Preoperative medical assessment for adult spinal deformity surgery: a state-of-the-art review.

INTRODUCTION: The purpose of this study is to provide a state-of-the-art review regarding risk factors for perioperative complications in adult spinal deformity (ASD) surgery. The review includes levels of evidence for risk factors associated with complications in ASD surgery. METHODS: Using the PubMed database, we searched for complications, risk factors, and adult spinal deformity. The included publications were assessed for level of evidence as described in clinical practice guidelines published by the North American Spine Society, with summary statements generated for each risk factor (Bono et al. in Spine J 9:1046-1051, 2009). RESULTS: Frailty had good evidence (Grade A) as a risk for complications in ASD patients. Fair evidence (Grade B) was assigned for bone quality, smoking, hyperglycemia and diabetes, nutritional status, immunosuppression/steroid use, cardiovascular disease, pulmonary disease, and renal disease. Indeterminate evidence (Grade I) was assigned for pre-operative cognitive function, mental health, social support, and opioid utilization. CONCLUSIONS: Identification of risk factors for perioperative complications in ASD surgery is a priority for empowering informed choices for patients and surgeons and managing patient expectations. Risk factors with grade A and B evidence should be identified prior to elective surgery and modified to reduce the risk of perioperative complications.

Proximal Junctional Spondylodiscitis Following Adult Spinal Deformity Surgery: Case Series and Review of the Literature.

BACKGROUND: Proximal junctional failure (PJF) following multilevel thoracolumbar instrumented to the pelvis for adult spinal deformity (ASD) is relatively uncommon but considerably disabling. While the leading etiology is mechanical, other rarer etiologies can play a role in its development. The purpose of this study was to present a case series of ASD patients who experienced PJF secondary to proximal junctional spondylodiscitis (PJS) after long-segment thoracolumbar posterior instrumented fusions. METHODS: Adult patients who underwent posterior instrumented fusions at a single academic center between 2017 and 2020 and subsequently developed PJS were retrospectively reviewed. Patient demographics, operative details, clinical presentation, culture data, and management approach were evaluated. RESULTS: Three patients developed PJS and were included for analysis (mean age 67 years [range, 58-76]; women: 2). Indication for all index operations was symptomatic ASD after failed conservative management. Clinical presentation ranged from mild back pain to severe neurological compromise. Average time to infection and PJF after the index procedure was 11 months (range, 3 months-2 years). All 3 patients were successfully managed with urgent revision surgery including surgical debridement and postoperative antibiotics. CONCLUSION: PJS is a rare yet potentially devastating complication following long-segment posterior thoracolumbar instrumented fusions for ASD. It is critical that surgeons maintain a high index of suspicion of infection when managing PJF given the potential neurological morbidity of PJS. CLINICAL RELEVANCE: This report highlights a rare but important cause of PJF following ASD surgery. It is critical that one maintains a high index of suspicion of infection when managing PJF.

Early Medical Complications and Delayed Discharge after Spinopelvic Fusion: A Comparative Analysis of 887 NSQIP Cases from 2006 to 2016.

INTRODUCTION: The effect of pelvic fixation on postoperative medical complications, blood transfusion, length of hospital stay, and discharge disposition is poorly understood. Determining factors that predispose patients to increased complications after spinopelvic fusion will help surgeons to plan these complex procedures and optimize patients preoperatively. METHODS: We conducted a retrospective cohort study using data from the ACS-NSQIP database between 2006 and 2016 of patients who underwent lumbar fusion with and without spinopelvic fixation. Data regarding demographics, complications, hospital stay, and discharge disposition were collected. RESULTS: A total of 57,417 (98.5%) cases of lumbar fusion without spinopelvic fixation (LF) and 887 (1.5%) cases of lumbar fusion with spinopelvic fixation (SPF) were analyzed. The transfusion rate in the SPF group was 59.3% vs 13% in the LF group (p < 0.001). The mean length of stay (LOS) and discharge to skilled nursing facility (SNF) were significantly different (LOS: SPF 6.5 days vs LF 3.5 days p < 0.001; SNF: SPF 21.3% vs LF 10.4% p < 0.001). After controlling for demographic differences, the overall complication rates were not significantly different between the groups (p = 0.531). The odds ratio for transfusion in the SPF group was 2.9 (p < 0.001). The odds ratio for increased LOS and increased care discharge disposition were elevated in the SPF group (LOS OR: 1.3, p < 0.012, Discharge disposition OR: 1.8, p < 0.001). CONCLUSIONS: Patients who underwent SPF had increased complications, transfusion rate, LOS, and discharge to SNF or subacute rehab facilities as compared with patients who underwent LF. SPF remains an effective technique for achieving lumbosacral arthrodesis. Surgeons should consider the implications of the associated complication profile for SPF and the value of preoperative optimization in a select cohort of patients.

Spinal Epidural Abscess: A Review of Presentation, Management, and Medicolegal Implications.

Spinal epidural abscess (SEA) is a rare condition associated with significant morbidity and mortality. Despite advances in diagnostic medicine, early recognition of SEAs remains elusive. The vague presentation of the disease, coupled with its numerous risk factors, the diagnostic requirement for obtaining advanced imaging, and the necessity of specialized care constitute extraordinary challenges to both diagnosis and treatment of SEA. Once diagnosed, SEAs require urgent or emergent medical and/or surgical management. As SEAs are a relatively rare pathology, high-quality data are limited and there is no consensus on their optimal management. This paper focuses on presenting the treatment modalities that have been successful in the management of SEAs and providing a critical assessment of how specific SEA characteristics may render one infection more amenable to primary surgical or medical interventions. This paper reviews the relevant history, epidemiology, clinical presentation, radiology, microbiology, and treatment of SEAs and concludes by addressing the medicolegal implications of delayed treatment of the disease.

Correlation of Early Outcomes and Intradiscal Interleukin-6 Expression in Lumbar Fusion Patients.

OBJECTIVE: To determine if there is correlation between intradiscal levels of interleukin-6 (IL-6) and early outcome measures in patients undergoing lumbar fusion for painful disc degeneration. METHODS: Intervertebral disc tissue was separated into annulus fibrosus/nucleus pulposus and cultured separately in vitro in serum-free medium (Opti-MEM). Conditioned media was collected after 48 hours. The concentration of IL-6 was quantified using enzyme-linked immunosorbent assay. Pearson correlation coefficients quantified relationships between IL-6 levels and pre- and postoperative visual analogue scale (VAS) back pain and Oswestry Disability Index (ODI), as well as change in VAS/ODI. RESULTS: Sixteen discs were harvested from 9 patients undergoing anterior lumbar interbody fusion (mean age, 47.4 years; range, 21-70 years). Mean preoperative and 6-month postoperative VAS were 8.1 and 3.7, respectively. Mean preoperative and postoperative ODI were 56.2 and 25.6, respectively. There were significant positive correlations between IL-6 expression and postoperative VAS (ρ = 0.38, p = 0.048) and ODI (ρ = 0.44, p = 0.02). No significant correlations were found between intradiscal IL-6 expression and preoperative VAS (ρ = -0.12, p = 0.54). Trends were seen associating IL-6 expression and change in VAS/ODI (ρ = -0.35 p = 0.067; ρ = -0.34, p = 0.08, respectively). A trend associated IL-6 and preoperative ODI (ρ = 0.36, p = 0.063). CONCLUSION: The direct association between IL-6 expression and VAS/ODI suggests patients with elevated intradiscal cytokine expression may have worse early outcomes than those with lower expression of IL-6 after surgery for symptomatic disc degeneration.

Validity of a Novel Free-Hand Pedicle Screw Placement Training Tool.

INTRODUCTION: This study establishes the construct validity of a low-cost training platform designed for high-repetition training of the skills required for fluent use of the five specific tools described for free-hand pedicle screw placement and breach avoidance. METHODS: A total of 19 participants were included and divided into three groups based on spine surgery experience. Participants were asked to place five pedicle screws into the model. The performance was assessed by recording breaches, technical criteria (0 to 44 points), time to completion, and angulation of the screws. Success (no breaches, no protrusions) frequency (success/time) was calculated and analyzed. RESULTS: Participants included three spine surgeons, seven advanced trainees (who had placed >10 pedicle screws), and nine inexperienced trainees. None of the screws placed by the spine surgeons breached the pedicle wall. Eight of 35 screws placed by advanced trainees (22.9%) and 31 of 45 screws placed by inexperienced trainees (68.9%) had a pedicle breach. Spine surgeons had a higher median success frequency compared with inexperienced trainees and advanced trainees (P = 0.015). The time needed to place a screw decreased over time (P < 0.0001). There was a trend toward an association between increased training level and decreased time to place five screws (P = 0.076). Increased training level was associated with greater total points scored (P < 0.0001). More screws placed by inexperienced trainees were further away from the ideal pedicle axis compared with those placed by advanced trainees or spine surgeons. CONCLUSION: An association exists between training level and performance on the pedicle screw model, which suggests construct validity when evaluating our model's use for teaching surgeon learners. The model is easily assembled and is an alternative spine surgery training tool that overcomes limited availability and considerable costs of other training platforms. It can be used in high repetition to establish tool-skill fluency. LEVEL OF EVIDENCE: Level I.

Spinal Epidural Lipomatosis: A Review of Pathogenesis, Characteristics, Clinical Presentation, and Management.

STUDY DESIGN: Narrative review of available literature. OBJECTIVE: To summarize current trends in pathogenesis and management of spinal epidural lipomatosis (SEL) and suggest areas where more research would be of benefit. METHODS: The available literature relevant to SEL was reviewed. PubMed, Medline, OVID, EMBASE, Cochrane, and Google Scholar were used to review the literature. Institutional review board approval is not applicable for this study. RESULTS: This article clearly summarizes current trends in the pathogenesis and management of SEL. CONCLUSIONS: Possible etiologies of SEL include exogenous steroid use, endogenous steroid hormonal disease, obesity, surgery induced, and idiopathic disease. Comorbidities such as acquired immunodeficiency syndrome and Scheuermann's disease have also been implicated in the pathogenesis of SEL. Steroid-induced SEL seems to have a proclivity for the thoracic region of the spine and has a higher incidence of paraplegia when compared with other forms. Several treatment modalities exist for SEL and are dictated by the underlying cause of the disorder. These include weight reduction, cessation of steroid medications, treatment of underlying endocrine abnormalities, and surgical decompression. Conservative treatments generally aim to decrease the thickness of adipose tissue in the epidural space, but the majority of patients tend to undergo surgical decompression to relieve neurologic symptoms. Surgical decompression provides a statistically significant reduction in symptoms, but postoperative mortality is high, influenced primarily by the patient's preoperative comorbidities. Physicians should consider the underlying cause of SEL in a given patient before pursuing specific treatment modalities, but alarm symptoms, such as the development of acute cauda equina syndrome, should likely be treated with urgent surgical decompression.

The Role of Intraoperative Navigation in Orthopaedic Surgery.

An orthopaedic surgeon's knowledge of anatomical landmarks is crucial, but other modalities supplement this by providing guidance and feedback to a surgeon. Advances in imaging have enabled three-dimensional visualization of the surgical field and patient anatomy, whereas advances in computer technology have allowed for real-time tracking of instruments and implants. Together, these innovations have given rise to intraoperative navigation systems. The authors review these advances in intraoperative navigation across orthopaedic subspecialties, focusing on the most recent evidence on patient outcomes and complications, the associated learning curve, and the effects on operative time, radiation exposure, and cost. In spine surgery, navigated pedicle screw placement may increase accuracy and safety, especially valuable when treating complex deformities. Improved accuracy of pelvic and peri-articular tumor resection and percutaneous fixation of acetabular and femoral neck fractures has also been achieved using navigation. Early applications in arthroscopy have included surface-based registration for tunnel positioning for anterior cruciate ligament reconstruction and osteochondroplasty for femoro-acetabular impingement. Navigated arthroplasty techniques have addressed knee gap balancing and mechanical axis restoration as well as acetabular cup and glenoid baseplate positioning. Among these orthopaedic subspecialties, significant variation is found in the clinical relevance and dedication to research of navigation techniques.

Substance P Receptor Antagonist Suppresses Inflammatory Cytokine Expression in Human Disc Cells.

STUDY DESIGN: Laboratory study. OBJECTIVE: To evaluate whether blockade of the Substance P (SP) NK1R attenuates its proinflammatory effect on human intervertebral disc cells (IVD), and to evaluate the signaling pathways associated with SP. SUMMARY OF BACKGROUND DATA: SP and its receptors are expressed in human IVD cells, and cause upregulation of inflammatory mediators; however, the effects of blocking these receptors have not been studied in human IVD cells. METHODS: Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were expanded in monolayer, and then suspended in alginate beads. The alginate beads were treated with culture medium first containing a high affinity NK1R antagonist (L-760735) at different concentrations, and then with medium containing both NK1R antagonist and SP at 2 concentrations. Ribonucleic acid was isolated and transcribed into cDNA. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate expression of interleukin (IL)-1ß, IL-6, and IL-8. Western blot analysis was performed to examine levels of the phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB p65). The cells were pretreated with specific inhibitors of p38 (SB203580), ERK1/2 (PD98059), and p65 (SM7368) and then stimulated with SP. RESULTS: We detected expression of NK1R, neurokinin receptor 2 (NK2R), and neurokinin receptor 3 (NK3R) in AF and NP cells. Treatment of disc cells with the NK1R antagonist was able to suppress expression of IL-1ß, IL-6, and IL-8 in a dose-dependent manner. SP stimulation increased phosphorylation of p38-MAPK and ERK1/2, but not of NFκB p65. This indicates that p38-MAPK and ERK1/2 control SP-induced cytokine expression independently from NF-kB p65. Inhibition of p38 and ERK1/2 activation reduced SP-induced IL-6 production in human disc cells. CONCLUSION: NK1R is responsible for the proinflammatory effect of SP on IVD cells and this effect can be blocked by preventing binding of SP to NK1R. This study shows for the first time that SP mediates signaling in disc cells through NK1R and that SP activates the proinflammatory p38-MAPK and ERK1/2 pathways. LEVEL OF EVIDENCE: 4.

Differential gene expression in anterior and posterior annulus fibrosus.

STUDY DESIGN: Laboratory study. OBJECTIVE: To evaluate the differential gene expression of cytokines and growth factors in anterior versus posterior annulus fibrosus (AF) intervertebral disc (IVD) specimens. SUMMARY OF BACKGROUND DATA: Histological analysis has demonstrated regional differences in vascular and neural ingrowth in the IVD, and similar differences may exist for cytokine and growth factor expression in patients with degenerative disc disease (DDD). Regional expression of these cytokines may also be related to the pain experienced in DDD. METHODS: IVD tissue was obtained from patients undergoing anterior lumbar interbody fusion surgery for back pain with radiological evidence of disc degeneration. For a control group, the discs of patients undergoing anterior lumbar discectomy for degenerative scoliosis were obtained as well. The tissue was carefully removed and separated into anterior and posterior AF. After tissue processing, an antibody array was completed to determine expression levels of 42 cytokines and growth factors. RESULTS: Nine discs from 7 patients with DDD and 5 discs from 2 patients with scoliosis were analyzed. In the DDD group, there were 10 cytokines and growth factors with significantly increased expression in the posterior AF versus the anterior AF ([interleukin] IL-4, IL-5, IL-6, M-CSF, MDC, tumor necrosis factor ß, EGF, IGF-1, angiogenin, leptin). In the scoliosis group, only angiogenin and PDGF-BB demonstrated increased expression in the posterior AF. No cytokines or growth factors had increased expression in the anterior AF compared with posterior AF. CONCLUSION: The posterior AF expresses increased levels of cytokines and growth factors compared with the anterior AF in patients with DDD. This differential expression may be important for targeting treatment of painful IVDs. LEVEL OF EVIDENCE: N/A.

Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells.

BACKGROUND: Cardiovascular progenitor cells (CPCs) have been identified within the developing mouse heart and differentiating pluripotent stem cells by intracellular transcription factors Nkx2.5 and Islet 1 (Isl1). Study of endogenous and induced pluripotent stem cell (iPSC)-derived CPCs has been limited due to the lack of specific cell surface markers to isolate them and conditions for their in vitro expansion that maintain their multipotency. METHODOLOGY/PRINCIPAL FINDINGS: We sought to identify specific cell surface markers that label endogenous embryonic CPCs and validated these markers in iPSC-derived Isl1(+)/Nkx2.5(+) CPCs. We developed conditions that allow propagation and characterization of endogenous and iPSC-derived Isl1(+)/Nkx2.5(+) CPCs and protocols for their clonal expansion in vitro and transplantation in vivo. Transcriptome analysis of CPCs from differentiating mouse embryonic stem cells identified a panel of surface markers. Comparison of these markers as well as previously described surface markers revealed the combination of Flt1(+)/Flt4(+) best identified and facilitated enrichment for Isl1(+)/Nkx2.5(+) CPCs from embryonic hearts and differentiating iPSCs. Endogenous mouse and iPSC-derived Flt1(+)/Flt4(+) CPCs differentiated into all three cardiovascular lineages in vitro. Flt1(+)/Flt4(+) CPCs transplanted into left ventricles demonstrated robust engraftment and differentiation into mature cardiomyocytes (CMs). CONCLUSION/SIGNIFICANCE: The cell surface marker combination of Flt1 and Flt4 specifically identify and enrich for an endogenous and iPSC-derived Isl1(+)/Nkx2.5(+) CPC with trilineage cardiovascular potential in vitro and robust ability for engraftment and differentiation into morphologically and electrophysiologically mature adult CMs in vivo post transplantation into adult hearts.