Prospective Multicenter Trial of Cervical Arthroplasty with the ROTAIO® Cervical Disc Prosthesis.

STUDY DESIGN Clinical observational study. OBJECTIVE The ROTAIO® cervical disc prosthesis is a novel unconstrained implant with a variable center of rotation aiming at physiological motion. The objective of this multicenter prospective trial was to evaluate clinical outcome and complications within 2 years. MATERIAL AND METHODS 120 patients (72 females and 48 males with median age of 43.0 years [23-60 yrs] underwent ACDA (ROTAIO®, SIGNUS Medical, Alzenau, Germany) and were prospectively followed for 24 months. Preoperative complaints were mainly associated with radiculopathy (n = 104) or myelopathy (n=16). There were 108 monosegmental and 12 bisegmental procedures including 6 hybrid constructs. Clinical outcome was evaluated at 3, 12 and 24 months in 100%, 96% and 77% of the cohort by VAS, NDI, WL-26, Patient`s Satisfaction Index (PSI), SF-36, Nurick Score, mJOA, Composite Success Rate, complications, patient`s overall satisfaction and analgesics use. RESULTS Highly significant clinical improvements were observed according to NDI and VAS (P < .0001 (arm); P < .001 (neck); P = .002 (head)) at all time points. Analgetic use could be reduced in 87.1 to 95.2%. Doctor`s visits have been reduced in 93.8% after 24 months. Patient`s overall satisfaction was high with 78.4 to 83.5% of patients. The composite success rate was 77.5% after 12 months and 76.9% after 24 months. There were no major complications in this series. Slight subsidence of the prosthesis was observed in 2 patients and 3 patients demonstrated fusion after 24 months. 2 patients developed symptomatic foraminal stenosis, so that implant removal and fusion was performed resulting in a revision rate of 1.7% in 2 years. CONCLUSION The ROTAIO® cervical disc prosthesis is a safe and efficient treatment option for symptomatic degenerative disc disease demonstrating highly significant clinical improvement and high patient`s overall satisfaction with very low revision rates at 2 years

Prospective Multicenter Trial of Cervical Arthroplasty With the ROTAIO® Cervical Disc Prosthesis

Objective Anterior Cervical Discectomy and Arthroplasty (ACDA) is an established treatment for degenerative cervical disc disease and seems to be an alternative to fusion in minimizing the risk of Adjacent Segment Disease (ASD). The ROTAIO® cervical disc prosthesis is a novel unconstrained implant with a variable center of rotation aiming at physiological motion. The objective of this multicenter prospective trial was to evaluate clinical outcome and complications within 2 years. Material and Methods 120 patients (72 females and 48 males with a median age of 43.0 years; range: 23 to 60 years) underwent ACDA (ROTAIO®, SIGNUS Medical, Alzenau, Germany) and were prospectively followed for 24 months. Preoperative complaints were mainly associated with radiculopathy (n=104) or myelopathy (n=16). There were 108 monosegmental and 12 bisegmental procedures including 6 hybrid constructs. Clinical outcome was evaluated at 3, 12 and 24 months by the Visual Analogue Scale (VAS) for head, neck and arm pain, the Neck Disability Index (NDI), the Work Limitation Questionnaire (WL-26), the Patient`s Satisfaction Index (PSI) and a Quality of Life Questionnaire (SF-36). The Nurick Score, the Modified Japanese Orthopaedic Association Score (mJOA) plus a Composite Success Rate have been additionally applied. Finally, complications, the patient`s overall satisfaction and the amount of analgesics were assessed. Results Highly significant clinical improvements were observed according to NDI and VAS (p<0.0001 (arm); p<0.001 (neck); p=0.002 (head)) at all postoperative time points. Analgetic medication could be reduced after 3 months in 91.3%, after 12 months in 87.1% and after 24 months in 95.2% of patients. Doctor`s visits for cervical spine problems have been reduced in 93.8% after 24 months. Patient`s overall satisfaction was high after 3, 12 and 24 months with 83.5%, 78.4% and 79.1% of patients, while 4.1%, 6.8% and 7.0% respectively were not satisfied. The composite success rate was 77.5% after 12 months and 76.9% after 24 months. There were no major complications in this series. Slight subsidence of the prosthesis was observed in 2 patients and 3 patients demonstrated fusion after 24 months. 2 patients developed symptomatic foraminal stenosis, so that implant removal and fusion was performed. Conclusion The ROTAIO® cervical disc prosthesis is a safe and efficient treatment option for symptomatic degenerative disc disease demonstrating excellent clinical results at 2 years. Outcome proves to be stable over time with very low revision rates

Analysis of the Substrate Specificity of the Dim-5 Histone Lysine Methyltransferase Using Peptide Arrays

Histone methylation is an epigenetic mark essential for gene regulation and development. We introduce peptide SPOT synthesis to study sequence specificity of the Dim-5 histone-3 lysine-9 methyltransferase. Dim-5 recognizes R8-G12 of the H3 tail with T11 and G12 being the most important specificity determinants. Exchange of H3 tail residue S10 and T11 by E strongly reduced methylation by Dim-5, suggesting that phosphorylation of S10 or T11 may regulate the activity of Dim-5. In the Dim-5/peptide structure, E227 interacts with H3R8 and D209 with H3-S10. Mutations of E227 or D209 caused predictable changes in the substrate preference, illustrating that peptide recognition of histone methyltransferases can be altered by protein design. Comparative analyses of peptide arrays with wild-type and mutant enzymes, therefore, are well suited to investigate the target specificity of protein methyltransferases and study epigenetic crosstalk

Prospective Multicenter Trial of Cervical Arthroplasty With the ROTAIO® Cervical Disc Prosthesis

Objective Anterior Cervical Discectomy and Arthroplasty (ACDA) is an established treatment for degenerative cervical disc disease and seems to be an alternative to fusion in minimizing the risk of Adjacent Segment Disease (ASD). The ROTAIO® cervical disc prosthesis is a novel unconstrained implant with a variable center of rotation aiming at physiological motion. The objective of this multicenter prospective trial was to evaluate clinical outcome and complications within 2 years. Material and Methods 120 patients (72 females and 48 males with a median age of 43.0 years; range: 23 to 60 years) underwent ACDA (ROTAIO®, SIGNUS Medical, Alzenau, Germany) and were prospectively followed for 24 months. Preoperative complaints were mainly associated with radiculopathy (n=104) or myelopathy (n=16). There were 108 monosegmental and 12 bisegmental procedures including 6 hybrid constructs. Clinical outcome was evaluated at 3, 12 and 24 months by the Visual Analogue Scale (VAS) for head, neck and arm pain, the Neck Disability Index (NDI), the Work Limitation Questionnaire (WL-26), the Patient`s Satisfaction Index (PSI) and a Quality of Life Questionnaire (SF-36). The Nurick Score, the Modified Japanese Orthopaedic Association Score (mJOA) plus a Composite Success Rate have been additionally applied. Finally, complications, the patient`s overall satisfaction and the amount of analgesics were assessed. Results Highly significant clinical improvements were observed according to NDI and VAS (p<0.0001 (arm); p<0.001 (neck); p=0.002 (head)) at all postoperative time points. Analgetic medication could be reduced after 3 months in 91.3%, after 12 months in 87.1% and after 24 months in 95.2% of patients. Doctor`s visits for cervical spine problems have been reduced in 93.8% after 24 months. Patient`s overall satisfaction was high after 3, 12 and 24 months with 83.5%, 78.4% and 79.1% of patients, while 4.1%, 6.8% and 7.0% respectively were not satisfied. The composite success rate was 77.5% after 12 months and 76.9% after 24 months. There were no major complications in this series. Slight subsidence of the prosthesis was observed in 2 patients and 3 patients demonstrated fusion after 24 months. 2 patients developed symptomatic foraminal stenosis, so that implant removal and fusion was performed. Conclusion The ROTAIO® cervical disc prosthesis is a safe and efficient treatment option for symptomatic degenerative disc disease demonstrating excellent clinical results at 2 years. Outcome proves to be stable over time with very low revision rates

Macroscopic fluorescence imaging: a novel technique to monitor retention and distribution of injected microspheres in an experimental model of ischemic heart failure.

BACKGROUND:The limited effectiveness of cardiac cell therapy has generated concern regarding its clinical relevance. Experimental studies show that cell retention and engraftment are low after injection into ischemic myocardium, which may restrict therapy effectiveness significantly. Surgical aspects and mechanical loss are suspected to be the main culprits behind this phenomenon. As current techniques of monitoring intramyocardial injections are complex and time-consuming, the aim of the study was to develop a fast and simple model to study cardiac retention and distribution following intramyocardial injections. For this purpose, our main hypothesis was that macroscopic fluorescence imaging could adequately serve as a detection method for intramyocardial injections. METHODS AND RESULTS:A total of 20 mice underwent ligation of the left anterior descending artery (LAD) for myocardial infarction. Fluorescent microspheres with cellular dimensions were used as cell surrogates. Particles (5 × 10(5)) were injected into the infarcted area of explanted resting hearts (Ex vivo myocardial injetions EVMI, n = 10) and in vivo into beating hearts (In vivo myocardial injections IVMI, n = 10). Microsphere quantification was performed by fluorescence imaging of explanted organs. Measurements were repeated after a reduction to homogenate dilutions. Cardiac microsphere retention was 2.78 × 10(5) ± 0.31 × 10(5) in the EVMI group. In the IVMI group, cardiac retention of microspheres was significantly lower (0.74 × 10(5) ± 0.18 × 10(5); p<0.05). Direct fluorescence imaging revealed venous drainage through the coronary sinus, resulting in a microsphere accumulation in the left (0.90 × 10(5) ± 0.20 × 10(5)) and the right (1.07 × 10(5) ± 0.17 × 10(5)) lung. Processing to homogenates involved further particle loss (p<0.05) in both groups. CONCLUSIONS:We developed a fast and simple direct fluorescence imaging method for biodistribution analysis which enabled the quantification of fluorescent microspheres after intramyocardial delivery using macroscopic fluorescence imaging. This new technique showed massive early particle loss and venous drainage into the right atrium leading to substantial accumulation of graft particles in both lungs

Distribution of microspheres after injection in vivo (IVMI).

<p>The IVMI-group showed distribution to both lungs (right lobe: 1 – left lobe: 3) 10 minutes after injection into the heart (2). Additionally, the homogenization (Organ – Filter – Homogenate) process involved filter retention of microspheres leading to lower microsphere counts in homogenate dilutions.</p

Overview of microsphere quantification in the IVMI group.

<p>Of half a million microspheres which were up taken by the syringe, only few (<75.000) remain in the injection site after 10 minutes of beating heart action. Additionally, further homogenization will lead to lower particle amounts. This phenomenon should be considered when quantifying microspheres in homogenate dilutions. The overall summation of fluorescence signals, retained in filters and organ homogenates respectively, resulted in comparable microsphere counts to whole organ IVIS measurements before homogenization.</p

Fluorescence analysis of standard microsphere dilutions.

<p><b>A</b> Correlation between microsphere amounts and fluorescence signals, which allows the calculation of microsphere concentrations in the function of fluorescence signals. <b>B</b> Standard dilutions between 250.000 (a) and 15.625 (e) were arranged on 96-well plates.</p