Antibacterial‐nanocomposite bone filler based on silver nanoparticles and polysaccharides

Injectable bone fillers represent an attractive strategy for the treatment of bone defects. These injectable materials should be biocompatible, capable of supporting cell growth and possibly able to exert antibacterial effects. In this work, nanocomposite microbeads based on alginate, chitlac, hydroxyapatite and silver nanoparticles were prepared and characterized. The dried microbeads displayed a rapid swelling in contact with simulated body fluid and maintained their integrity for more than 30 days. The evaluation of silver leakage from the microbeads showed that the antibacterial metal is slowly released in saline solution, with less than 6% of silver released after 1 week. Antibacterial tests proved that the microbeads displayed bactericidal effects toward Staphylococcus aureus, Pseudomonas aeruginosa and Staphylococcus epidermidis, and were also able to damage pre‐formed bacterial biofilms. On the other hand, the microbeads did not exert any cytotoxic effect towards osteoblast‐like cells. After characterization of the microbeads bioactivity, a possible means to embed them in a fluid medium was explored in order to obtain an injectable paste. Upon suspension of the particles in alginate solution or alginate/hyaluronic acid mixtures, a homogenous and time‐stable paste was obtained. Mechanical tests enabled to quantify the extrusion forces from surgical syringes, pointing out the proper injectability of the material. This novel antibacterial bone filler appears as a promising material for the treatment of bone defects, in particular when possible infections could compromise the bone‐healing process. Copyright © 2016 John Wiley & Sons, Ltd.     

Nonunion fracture healing: Evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model

Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (a) develop a new large animal model for bone atrophic nonunion and (b) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a noncritical, full‐thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM + MSC) for 1 day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic, and histomorphometric analysis showed the formation of bone callus in DBM group, whereas the fracture healing appeared at an early stage in DBM + MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM + MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, whereas MSC do not improve the healing process when cultivated on DBM particles before implantation.     

Synchronous colorectal cancer using CT colonography vs. other means: a systematic review and meta-analysis

Objectives

The objective of our study was to systematically review the evidence about synchronous colorectal cancer diagnosed with or without computed tomography colonography (CTC).

Materials and methods

Two systematic searches were performed (PubMed and EMBASE) for studies reporting the prevalence of synchronous colorectal cancer (CRC): one considering patients who underwent CTC and the another one considering patients who did not undergo CTC. A three-level analysis was performed to determine the prevalence of patients with synchronous CRC in both groups of studies. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% confidence interval (CI) were calculated. A quality assessment (STROBE) was done for the studies.

Results

For CTC studies, among 2645 articles initially found, 21 including 1673 patients, published from 1997 to 2018, met the inclusion criteria. For non-CTC studies, among 6192 articles initially found, 27 including 111,873 patients published from 1974 to 2015 met the inclusion criteria. The pooled synchronous CRC prevalence was 5.7% (95% CI 4.7%–7.1%) for CTC studies, and 3.9% (95% CI 3.3%–4.4%) for non-CTC studies, with a significant difference (p = 0.004). A low heterogeneity was found for the CTC group (I² = 10.3%), whereas a high heterogeneity was found in the non-CTC group of studies (I² = 93.5%), and no significant explanatory variables were found. Of the 22 STROBE items, a mean of 18 (82%) was fulfilled by CTC studies, and a mean of 16 (73%) by non-CTC studies.

Conclusions

The prevalence of synchronous CRC was about 4–6%. The introduction of CTC is associated with a significant increase of the prevalence of synchronous CRCs.

     

Quantitative assessment of the effects of 6 months of adapted physical activity on gait in people with multiple sclerosis: a randomized controlled trial

Purpose: The purpose of this study is to quantitatively assess the effect of 6 months of supervised adapted physical activity (APA i.e. physical activity designed for people with special needs) on spatio-temporal and kinematic parameters of gait in persons with Multiple Sclerosis (pwMS).

Methods: Twenty-two pwMS with Expanded Disability Status Scale scores ranging from 1.5 to 5.5 were randomly assigned either to the intervention group (APA, n?=?11) or the control group (CG, n?=?11). The former underwent 6 months of APA consisting of 3 weekly 60-min sessions of aerobic and strength training, while CG participants were engaged in no structured PA program. Gait patterns were analyzed before and after the training using three-dimensional gait analysis by calculating spatio-temporal parameters and concise indexes of gait kinematics (Gait Profile Score – GPS and Gait Variable Score – GVS) as well as dynamic Range of Motion (ROM) of hip, knee, and ankle joints.

Results: The training originated significant improvements in stride length, gait speed and cadence in the APA group, while GPS and GVS scores remained practically unchanged. A trend of improvement was also observed as regard the dynamic ROM of hip, knee, and ankle joints. No significant changes were observed in the CG for any of the parameters considered.

Conclusions: The quantitative analysis of gait supplied mixed evidence about the actual impact of 6 months of APA on pwMS. Although some improvements have been observed, the substantial constancy of kinematic patterns of gait suggests that the full transferability of the administered training on the ambulation function may require more specific exercises.

• Implications for rehabilitation

• Adapted Physical Activity (APA) is effective in improving spatio-temporal parameters of gait, but not kinematics, in people with multiple sclerosis.

• Dynamic range of motion during gait is increased after APA.

• The full transferability of APA on the ambulation function may require specific exercises rather than generic lower limbs strength/flexibility training.

     

A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease.

AIMS: The role of aspirin in patients with coronary artery disease (CAD) is well established, yet patients happen to discontinue aspirin according to physician's advice or unsupervised. We thus undertook a systematic review to appraise the hazards inherent to aspirin withdrawal or non-compliance in subjects at risk for or with CAD. METHODS AND RESULTS: Electronic databases were systematically searched (updated January 2006). Study designs, patient characteristics, and outcomes were abstracted. Pooled estimates for odds ratios (OR) were computed according to random-effect methods. From the 612 screened studies, six were selected (50,279 patients). One study (31,750 patients) focused on adherence to aspirin therapy in the secondary prevention of CAD, two studies (2594) on aspirin discontinuation in acute CAD, two studies (13,706) on adherence to aspirin therapy before or shortly after coronary artery bypass grafting, and another (2229) on aspirin discontinuation among patients undergoing drug-eluting stenting. Overall, aspirin non-adherence/withdrawal was associated with three-fold higher risk of major adverse cardiac events (OR=3.14 [1.75-5.61], P=0.0001). This risk was magnified in patients with intracoronary stents, as discontinuation of antiplatelet treatment was associated with an even higher risk of adverse events (OR=89.78 [29.90-269.60]). CONCLUSION: Non-compliance or withdrawal of aspirin treatment has ominous prognostic implication in subjects with or at moderate-to-high risk for CAD. Aspirin discontinuation in such patients should be advocated only when bleeding risk clearly overwhelms that of atherothrombotic events.     

Extracorporeal membrane oxygenation and lethal diseases: A new perspective

Lethal cancer and chronic untreatable viral disease with life threatening consequences are among the major burden for morbidity and mortality in the western world. A large number of resources are employed every year in identification of new drugs to treat this condition. A remarkable percentage of resources are wasted for safety concerns about possible acute cardiac or pulmonary toxicity of the new identified compounds, that are rejected without further development even when promising. ExtraCorporeal Membrane Oxygenation (ECMO) is an established technique to support and replace cardio-pulmonary function that underwent rapid technologic improvement in the last years, resulting in reduced complication rate. ECMO has been used with success to treat acute life-threatening cardiac and pulmonary toxicity. Our hypothesis is that the new ECMO technological improvement could make this technique available to other setting, such as lethal cancer and infectious diseases, where it can provide a safe base to overwhelm acute cardiac and pulmonary toxicity of chemotoxic drugs and techniques. New drugs and old promising compounds rejected for toxicity could thus be re-introduced and employed, opening a new scenario in the treatment of life-threatening diseases.