Circulating miR-26b-5p and miR-451a as diagnostic biomarkers in medullary thyroid carcinoma patients.

PURPOSE/METHODS: The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated. RESULTS: The samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients. CONCLUSION: This study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine.

Culture of 3D bioprinted bone constructs requires an increased fluid dynamic stimulation.

In vitro flow-induced mechanical stimulation of developing bone tissue constructs has been shown to favor mineral deposition in scaffolds seeded with cells directly exposed to the fluid flow. However, the effect of fluid dynamic parameters, such as shear stress (SS), within 3D bioprinted constructs is still unclear. Thus, this study aimed at correlating the SS levels and the mineral deposition in 3D bioprinted constructs, evaluating the possible dampening effect of the hydrogel. Human mesenchymal stem cells (hMSCs) were embedded in 3D bioprinted porous structures made of alginate and gelatin. 3D bioprinted constructs were cultured in an osteogenic medium assessing the influence of different flow rates (0, 0.7 and 7 ml/min) on calcium and collagen deposition through histology, and bone volume (BV) through micro-computed tomography. Uniform distribution of calcium and collagen was observed in all groups. Nevertheless, BV significantly increased in perfused groups as compared to static control, ranging from 0.35±0.28 mm3, 11.90±8.74 mm3 and 25.81±5.02 mm3 at week 3 to 2.28±0.78 mm3, 22.55±2.45 mm3 and 46.05±5.95 mm3 at week 6 in static, 0.7 and 7 ml/min groups, respectively. SS values on construct fibers in the range 10-100 mPa in 7 ml/min samples were twice as high as those in 0.7 ml/min samples showing the same trend of BV. The obtained results suggest that it is necessary to enhance the flow-induced mechanical stimulation of cell-embedding hydrogels to increase the amount of mineral deposited by hMSCs, compared to what is generally reported for the development of in vitro bone constructs. STATEMENT OF SIGNIFICANCE: In this study, we evaluated for the first time how the hydrogel structure dampens the effect of flow-induced mechanical stimulation during the culture of 3D bioprinted bone tissue constructs. By combining computational and experimental techniques we demonstrated that those shear stress thresholds generally considered for culturing cells seeded on scaffold surface, are no longer applicable when cells are embedded in 3D bioprinted constructs. Significantly, more bone volume was formed in constructs exposed to shear stress values generally considered as detrimental than in constructs exposed shear stress values generally considered as beneficial after 3 weeks and 6 weeks of dynamic culture using a perfusion bioreactor.

Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies.

BACKGROUND: Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. AIM: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. RESULTS: A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. CONCLUSIONS: Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity.

Lesions of the sciatic nerve in fractures of the acetabulum.

Between 1982 and 1992 a total of 211 fractures of the acetabulum were operated. There was lesion of the sciatic nerve in 21 cases, the pathogenesis and evolution of which were studied. Clinical follow-up was obtained at least 2 years after occurrence of neurological deficit and supported in 13 cases by electromyography. Based on an analysis of the literature and of these series it is observed how spontaneous recovery of paralysis is not rare, even if it requires a long period of time. The presence of various levels of lesion, which are not easily diagnosed, and which are not easily attacked surgically, calls for a prudent attitude with regard to neurolysis.

Surgical treatment of both-column fractures by staged combined ilioinguinal and Kocher-Langenbeck approaches.

Between 1981 and 1989, 18 patients affected by both-column acetabular fractures were operated on by staged combined ilioinguinal and Kocher-Langenbeck approaches. Postoperative reduction quality and long-term radiographic results were evaluated according to the Matta radiological systems. The Harris hip scoring system was used for the functional results. Average follow-up was 53.2 months, ranging from 24 to 132 months. Reduction was anatomical in five cases (27.8 per cent), satisfactory in 11 (67.1 per cent), and non-anatomical in two cases (11.1 per cent). Radiographic long-term results were excellent in nine cases (50 per cent), good in five (27.8 per cent), fair in two (11.1 per cent) and poor in two (11.1 per cent). The Harris score was more than 90 in eight patients (44.4 per cent), between 80 and 90 in seven (38.8 per cent), between 80 and 70 in one (5.5 per cent), and less than 70 in two (11.1 per cent).

An experimental model to measure the torque of pin insertion and extraction for external fixation.

An original system used to measure torque of pin insertion and extraction in external fixation is presented. The system is made up of an electronic dynamometric key and an analogic/digital switchboard that may be linked up to a personal computer. The in vitro results show the simplicity of use and the versatility of the system, that is capable of providing the surgeon with accurate indicative values as to the mechanical resistance of the bone-pin interface during implantation of any fixator.

Composite bone grafting and plate fixation for the treatment of nonunions of the forearm with segmental bone loss: a report of eight cases.

Between June 1986 and December 1991, eight aseptic isolated severe forearm segmental bone losses were treated. The average age of the patients was 26 years. Three cases involved the radius and five the ulna. The average time between the onset of trauma and the final surgical intervention was 9 months. The surgical technique consisted of complete removal of necrotic bone, filling of the bone defect with an intercalary autogenous bone graft, and stable internal fixation, which required combining a plate and an opposite cortical bone allograft. The average bone loss length after freshening the bone ends was 7 cm (range 4-11). The average follow-up was 48 months (range 24-80). In all eight cases union and recovery of forearm function was achieved. The proposed surgical technique proved to be effective in obtaining results with no major complications.

Surgical treatment of bicondylar fractures of the distal humerus.

Between 1981 and 1989 22 bicondylar fractures of the distal humerus were operated on. Fractures were classified according to the AO system. Fixation consisted of medial and lateral plates combined to articular screws in 14 cases, one articular screw associated to one medial screw and a lateral plate in four cases, three lag screws in three cases, and in one case the articular screw was associated to one medial screw and one 'Y' plate. Osteotomy of the olecranon was fixed by one intramedullary screw and one wire in 15 cases, other simpler methods (wire or screw alone) were used in seven cases. A scoring system that included pain, range of motion, radiological results and postoperative activity level, was developed to study the results. Two fractures went to nonunion. Results were quoted as excellent in six cases, good in five cases, fair in eight patients and poor in three cases. Younger patients achieved a better range of motion (P = 0.039) and better functional level (P = 0.015), and differences in radiological score (P = 0.029), activity level score (P = 0.048) and total score (P = 0.0031) were observed depending on the anatomical fracture type.