Comparison of standard fusion with a "topping off" system in lumbar spine surgery: a protocol for a randomized controlled trial.

BACKGROUND: Fusion of lumbar spine segments is a well-established therapy for many pathologies. The procedure changes the biomechanics of the spine. Initial clinical benefits may be outweighed by ensuing damage to the adjacent segments. Various surgical devices and techniques have been developed to prevent this deterioration. "Topping off" systems combine rigid fusion with a flexible pedicle screw system to prevent adjacent segment disease (ASD). To date, there is no convincing evidence that these devices provide any patient benefits. METHODS/DESIGN: The study is designed as a randomized, therapy-controlled trial in a clinical care setting at a university hospital. Patients presenting to the outpatient clinic with degenerative disc disease or spondylolisthesis will be assessed against study inclusion and exclusion criteria. After randomization, the control group will undergo conventional fusion. The intervention group will undergo fusion with a supplemental flexible pedicle screw system to protect the adjacent segment ("topping off").Follow-up examination will take place immediately after treatment during hospital stay, after 6 weeks, and then after 6, 12, 24 and 36 months. Subsequently, ongoing assessments will be performed annually.Outcome measurements will include quality of life and pain assessments using questionnaires (SF-36™, ODI, COMI). In addition, clinical and radiologic ASD, work-related disability, and duration of work disability will be assessed. Inpatient and 6-month mortality, surgery-related data (e.g., intraoperative complications, blood loss, length of incision, surgical duration), postoperative complications, adverse events, and serious adverse events will be documented and monitored throughout the study. Cost-effectiveness analysis will also be provided. DISCUSSION: New hybrid systems might improve the outcome of lumbar spine fusion. To date, there is no convincing published data on effectiveness or safety of these topping off systems. High quality data is required to evaluate the benefits and drawbacks of topping off devices. If only because these devices are quite expensive compared to conventional fusion implants, nonessential use should be avoided. In fact, these high costs necessitate efforts by health care providers to evaluate the effects of these implants. Randomized clinical trials are highly recommended to evaluate the benefits or harm to the patient. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01224379.

In vitro study of biomechanical behavior of anterior and transforaminal lumbar interbody instrumentation techniques.

OBJECTIVE: To study the biomechanical behavior of lumbar interbody instrumentation techniques using titanium cages as either transforaminal lumbar interbody fusion (TLIF) or anterior lumbar interbody fusion (ALIF), with and without posterior pedicle fixation. METHODS: Six fresh-frozen lumbar spines (L1-L5) were loaded with pure moments of +/-7.5 Nm in unconstrained flexion-extension, lateral bending, and axial rotation. Specimen were tested intact, after implantation of an ALIF or TLIF cage "stand-alone" in L2-L3 or L3-L4, and after additional posterior pedicle screw fixation. RESULTS: In all loading directions, the range of motion (ROM) of the segments instrumented with cage and pedicle screw fixation was below the ROM of the intact lumbar specimen for both instrumentation techniques. A significant difference was found between the TLIF cage and the ALIF cage with posterior pedicle screw fixation for the ROM in flexion-extension and axial rotation (P < 0.05). Without pedicle screw fixation, the TLIF cage showed a significantly increased ROM and neutral zone compared with an ALIF cage "stand-alone" in two of the three loading directions (P < 0.05). CONCLUSION: With pedicle screw fixation, the ALIF cage provides a higher segmental stability than the TLIF cage in flexion-extension and axial rotation, but the absolute biomechanical differences are minor. The different cage design and approach show only minor differences of segmental stability when combined with posterior pedicle screw fixation.

Mechanisms of beta 3-adrenoceptor-induced eNOS activation in right atrial and left ventricular human myocardium.

beta-Adrenoceptors are important modulators of cardiac function. The present study investigated beta(3)-adrenergic eNOS activation in human myocardium. We measured nitric oxide (NO) liberation (diaminofluorescence) and signal transduction (immunohistochemistry, phosphorylation of eNOS(Ser1177), eNOS(Thr495), eNOS(Ser114), Akt/protein kinase B (Akt/PKB), and eNOS translocation) in human right atrial (RA, aortocoronary-bypass OP) and left ventricular nonfailing (LV, rejected donor hearts) myocardium after application of BRL 37344 (BRL), a preferential beta(3)-adrenoceptor agonist. In both RA and LV, BRL (10 microl) induced a liberation of NO. An eNOS activation via translocation was only observed in RA after application of BRL (10 microM). Yet, the NO liberation in both LV and RA was accompanied by phosphorylation of eNOS(Ser1177) and Akt/PKB. BRL-induced eNOS phosphorylation was abolished by LY292004, a blocker of PI-3 kinase. eNOS-Ser(114) phosphorylation was unchanged in RA, but decreased in LV after beta(3)-adrenergic stimulation. BRL did not alter phosphorylation of eNOS(Thr495). In conclusion, receptor-dependent eNOS activation is differentially regulated in the human heart. In the left ventricle, eNOS activation via phosphorylation seems to be of major importance, whereas in human atrial myocardium eNOS translocation is the predominant mechanism induced by beta(3)-adrenergic activation.