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The Spine Blog

Friday, August 23, 2019

Adult deformity surgery can markedly improve patient quality of life. However, these complex procedures are associated with high complication and re-operation rates. Prior literature has been mixed on whether experiencing a significant complication following adult deformity surgery leads to worse medium-term patient-reported outcomes (PROs). The Adult Symptomatic Lumbar Scoliosis study was a multicenter investigation in which 286 patients enrolled in either a randomized or observational arm comparing surgery to non-operative treatment for adult lumbar scoliosis. The primary paper was published earlier this year and demonstrated significantly better outcomes for patients treated surgically.1 In order to answer the question about the association between complications and PROs, Dr. Smith and the other study investigators stratified surgical outcomes based on the presence of experiencing a serious adverse event (SAE). These generally included reoperation for any cause, new neurological deficit, or significant medical complication. Of a total 173 surgical patients, they reported 97 SAEs in 67 patients (39% of patients). The most common SAEs were implant failure or pseudarthrosis resulting in reoperation (n=29), proximal junctional kyphosis leading to reoperation (n=10), or new neurological deficit (n=17). The SAE patients were significantly more likely to have an autoimmune disorder (18% vs. 5%) and diabetes (11% vs. 3%) compared to the no-SAE patients, though both groups had similar deformity and underwent similar operations. The SAE group did have 800 cc more blood loss at surgery. At both 2 and 4 years, they found that the patients with an SAE had less improvement on the SRS-22 (about 0.3 points less improvement) and ODI (about 6 points less improvement). Surgical patients with an SAE still improved markedly more than the non-operative patients (about 8 points more on the ODI at both 2 and 4 years).

This secondary analysis of a very well done study suggests that experiencing a SAE associated with adult deformity surgery does lead to worse PROs at both 2 and 4 years. While this is not surprising, it is in contrast to some prior studies that suggested no difference in PROs between patients with and without complications. The current study was also strengthened by having a non-operative group, which really did not improve at all over 2-4 years. A significant question raised by this study is the magnitude of the negative effect of an SAE. The study did not have sufficient numbers to be able to look at the effect of specific complications on outcomes (such a study would likely require thousands of patients), though it is safe to assume that different complications have different effects in terms of the duration and magnitude of worsened outcomes. A patient with a major new neurological deficit that does not improve would have a lifetime of worse outcomes compared to a patient who experiences proximal junctional kyphosis, a reoperation, and then a return to good outcomes. The authors also did not appear to control for baseline differences in medical comorbidities, smoking, or worker's compensation status, which are known to affect PROs. The SAE group did tend to have worse medical comorbidities, and it is difficult to know how much the SAE vs. the medical comorbidity contributed to the worse outcome. The authors could have theoretically controlled for this statistically, though the study may have not included enough patients to do this effectively. This study does add some realism to the discussion about SAEs in adult deformity surgery, namely that SAEs do have a detrimental effect on PROs. Patients should be advised that these complex procedures will likely result in improvement in their outcomes but come at the cost of a 40% SAE rate, a 26% 4 year reoperation rate, and a significant recovery time. These statistics also reflect the outcomes of the world's experts at deformity surgery, and complication rates are likely higher at less experienced institutions.

Please read Dr. Kelly's article in the September 1 issue. Does this change how you view the effect of complications in adult deformity surgery? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS
Associate Web Editor

 

REFERENCE

1.            Kelly MP, Lurie JD, Yanik EL, et al. Operative Versus Nonoperative Treatment for Adult Symptomatic Lumbar Scoliosis. J Bone Joint Surg Am 2019;101:338-52.

 


Friday, August 16, 2019

Since Modic changes (MC) were first described over 30 years ago, spine care practitioners have struggled with how to interpret the imaging finding. Their etiology remains obscure, with hypotheses ranging from inflammation to microinjury to infection. The literature on the association between MCs and low back pain (LBP) is mixed, and there is scant data on the role of MCs as long-term prognostic indicators. In order to better assess the association between MCs and long-term back pain outcomes, Dr. Udby and colleagues from Denmark studied 170 chronic LBP patients enrolled in an RCT comparing cognitive training and PT who had a baseline lumbar MRI and follow-up 13 years after the original MRI. The original study included 204 patients and found no difference in outcomes with the cognitive training and PT. At baseline, 40% of patients had MCs (the majority of which were MC Type I), the average age was 41, and just over 50% were female. There were no significant baseline differences between the MC+ and MC- groups in terms of demographic characteristics, pain, or function. At 13 year follow-up, the MC+ group had significantly better Roland-Morris Disability Questionnaire scores (7.4 vs. 9.6) and significantly fewer sick leave days related to LBP over the past year (9 vs.23). Other outcome scores were similar between the two groups, with some trends towards slightly better long-term outcomes in the MC+ group.

This is an interesting study that suggests that MCs are not a negative prognostic indicator in the long-term. A key aspect of the study to understand is that all patients had chronic LBP at baseline (reporting LBP in at least 4/12 months prior to enrollment). Most population-based studies have found at least some association between MCs and LBP, though this association seems much weaker or non-existent in the chronic LBP population. This study also did not include follow-up MRI, which the authors explained was due to changes in MRI technology, namely the use of much higher Tesla magnets over time. They felt that comparing the findings of a modern high Tesla MRI to the low Tesla magnet used in 2004-2005 would have biased the results. There is fairly good data in the literature documenting the changes in MCs over time, though how this relates to clinical outcomes is less clear. The authors hypothesized that the MC+ patients may have had somewhat better long-term outcomes as compared to the MC- patients as the inflammation associated with MCs tends to subside over time, which could result in less LBP. The MC- patients may have had a different underlying pathology which was less likely to improve spontaneously. The magnitude of the outcome differences between the two groups was relatively small, so concluding that MC+ patients have meaningfully better long-term outcomes is a bit of a stretch. However, the data strongly suggest that MCs are not a negative prognostic factor in the chronic LBP population and should probably not be used to predict outcomes or guide treatment. Thirty years after their description, the spine community still does not know what to make of MCs.

Please read Dr. Udby's paper in the September 1 issue. Does this change your view of how you consider MCs in your practice? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS

Associate Web Editor


Saturday, August 10, 2019

There has long been concern that industry funded studies, especially those in which authors have a direct financial relationship with the device manufacturer, are prone to bias in study design, performance, interpretation, and publication. The main efforts to mitigate this effect have been around author conflict of interest (COI) disclosure—both voluntary and through the Open Payments website-- and listing of all studies prior to commencement on clincaltrials.gov. While this has led to an increase in transparency, it is not clear if these programs have had any effect on the level of bias in industry-funded studies. In order to assess the relationship between author conflict of interest and outcomes in the lumbar disk arthroplasty (LDA) literature, Jordan Guntin and colleagues from Rush University Medical Center performed a systematic review of the LDA literature from 2011-2018. They identified 57 eligible studies, about half of which were level 4 studies and one third of which were level 1 studies. Fifty-three percent of studies had at least one author with a COI, and the vast majority of these involved a direct financial relationship with the device manufacturer. Studies from the United States were significantly more likely to have an author with a COI (77% vs. 43%). Ninety percent of the studies listed the COI, while the authors identified the COI through other sources (i.e. Open Payments) in the remaining 10%. Studies including an author with a COI were 60% more likely to report a favorable outcome (83% vs. 52%, p=0.02).

The results of this study come as no surprise, and the authors have done a good job in quantifying the effect of author COI on the LDA literature. The main question left unanswered, and which may be unanswerable, is the mechanism through which author COI affects the outcomes of published studies. One would hope that it is not through direct fraud by the device manufacturer and authors, and this seems unlikely in an era of increasing transparency. More likely is some type or types of bias, which can involve study design, patient selection, defining "success", statistical analysis, data interpretation, and the decision to publish equivocal or unfavorable results. Given that these biases are seemingly not eliminated through COI disclosure, other mechanisms may need to be considered in the future. In an ideal world, spine investigators could receive non-industry funds that would allow them to perform high quality, unbiased research. However, government and foundation funding for studies of this kind is exceedingly hard to obtain. Another possibility would be to require industry to provide the funding to a neutral organization that then selects the investigators so that the device manufacturer is held at arm's length from the study. This would prevent any bias in the study design, performance, interpretation, or publication. This study and others like it have created an appropriately high level of skepticism among investigators, spine surgeons, and patients. While this skepticism helps to limit overly enthusiastic adoption of new technology that has not been vetted in studies without COI (LDA is a great case in point), it may also inappropriately slow adoption of effective new technology. While it may be non-intuitive, industry and patients may both be best served through the creation of neutral organizations tasked to perform studies evaluating new devices and technology.

Please read Mr. Guntin's article in the August 15 issue. Does this change how you view the association between author COI and published outcomes? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS
Associate Web Editor

 

Friday, August 2, 2019

Lumbar and cervical degeneration frequently coexist as the pathophysiology and predisposing factors leading to degenerative changes in the different regions of the spine are likely similar. Patients undergoing major thoracolumbar deformity surgery are theoretically at increased risk of cervical spinal cord injury if they have cervical stenosis due to the long duration of these cases in which the neck may be positioned in extension and during which hypotension is common. Dr. Shimizu and the spine surgeons at Columbia were aware of the common concurrence of thoracolumbar deformity and cervical degeneration and began ordering pre-operative cervical MRIs on all adult patients undergoing major thoracolumbar deformity surgery (> 5 levels). They rated each level in the cervical spine using the Cord Compression index, which provides a 0-3 grading system. They classified patients with Grade 2 (loss of CSF around cord) and Grade 3 (clear cord compression) compression as having significant cord compression. Their cohort include 121 patients (82% female, average age 55, range 23-82), the majority (56%) of whom were diagnosed with adult idiopathic scoliosis. The group had relatively severe coronal deformity (average main thoracic curve 40 degrees, thoracolumbar or lumbar curve 45 degrees) with more mild sagittal imbalance (PI-LL mismatch 8.5 degrees, SVA 46 mm). They found that 41 (34%) patients had significant cervical cord compression. Of these 41 patients, 35 were asymptomatic with no or subtle exam findings, and 6 were clearly myelopathic. As a result of the surveillance for cervical pathology, four patients underwent cervical surgery prior to their thoracolumbar deformity procedure. Multivariate regression demonstrated that age, BMI, and increasing PI-LL mismatch were risk factors for cervical cord compression. In fact, 8/14 of patients in their 70s and 2/2 patients in their 80s had significant cervical cord compression.

This is a well-designed study that documents the relatively high prevalence of cervical cord compression in patients undergoing adult deformity surgery. Given the common pathophysiology leading to both cervical and thoracolumbar disease, the results are not surprising. The authors' definition of significant cord compression likely included many patients with effacement of the CSF without actual cord compression, and 32/41 had the more mild, Grade 2 findings. This does beg the question of what to do with a non-myelopathic patient planning to undergo major deformity surgery who is found to have significant cervical cord compression. Given that cervical surgery is generally not indicated for this patient if they were to present without thoracolumbar deformity, it seems most appropriate to proceed with the deformity operation using appropriate neuromonitoring techniques to ensure that positioning does not cause a problem with the cervical spinal cord. While the authors state that they obtain cervical MRIs on all of their thoracolumbar deformity patients undergoing surgery, this likely changes management rarely. The 4 patients who underwent cervical surgery prior to thoracolumbar deformity surgery were all myelopathic on clinical exam, suggesting that a thorough cervical history and physical in all thoracolumbar deformity patients might be a better, more cost-effective screening tool than an MRI on all deformity patients. This paper is a good reminder to evaluate the cervical spine in all patients with significant thoracolumbar disease.

Please read Dr. Shimizu's article in the August 1 issue. Does this motivate you to obtain cervical MRIs in your adult deformity patients? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS

Associate Web Editor


Friday, July 26, 2019

The spine surgery community has a large variety of fusion adjuncts and bone graft options available, including iliac crest bone graft, local bone graft, allograft, demineralized bone matrix, mesenchymal stem cells, calcium phosphate ceramics, and BMP-2. They all have risks and benefits, with the most effective options (i.e. iliac crest bone graft and BMP-2) also having the highest risk of complications. BMP-2 is also extremely expensive. The other lower cost, lower risk options are also less effective. As such, investigators have been in search of an effective, low complication, low cost fusion adjunct. One option that has been evaluated in the fracture healing literature is the cholesterol lowering agent simvastatin. This medication has been shown to stimulate bone formation through similar pathways as BMP-2 and also prevent osteoblast apoptosis. In order to assess simvastatin as a spinal fusion adjunct, Dr. Iyer and colleagues from the Hospital for Special Surgery developed simvastatin eluting nanoparticles (SimNP) and evaluated their effectiveness in both cell culture and a rat fusion model. In cell culture, SimNP treated osteoblasts had greater alkaline phosphatase activity and generated more mRNA for multiple markers of bone formation compared to controls. They also performed uninstrumented, intertransverse fusions at L4-L5 using iliac crest bone graft in 40 rats. The rats were treated with SimNP, blank nanoparticles (BlankNP), or simvastatin alone (Sim). The SimNP rats had higher x-ray fusion scores at 4 weeks and 9 weeks and at 9 weeks had a significantly higher fusion rate compared to the BlankNP rates based on manual inspection of the fusion (43% vs. 0%). The Sim rats had an intermediate fusion rate (22%). Based on these findings, the authors concluded that simvastatin was an effective adjunct to lumbar fusion in a rat model.

Rarely do basic science articles generate much attention, so the authors should be congratulated for performing such a promising rat study. While there is a long way to go from the basic science lab and small animal operating room to use in humans, the data are promising. It seems clear from this and other papers that simvastatin is an osteoinductive agent. Additionally it is low cost, and it seems to have a good safety profile. Whether it turns out to be effective in humans remains to be seen, and much work needs to be done on dosing and delivery methods. However, there is a major unmet need in the bone graft substitute/fusion adjunct market, despite the plethora of products currently available. Other than BMP-2, no other synthetic agent or allograft product has been shown to be effective. Unfortunately, BMP-2 is bordering on prohibitively expensive and has an undesirable side-effect profile. The only studies currently listed on ClinicalTrials.gov evaluating locally applied simvastatin as an osteoinductive agent are looking at dentistry applications. Hopefully orthopaedic and spine investigators will continue to work on simvastatin and evaluate it in human studies looking at fracture healing and spinal fusion in the future. Maybe in ten years we will all be adding simvastatin to our bone graft.

Please read Dr. Iyer's article on this topic in the August 1 issue. What do you think of simvastatin as a fusion adjunct? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS

Associate Web Editor