factor.