Value of single-level circumferential fusion: a 10-year prospective outcomes and cost-effectiveness analysis comparing posterior facet versus pedicle screw fixation.

PURPOSE: To compare the clinical and economic outcomes of facet versus pedicle screw instrumentation for single-level circumferential lumbar spinal fusion. METHODS: Outcomes included self-assessment of back and leg pain, pain drawing, ODI, pain medication usage, and procedure success. The CEA was based on the 10-year data collected, and the base-case was from a US payer perspective. Costs included the index surgery, additional surgeries, outpatient/ED visits, and medications. To determine quality-adjusted life years (QALYs), ODI scores were used to predict SF-6D utilities. Sensitivity analyses were performed from a modified payer perspective including device costs and from a societal perspective including productivity loss. Discounted and undiscounted incremental costs and QALYs were calculated. Bootstrapping was performed to estimate the distribution of incremental costs and effects. RESULTS: Clinical improvement was significant from pre-op to 10-year follow-up for both groups (p < 0.01 for all outcomes scales). Outcomes were significantly better for back pain and ODI for the facet versus pedicle group at all follow-up periods > 1 year (p < 0.05). In the CEA base-case, facets had more QALYs (0.68) and lower costs (- $8650) per person compared with pedicle screws. Therefore, facets were dominant (i.e., provided cost savings and greater QALYs) compared with pedicle screws. Facets had a 97% probability of being below a willingness-to-pay threshold of $20,000 per QALY gained and were estimated to be dominant over pedicle screws in 84% of the simulations. CONCLUSION: One-level circumferential spinal fusion using facet screws was clinically superior and provided cost savings compared with pedicle screw instrumentation in the USA.

Cardiac-Referenced Leukocyte Telomere Length and Outcomes After Cardiovascular Surgery.

Leukocyte telomere shortening reflects stress burdens and has been associated with cardiac events. However, the patient-specific clinical value of telomere assessment remains unknown. Moreover, telomere shortening cannot be inferred from a single telomere length assessment. The authors investigated and developed a novel strategy for gauging leukocyte telomere shortening using autologous cardiac atrial referencing. Using multitissue assessments from 163 patients who underwent cardiovascular surgery, we determined that the cardiac atrium-leukocyte telomere length difference predicted post-operative complexity. This constituted the first evidence that a single-time assessment of telomere dynamics might be salient to acute cardiac care.

Fibroblast Growth Factor 9 Imparts Hierarchy and Vasoreactivity to the Microcirculation of Renal Tumors and Suppresses Metastases.

Tumor vessel normalization has been proposed as a therapeutic paradigm. However, normal microvessels are hierarchical and vasoreactive with single file transit of red blood cells through capillaries. Such a network has not been identified in malignant tumors. We tested whether the chaotic tumor microcirculation could be reconfigured by the mesenchyme-selective growth factor, FGF9. Delivery of FGF9 to renal tumors in mice yielded microvessels that were covered by pericytes, smooth muscle cells, and a collagen-fortified basement membrane. This was associated with reduced pulmonary metastases. Intravital microvascular imaging revealed a haphazard web of channels in control tumors but a network of arterioles, bona fide capillaries, and venules in FGF9-expressing tumors. Moreover, whereas vasoreactivity was absent in control tumors, arterioles in FGF9-expressing tumors could constrict and dilate in response to adrenergic and nitric oxide releasing agents, respectively. These changes were accompanied by reduced hypoxia in the tumor core and reduced expression of the angiogenic factor VEGF-A. FGF9 was found to selectively amplify a population of PDGFRß-positive stromal cells in the tumor and blocking PDGFRß prevented microvascular differentiation by FGF9 and also worsened metastases. We conclude that harnessing local mesenchymal stromal cells with FGF9 can differentiate the tumor microvasculature to an extent not observed previously.

Collagenase-resistant collagen promotes mouse aging and vascular cell senescence.

Collagen fibrils become resistant to cleavage over time. We hypothesized that resistance to type I collagen proteolysis not only marks biological aging but also drives it. To test this, we followed mice with a targeted mutation (Col1a1(r/r) ) that yields collagenase-resistant type I collagen. Compared with wild-type littermates, Col1a1(r/r) mice had a shortened lifespan and developed features of premature aging including kyphosis, weight loss, decreased bone mineral density, and hypertension. We also found that vascular smooth muscle cells (SMCs) in the aortic wall of Col1a1(r/r) mice were susceptible to stress-induced senescence, displaying senescence-associated ß-galactosidase (SA-ßGal) activity and upregulated p16(INK4A) in response to angiotensin II infusion. To elucidate the basis of this pro-aging effect, vascular SMCs from twelve patients undergoing coronary artery bypass surgery were cultured on collagen derived from Col1a1(r/r) or wild-type mice. This revealed that mutant collagen directly reduced replicative lifespan and increased stress-induced SA-ßGal activity, p16(INK4A) expression, and p21(CIP1) expression. The pro-senescence effect of mutant collagen was blocked by vitronectin, a ligand for αvß3 integrin that is presented by denatured but not native collagen. Moreover, inhibition of αvß3 with echistatin or with αvß3-blocking antibody increased senescence of SMCs on wild-type collagen. These findings reveal a novel aging cascade whereby resistance to collagen cleavage accelerates cellular aging. This interplay between extracellular and cellular compartments could hasten mammalian aging and the progression of aging-related diseases.