Preoperative depression, lumbar fusion, and opioid use: an assessment of postoperative prescription, quality, and economic outcomes.

OBJECTIVE Preoperative depression has been linked to a variety of adverse outcomes following lumbar fusion, including increased pain, disability, and 30-day readmission rates. The goal of the present study was to determine whether preoperative depression is associated with increased narcotic use following lumbar fusion. Moreover, the authors examined the association between preoperative depression and a variety of secondary quality indicator and economic outcomes, including complications, 30-day readmissions, revision surgeries, likelihood of discharge home, and 1- and 2-year costs. METHODS A retrospective analysis was conducted using a national longitudinal administrative database (MarketScan) containing diagnostic and reimbursement data on patients with a variety of private insurance providers and Medicare for the period from 2007 to 2014. Multivariable logistic and negative binomial regressions were performed to assess the relationship between preoperative depression and the primary postoperative opioid use outcomes while controlling for demographic, comorbidity, and preoperative prescription drug-use variables. Logistic and log-linear regressions were also used to evaluate the association between depression and the secondary outcomes of complications, 30-day readmissions, revisions, likelihood of discharge home, and 1- and 2-year costs. RESULTS The authors identified 60,597 patients who had undergone lumbar fusion and met the study inclusion criteria, 4985 of whom also had a preoperative diagnosis of depression and 21,905 of whom had a diagnosis of spondylolisthesis at the time of surgery. A preoperative depression diagnosis was associated with increased cumulative opioid use (ß = 0.25, p < 0.001), an increased risk of chronic use (OR 1.28, 95% CI 1.17-1.40), and a decreased probability of opioid cessation (OR 0.96, 95% CI 0.95-0.98) following lumbar fusion. In terms of secondary outcomes, preoperative depression was also associated with a slightly increased risk of complications (OR 1.14, 95% CI 1.03-1.25), revision fusions (OR 1.15, 95% CI 1.05-1.26), and 30-day readmissions (OR 1.19, 95% CI 1.04-1.36), although it was not significantly associated with the probability of discharge to home (OR 0.92, 95% CI 0.84-1.01). Preoperative depression also resulted in increased costs at 1 (ß = 0.06, p < 0.001) and 2 (ß = 0.09, p < 0.001) years postoperatively. CONCLUSIONS Although these findings must be interpreted in the context of the limitations inherent to retrospective studies utilizing administrative data, they provide additional evidence for the link between a preoperative diagnosis of depression and adverse outcomes, particularly increased opioid use, following lumbar fusion.

Cell-secreted matrices perpetuate the bone-forming phenotype of differentiated mesenchymal stem cells.

Prior to transplantation, mesenchymal stem/stromal cells (MSCs) can be induced toward the osteoblastic phenotype using a cocktail of soluble supplements. However, there is little evidence of differentiated MSCs directly participating in bone formation, suggesting that MSCs may either die or revert in phenotype upon transplantation. Cell-secreted decellularized extracellular matrices (DMs) are a promising platform to confer bioactivity and direct cell fate through the presentation of a complex and physiologically relevant milieu. Therefore, we examined the capacity of biomimetic DMs to preserve the mineral-producing phenotype upon withdrawal of the induction stimulus. Regardless of induction duration, ranging up to 6 weeks, MSCs exhibited up to a 5-fold reduction in osteogenic markers within 24 h following stimulus withdrawal. We show that seeding osteogenically induced MSCs on DMs yields up to 2-fold more calcium deposition than tissue culture plastic, and this improvement is at least partially mediated by increasing actin cytoskeletal tension via the ROCK II pathway. MSCs on DMs also secreted 25% more vascular endothelial growth factor (VEGF), a crucial endogenous proangiogenic factor that is abrogated during MSC osteogenic differentiation. The deployment of DMs into a subcutaneous ectopic site enhanced the persistence of MSCs 5-fold, vessel density 3-fold, and bone formation 2-fold more than MSCs delivered without DMs. These results underscore the need for deploying MSCs using biomaterial platforms such as DMs to preserve the in vitro-acquired mineral-producing phenotype and accelerate the process of bone repair.

Arthroscopically Assisted Versus Standard Open Reduction and Internal Fixation Techniques for the Acute Ankle Fracture.

BACKGROUND: Ankle fractures represent one of the most common orthopaedic injuries requiring operative treatment. Although open reduction and internal fixation (ORIF) of ankle fractures leads to good results in most patients, poor functional outcomes continue to be reported in some patients for whom anatomic reduction was achieved. It has been theorized that these lesser outcomes may in part be due to a component of missed intra-articular injury that reportedly ranges between 20% and 79%, although to date the true explanation for this subset of lower functional outcomes remains unknown. Such concerns have recently spawned novel techniques of arthroscopically assisted ankle fracture assessment in hopes of enabling better detection and treatment of concomitant intra-articular ankle injuries. The purpose of this systematic review was to summarize the literature comparing standard ORIF to arthroscopically assisted ORIF (AAORIF) for ankle fractures. METHODS: A systematic review of the English literature was performed using the PubMed database to access all studies over the last 50 years that have documented the functional outcomes of acute ankle fracture management using either a traditional ORIF or an AAORIF technique in the adult population. Relevant publications were analyzed for their respective Levels of Evidence as well as any perceived differences reported in operative time, outcomes, and complications. RESULTS: A total of only 14 ORIF and 4 AAORIF papers fit the criteria for review. There is fair quality (grade B) evidence to support good to excellent outcomes following traditional ORIF of malleolar fractures. There is fair-quality (grade B) evidence that ankle arthroscopy can be successfully employed for identification and treatment of intra-articular injuries associated with acute ankle fractures, but insufficient (grade I) evidence examining the functional outcomes and complication rates after treatment of these injuries and little documentation that this approach portends any improvement in patient outcome over historical techniques. There is also insufficient (grade I) evidence from 2 prospective randomized studies and 1 case-control study to provide any direct comparative data on functional outcomes, complication rates or total operative time between AAORIF and ORIF for the treatment of acute ankle fractures. CONCLUSIONS: Ankle arthroscopy is a valuable tool in identifying and treating intra-articular lesions associated with ankle fractures. The presence of such intra-articular pathology may lead to the unexpectedly poor outcomes seen in some patients who undergo surgical fixation of ankle fractures with otherwise anatomic reduction on postoperative radiographs; the ability to diagnose and address these lesions therefore has the potential to improve patient outcomes. To date, however, currently available literature has not shown that treatment of these intra-articular injuries provides any improvement in outcomes over standard ORIF, and few prospective randomized controlled studies have been performed comparing these 2 operative techniques-rendering any suggestion that AAORIF improves clinical outcomes over traditional ORIF difficult to justify. Further research is indicated for what may be a potentially promising surgical adjunct before we can advocate its routine use in these patients. LEVEL OF EVIDENCE: Level II, systematic review.

On-chip endothelial inflammatory phenotyping.

Atherogenesis is potentiated by metabolic abnormalities that contribute to a heightened state of systemic inflammation resulting in endothelial dysfunction. However, early functional changes in endothelium that signify an individual's level of risk are not directly assessed clinically to help guide therapeutic strategy. Moreover, the regulation of inflammation by local hemodynamics contributes to the non-random spatial distribution of atherosclerosis, but the mechanisms are difficult to delineate in vivo. We describe a lab-on-a-chip based approach to quantitatively assay metabolic perturbation of inflammatory events in human endothelial cells (EC) and monocytes under precise flow conditions. Standard methods of soft lithography are used to microfabricate vascular mimetic microfluidic chambers (VMMC), which are bound directly to cultured EC monolayers. These devices have the advantage of using small volumes of reagents while providing a platform for directly imaging the inflammatory events at the membrane of EC exposed to a well-defined shear field. We have successfully applied these devices to investigate cytokine-, lipid- and RAGE-induced inflammation in human aortic EC (HAEC). Here we document the use of the VMMC to assay monocytic cell (THP-1) rolling and arrest on HAEC monolayers that are conditioned under differential shear characteristics and activated by the inflammatory cytokine TNF-α. Studies such as these are providing mechanistic insight into atherosusceptibility under metabolic risk factors.