A Novel Approach for Multiple Material Extrusion in Arthroscopic Knee Surgery.

Articular cartilage defects and degenerative diseases are pathological conditions that cause pain and the progressive loss of joint functionalities. The most severe cases are treated through partial or complete joint replacement with prostheses, even if the interest in cartilage regeneration and re-growth methods is steadily increasing. These methods consist of the targeted deposition of biomaterials. Only a few tools have been developed so far for performing these procedures in a minimally invasive way. This work presents an innovative device for the direct deposition of multiple biomaterials in an arthroscopic scenario. The tool is easily handleable and allows the extrusion of three different materials simultaneously. It is also equipped with a flexible tip to reach remote areas of the damaged cartilage. Three channels are arranged coaxially and a spring-based dip-coating approach allows the fabrication and assembly of a bendable polymeric tip. Experimental tests were performed to characterize the tip, showing the ability to bend it up to 90° (using a force of ~ 1.5 N) and to extrude three coaxial biomaterials at the same time with both tip straight and tip fully bent. Rheometric analysis and fluid-dynamic computational simulations were performed to analyze the fluids' behavior; the maximum shear stresses were observed in correspondence to the distal tip and the channel convergence chamber, but with values up to ~ 1.2 kPa, compatible with a safe extrusion of biomaterials, even laden with cells. The cells viability was assessed after the extrusion with Live/Dead assay, confirming the safety of the extrusion procedures. Finally, the tool was tested arthroscopically in a cadaveric knee, demonstrating its ability to deliver the biomaterial in different areas, even ones that are typically hard-to-reach with traditional tools.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial.

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.