Hydrogel + Stem Cells Improve Disc Conditions in Goats
This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
One of the key changes leading to intervertebral disc degeneration is the loss of complex proteoglycans in the nucleus pulposus (NP), which leads to a loss of water avidity, physiologic dysfunction, NP tissue rigidity, and disruption of surrounding disc tissues. In humans, these changes can begin as early as the second decade of life. One of the difficulties in developing cellular therapies to address these changes is creating a hydrogel that can support effective delivery of mesenchymal stem cells (MSCs).
University of Pennsylvania researchers chemically induced degeneration in lumbar discs in adult male goats. After 12 weeks, some of the degenerating discs were injected with either a hydrogel alone (n=9 discs) or hydrogel with 10 million mesenchymal stem cells per ml (n=10 discs). The remaining discs received neither injection. Two weeks later, researchers analyzed disc height, hydrogel distribution, and MSC localization using green fluorescent protein (GFP) immunostaining.
After 12 weeks of disc degeneration, disc height was approximately 66% of pre-intervention levels. After 2 weeks of the treatment phase, researchers found an insignificant increase in height in the hydrogel-alone discs, and a significant 7.6% height increase in the hydrogel-with-MSCs discs. Imaging revealed that the majority of hydrogel was located in the NPs of the treated discs.
Treated discs exhibited improved overall histological grade compared to untreated discs, but the improvement was significant only in discs treated with hydrogel + MSCs. The fact that GFP-positive MSCs were identified both in the hydrogel itself and in the surrounding NP tissue suggests that MSCs migrated beyond the injection site.
The question remains whether we can similarly improve physiology in the wide spectrum of degenerative disc disease experienced by humans. Let’s hope that future investigations yield positive findings.
Teamwork Necessary When Treating Patients with Syringomyelia + Scoliosis
Most orthopaedic spine surgeons and neurosurgeons have come to understand that syringomyelia plays a role in some cases of scoliosis, and that the spinal-cord condition may increase the risk of cord injury during deformity-correction surgery. In the August 19, 2020 issue of JBJS, Tan et al. investigate whether radiographic and clinical outcomes after 1-stage posterior spinal fusion to correct scoliosis secondary to syringomyelia differ between patients with syringomyelia related to Chiairi-I malformation (CIM) and those with idiopathic syringomyelia.
The short answer is “no.” Although researchers found larger preoperative syringeal parameters in the CIM group, up through 2 years after scoliosis-correction surgery, they detected no significant between-group differences in coronal/sagittal parameters or in scores from the 5 domains of the Scoliosis Research Society-22 questionnaire. Moreover, the preoperative neurological status and intraoperative neuromonitoring signals were similar in both groups.
In commenting on these findings, Kent A. Reinker, MD, points out that patients who had received preoperative neurological treatment for the syrinx were excluded from the study, so “the results … do not necessarily apply to patients who have had neurological intervention prior to scoliosis surgery.” He strongly recommends that all patients with a syrinx be referred to a neurosurgeon for evaluation prior to any scoliosis surgery, concluding that “a working partnership between orthopaedic surgeons and their neurological colleagues is important when assessing these patients.”
Sustained Fevers After Spinal Fusion: A Sentinel for Infection?
Postoperative fevers occur frequently. During the first 2 to 3 days after surgery, these fevers are often due to atelectasis or the increased inflammatory response that arises from tissue injury during surgery. However, persistent postoperative fevers should be cause for concern. In the August 19, 2020 issue of The Journal, Hwang et al. examine the relationship between sustained fevers after spine instrumentation and postoperative surgical site infection.
The authors retrospectively reviewed 598 consecutive patients who underwent lumbar or thoracic spinal instrumentation. They excluded patients who underwent surgery to treat tumors or infections and those with other identified causes of fever, such as a urinary tract infection or pneumonia. Sustained fevers were defined as those that began on or after postoperative day (POD) 4 and those that started on POD 1 to 3 if they persisted until or beyond POD 5.
Sixty-eight patients (11.4%) met the criteria for a sustained fever after spinal instrumentation. Nine of those 68 (13.2%) were diagnosed with a surgical site infection. Of the 530 patients who did not have a sustained fever, only 5 (0.9%) developed a surgical site infection (p<0.001 for the between-group difference).
Further analysis revealed 3 diagnostic clues for surgical site infections among the patients with sustained fevers:
- Continuous fever (rather than cyclic or intermittent)
- Levels of C-reactive protein (CRP) >4 mg/dL after POD 7
- Increasing or stationary patterns of CRP level and neutrophil differential
In addition, the authors found that CRP levels >4 mg/dL between PODs 7 and 10 had much greater sensitivity for discriminating surgical site infection than gadolinium-enhanced magnetic resonance imaging data obtained within 1 month of the surgical procedure.
Although a vast majority (87%) of patients with sustained postoperative fevers in this study did not develop an infection, persistent fever after spine instrumentation surgery is something to be mindful of. The authors describe their findings as “tentative” and advise readers to interpret them with caution. Those caveats notwithstanding, I consider this information to be valuable because it might help prevent delays in the diagnosis of a potentially serious perioperative complication.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Owning the Bone in Spine Surgery
This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
Approximately 20% of patients who undergo spine surgery have osteoporosis, which has a significant impact on spine-surgery complications such as failure of fixation devices and collapse fractures following fusion procedures. In a recent critical analysis review, authors focus on improving outcomes by identifying and optimizing patients with osteoporosis prior to spine surgery. The multidisciplinary team involved in that process should include primary care providers, endocrinologists, physical therapists, and orthopaedic surgeons.
The predominant tool for assessing bone mineral density (BMD) is dual x-ray absorptiometry. The diagnosis is based on a T score, which represents the number of standard deviations between the patient’s BMD and that of a healthy 30-year-old woman. Standard deviations ≤─2.5 define osteoporosis. The Z score is similar to the T score but compares the patient to an age- and sex-matched individual.
A history of low-energy fracture, such as a wrist fracture following a fall from a standing height, is considered a sentinel event for suspicion of fragility fractures. The combination of a fragility fracture and low BMD is considered to be severe osteoporosis. The most common form of osteoporosis is associated with a postmenopausal decrease in mineralization, but there are other causes. These include advanced kidney disease, hypogonadism, Cushing disease, vitamin D deficiency, anorexia and/or bulimia, rheumatoid arthritis, hyperthyroidism, primary hyperparathyroidism, and some medications (e.g., anticonvulsants, corticosteroids, heparin, and proton pump inhibitors).
Forty-seven percent of patients undergoing spine deformity surgery and 64% of cervical spine surgery patients have low vitamin D levels. Postoperative bone health can be enhanced in women ≥51 years old with daily intake of 800 to 1,000 units of vitamin D and 1,200 mg of daily calcium. There is no solid evidence that pre- or postoperative bisphosphonates have a positive impact on bone healing. Conversely, some series have shown that teriparatide, an anabolic parathyroid hormone, may improve time-to-fusion and help reduce screw pull-out after lumbar fusion in postmenopausal women.
Calcitonin has been shown to reduce the incidence of vertebral compression fracture, but there is no concrete evidence that it supports spine-fusion healing. Similarly, there is no strong evidence for the use of estrogen or selective estrogen receptor modulators in this surgical scenario. There is evidence that when the human monoclonal antibody denosumab is combined with teriparatide, spine-fusion healing may be improved relative to the use of teriparatide alone. Finally, the review article identifies screw size, screw position, and other surgical considerations that can improve fixation strength.
Using the “Own the Bone” practices promulgated by the American Orthopaedic Association and the technical considerations described in this review, we should be able to mitigate osteoporosis-related postoperative complications in spine-surgery patients.
What’s New in Spine Surgery 2020
Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of OrthoBuzz summaries of these “What’s New” articles. This month, co-author Jacob M. Buchowski, MD, selected the 5 most clinically compelling findings from the >30 studies summarized in the June 17, 2020 “What’s New in Spine Surgery.”
Adult Spinal Deformity
—A recent randomized controlled trial compared operative vs nonoperative treatment among 63 adult patients with symptomatic lumbar scoliosis. An additional 223 patients were included in an observational arm of the study. At 2 years, 64% of the randomized patients in the nonoperative group had crossed over to the operative group. In an as-treated analysis, surgery was associated with superior improvement, but the high crossover rate precludes making firm comparative conclusions.
Spinal Cord Injuries
—A small study of 3 subjects1 who had sustained a spinal cord injury investigated the delivery of spatially selective stimulation to posterior nerve roots innervating the lumbosacral spinal cord through an implantable pulse generator with real-time triggering capability. This method reestablished adaptive control over previously paralyzed muscles, and subjects were eventually able to walk or bike during spatiotemporal stimulation.
Cervical Myelopathy
—A prospective study of >700 patients with degenerative cervical myelopathy2 examined the impact of surgical management on neck pain outcomes. Using the Neck Disability Index at baseline and at 6, 12, and 24 months postoperatively, researchers found significant improvement in functional and pain scores that met or exceeded the minimum clinically important difference at all follow-up time points.
Lumbar Stenosis
—A retrospective study of >1,800 patients with symptomatic lumbar stenosis3 investigated whether pain improvements could be obtained surgically with decompression alone without fusion. At 1 year after surgery, decompression alone was associated with significant improvement in all patient-reported outcomes, suggesting that a concomitant fusion may not be required in such cases.
Opioid Consumption
—A retrospective study of nearly 29,000 patients4 examined the effects of chronic preoperative opioid therapy on medium- and long-term outcomes after lumbar arthrodesis surgery. Postoperatively, chronic opioid use prior to surgery was associated with an increased risk of 90-day emergency department visits and prolonged 1- and 2-year narcotic use.
References
- Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Se´añez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J. Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. Epub 2018 Oct 31.
- Schneider MM, Tetreault L, Badhiwala JH, Zhu MP, Wilson J, Fehlings MG. 42. The impact of surgical decompression on neck pain outcomes in patients with degenerative cervical myelopathy: results from the multicenter prospective AOSpine studies. Spine J. 2019 Sep;19(9):S21.
- Bech-Azeddine R, Fruensgaard S, Andersen M, Carreon LY. 215. Outcomes of decompression without fusion in patients with lumbar spinal stenosis with back pain. Spine J. 2019 Sep;19(9):S106.
- Eisenberg JM, Kalakoti P, Hendrickson NR, Saifi C, Pugely AJ. 142. Impact of preoperative chronic opioid therapy on long-term outcomes, reoperations, complications and resource utilization after lumbar arthrodesis. Spine J. 2019 Sep; 19(9):S68-9.
Is the Tethering Juice Worth the Squeeze in AIS?
The tried-and-true treatment for progressive adolescent idiopathic scoliosis (AIS) is a posterior spinal fusion (PSF). However, for skeletally immature patients, there is increasing interest in motion-sparing growth modulation, specifically anterior vertebral body tethering (AVBT). Early reports on tethering looked promising, but the long-term prognosis remains fuzzy.
Newton et al. clarify this somewhat in the May 6, 2020 issue of JBJS. They retrospectively compared outcomes among a cohort of 23 AVBT patients followed for a mean of 3.4 years with those among a matched cohort of 26 PSF patients followed for a mean of 3.6 years. The groups were well-matched in terms of demographics and preoperative curve measurements, but the AVBT group was slightly less skeletally mature based on triradiate cartilage status and Sanders classification.
The authors found that both groups experienced significant postoperative curve correction, but the PSF group had significantly greater immediate correction of the main thoracic curve (78%) than the AVBT group (36%). Smaller immediate correction is to be expected in a growth-modulation procedure, which allows the spine to “grow straighter” over time with the tether. But at the final follow-up, the AVBT group had only a 43% curve correction versus 69% final follow-up correction in the PSF group. In addition, 9 revision procedures occurred in the AVBT group, versus none in the PSF group. Twelve patients (52%) in the AVBT group had evidence of broken tethers, with 3 of those patients undergoing revision surgery due to curve progression linked to tether breakage.
Overall, 12 of 23 patients in the AVBT group (52%) were deemed a “clinical success” at the end of the study (defined as a thoracic curve <35° without a need for a secondary fusion) while all 26 patients in the PSF group were deemed a clinical success. Anterior vertebral body tethering may have a role in the treatment of scoliosis in the growing spine, but the results to date, including these from Newton et al., lead me to question whether the tethering “juice” in its current form is worth the “squeeze.”
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Spine Surgery in Singapore Amid COVID-19
JBJS’s first COVID-19 article was about the experiences of orthopaedic surgeons in Singapore. The latest one also comes from authors in Singapore. Soh et al. focus on the impact the pandemic has had on spine surgery in that country. The authors emphasize the need to constantly review and adapt policies amid the moving target that the COVID-19 pandemic represents.
Here’s what the spine service at Soh et al.’s institution (a tertiary hospital and major trauma center) did during the first 6 weeks of the outbreak, which began in Singapore in January:
- Reduced elective spine surgeries by 50%, cancelling all spinal-deformity or revision cases and prioritizing minimally invasive and endoscopic cases that required a shorter length of stay
- Expedited all discharges with transfers to rehabilitation facilities to free up hospital beds
- Rescheduled all non-urgent spine appointments, such as those for acute back pain without neurologic complications
- Offered day-surgery nerve root injections to patients with intractable radicular symptoms
- Continued to receive and operate on emergency spinal trauma and tumor cases
As of April 7, 2020, Singapore instituted a series of heightened measures, collectively referred to as a “circuit breaker,” to further curb community spread of the virus. When the “circuit breaker” kicked in, the spine service again modified its practices. Regular operating and outpatient caseloads were further cut from 50% to 30%. Spine surgery was limited to instances in which a prolonged delay could lead to an irreversible deterioration of function that would negatively impact both the work status and quality of life of the patient.
Precautions during spine surgery are similar to those described by Liang et al for other orthopaedic procedures. Patients with confirmed or suspected COVID-19 and those with pneumonia and unknown COVID-19 status are operated on in a designated OR to avoid contamination of the main operating room and of other patients. In addition:
- Only selected equipment is brought into the OR to reduce the number of items that require cleaning after the procedure.
- The presence of health-care personnel is kept to a minimum to minimize exposure.
- The use of electrocautery is also minimized, with liberal use of suction to remove smoke and aerosols.
Soh et al. also address resident-training issues that were raised in an earlier JBJS fast-tracked article, urging that trainees be reassured they will not be penalized if called upon to modify or sacrifice their training for other responsibilities during this time.
The authors conclude with an acknowledgment of the emotional stress that accompanies a crisis like the COVID-19 pandemic: “During times of crisis, it is important to manage the fears and anxieties of our colleagues as early as possible,” they say. The orthopaedic community must “not forget to look out for one another and bear burdens for one another during this unprecedented time.”
Not All Modes in Multimodal Pain Management are Effective
The public health crisis attributed to opioids has placed increasing emphasis on other approaches to pain management, both pharmacologic and nonpharmacologic. Although some people find the term “multimodal pain management” to be ambiguous when used in clinical research or patient care, it emphasizes the need for a broader (and multidisciplinary) approach to pain management.
On the pharmacologic side, pregabalin has been found to be a variably effective adjunctive analgesic in research involving joint arthroplasty. However, its use in adolescents and children has not been adequately explored. In the February 5, 2020 issue of The Journal, Helenius et al. investigate the impact of pregabalin on total opioid consumption and pain scores in a randomized, placebo-controlled trial of 63 adolescents undergoing posterior instrumented spinal-fusion procedures. These operations are quite invasive and often result in ICU admission because of the amount of narcotics required. In this study, induction and maintenance of anesthesia and mobilization protocols were standardized for patients in both the pregabalin and placebo groups, and the authors precisely measured opioid consumption during the first 48 hours after surgery with data from patient-controlled anesthesia systems.
According to the findings from this adequately powered trial, adjunctive pregabalin did not have a positive impact on opioid consumption or postoperative pain scores. Despite these negative findings, it is my hope that this drug and others being investigated as adjunctive “modes” in multimodal pain management will be subjected to similarly designed trials, so we can accurately determine which agents work best in limiting opioid utilization.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Vancomycin Powder May Thwart Spinal Fusion
Prompted by relatively high infection rates associated with surgical treatment of pediatric spinal conditions such as scoliosis and spinal-deformity surgery in immunocompromised adults, spine surgeons have led “deep dive” clinical research into the possible benefits of local, intrawound antibiotic therapy. Consequently, the administration of antibiotic powder around the spine’s posterior elements and internal-fixation devices has become fairly widespread. But are there possible downsides to this approach that can impact patient outcomes?
This important question is addressed in the basic-science study by Ishida et al. in the October 2, 2019 issue of The Journal. The authors analyzed the fusion-specific impact of varying concentrations of intrawound vancomycin and tobramycin in a well-characterized rat model of posterolateral fusion performed with syngeneic iliac-crest allograft plus clinical bone-graft substitute. Ishida et al. found that a high dose of vancomycin (71.5 mg/kg, about 5 times higher than spine surgeons typically use) but not tobramycin had detrimental effects on fusion-mass formation in this model, as demonstrated by micro-computed tomography and histological analysis.
We now need further clinical research from the spine community to determine the optimal doses and types of intrawound antibiotics in this setting. Based on the currently available data, power calculations should be performed when designing future trials focused on this question. There seems to be little remaining doubt that locally delivered antibiotics help limit surgical-site and deep infections in spinal surgery. The impact of antibiotics on fusion rates must now be investigated further.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Mehta Casting for Early-Onset Scoliosis: Predictors of Success
The treatment of early-onset scoliosis with Mehta casting is a long process, but if successful, it can delay or obviate the need for surgery. In the September 4, 2019 issue of JBJS, Fedorak et al. examine outcomes among 38 patients (mean age of 24 ± 15 months at time of first casting) who were treated with Mehta casting and followed for a mean of 8 ± 2 years. The retrospective review identified differences between patients who had a Cobb angle ≤15° (improvement group) at the most recent follow-up and those who had a Cobb angle of >15° (no-improvement group).
Forty-nine percent of children had achieved and maintained scoliosis of ≤15° at the time of the most recent follow-up, and 73% were improved by at least 20°, although 3 children ended up relapsing after meeting recommended criteria for discontinuation of casting. There was no significant difference in thoracic-height gain between the groups, demonstrating that even when scoliosis was not corrected, growth was maintained during cast treatment.
Patients in the improvement group had a mean age of 18.9 ± 12 months and scoliosis of 48.2° ± 14° at the initiation of treatment. Here are 3 additional factors that were associated with a greater likelihood of scoliosis of ≤15°:
- A lower pre-treatment Cobb angle and traction Cobb angle
- A smaller rib-vertebral angle difference on first-in-cast radiograph
- A lower Cobb angle on first-in-cast radiograph
The authors note that although this study analyzed longer-term follow-up data than most other similar investigations, “treatment of early-onset scoliosis is not truly finished until skeletal maturity has been reached.”
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