Does Bone Morphogenetic Protein Use Reduce Pseudarthrosis Rates in Single-Level Transforaminal Lumbar Interbody Fusion Surgeries?

BACKGROUND: Recombinant human bone morphogenetic protein 2 (rhBMP-2, or BMP for short) is a popular biological product used in spine surgeries to promote fusion and avoid the morbidity associated with iliac crest autograft. BMP's effect on pseudarthrosis in transforaminal lumbar interbody fusion (TLIF) remains unknown. OBJECTIVE: To assess the rates of pseudarthrosis in single-level TLIF with and without concurrent use of BMP. METHODS: This was a retrospective cohort study conducted at a single academic institution. Adults undergoing primary single-level TLIF with a minimum of 1 year of clinical and radiographic follow-up were included. BMP use was determined by operative notes at index surgery. Non-BMP cases with iliac crest bone graft were excluded. Pseudarthrosis was determined using radiographic and clinical evaluation. Bivariate differences between groups were assessed by independent t test and χ 2 analyses, and perioperative characteristics were analyzed by multiple logistic regression. RESULTS: One hundred forty-eight single-level TLIF patients were included. The mean age was 59.3 years, and 52.0% were women. There were no demographic differences between patients who received BMP and those who did not. Pseudarthrosis rates in patients treated with BMP were 6.2% vs 7.5% in the no BMP group (P = 0.756). There was no difference in reoperation for pseudarthrosis between patients who received BMP (3.7%) vs those who did not receive BMP (7.5%, P = 0.314). Patients who underwent revision surgery for pseudarthrosis more commonly had diabetes with end-organ damage (revised 37.5% vs not revised 1.4%, P < 0.001). Multiple logistic regression analysis demonstrated no reduction in reoperation for pseudarthrosis related to BMP use (OR 0.2, 95% CI 0.1-3.7, P = 0.269). Diabetes with end-organ damage (OR 112.6,95% CI 5.7-2225.8, P = 0.002) increased the risk of reoperation for pseudarthrosis. CONCLUSIONS: BMP use did not reduce the rate of pseudarthrosis or the number of reoperations for pseudarthrosis in single-level TLIFs. Diabetes with end-organ damage was a significant risk factor for pseudarthrosis. CLINICAL RELEVANCE: BMP is frequently used "off-label" in transforaminal lumbar interbody fusion; however, little data exists to demonstrate its safety and efficacy in this procedure.

External Validation of the National Surgical Quality Improvement Program Calculator Utilizing a Single Institutional Experience for Adult Spinal Deformity Corrective Surgery.

BACKGROUND: Identify the external applicability of the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) risk calculator in the setting of adult spinal deformity (ASD) and subsets of patients based on deformity and frailty status. METHODS: ASD patients were isolated in our single-center database and analyzed for the shared predictive variables displayed in the NSQIP calculator. Patients were stratified by frailty (not frail <0.03, frail 0.3-0.5, severely frail >0.5), deformity [T1 pelvic angle (TPA) > 30, pelvic incidence minus lumbar lordosis (PI-LL) > 20], and reoperation status. Brier scores were calculated for each variable to validate the calculator's predictability in a single center's database (Quality). External validity of the calculator in our ASD patients was assessed via Hosmer-Lemeshow test, which identified whether the differences between observed and expected proportions are significant. RESULTS: A total of 1606 ASD patients were isolated from the Quality database (48.7 years, 63.8% women, 25.8 kg/m2); 33.4% received decompressions, and 100% received a fusion. For each subset of ASD patients, the calculator predicted lower outcome rates than what was identified in the Quality database. The calculator showed poor predictability for frail, deformed, and reoperation patients for the category "any complication" because they had Brier scores closer to 1. External validity of the calculator in each stratified patient group identified that the calculator was not valid, displaying P values >0.05. CONCLUSION: The NSQIP calculator was not a valid calculator in our single institutional database. It is unable to comment on surgical complications such as return to operating room, surgical site infection, urinary tract infection, and cardiac complications that are typically associated with poor patient outcomes. Physicians should not base their surgical plan solely on the NSQIP calculator but should consider multiple preoperative risk assessment tools.

Multidisciplinary conference for complex surgery leads to improved quality and safety.

INTRODUCTION: Complex surgery for adult spinal deformity has high rates of complications, reoperations, and readmissions. Preoperative discussions of high-risk operative spine patients at a multidisciplinary conference may contribute to decreased rates of these adverse outcomes through appropriate patient selection and surgical plan optimization. With this goal, we implemented a high-risk case conference involving orthopedic and neurosurgery spine, anesthesia, intraoperative monitoring neurology, and neurological intensive care. METHODS: Included in this retrospective review were patients ≥ 18 years old meeting one of the following high-risk criteria: 8 + levels fused, osteoporosis with 4 + levels fused, three column osteotomy, anterior revision of the same lumbar level, or planned significant correction for severe myelopathy, scoliosis (> 75˚), or kyphosis (> 75˚). Patients were categorized as Before Conference (BC): surgery before 2/19/2019 or After Conference (AC): surgery after 2/19/2019. Outcome measures include intraoperative and postoperative complications, readmissions, and reoperations. RESULTS: 263 patients were included (96 AC, 167 BC). AC was older than BC (60.0 vs 54.6, p = 0.025) and had lower BMI (27.1 vs 28.9, p = 0.047), but had similar CCI (3.2 vs 2.9 p = 0.312), and ASA Classification (2.5 vs 2.5, p = 0.790). Surgical characteristics, including levels fused (10.6 vs 10.7, p = 0.839), levels decompressed (1.29 vs 1.25, p = 0.863), 3 column osteotomies (10.4% vs 18.6%, p = 0.080), anterior column release (9.4% vs 12.6%, p = 0.432), and revision cases (53.1% vs 52.4%, p = 0.911) were similar between AC and BC. AC had lower EBL (1.1 vs 1.9L, p < 0.001) and fewer total intraoperative complications (16.7% vs 34.1%, p = 0.002), including fewer dural tears (4.2% vs 12.6%, p = 0.025), delayed extubations (8.3% vs 22.8%%, p = 0.003), and massive blood loss (4.2% vs 13.2%, p = 0.018). Length of stay (LOS) was similar between groups (7.2 vs 8.2 days, 0.251). AC had a lower incidence of deep surgical site infections (SSI, 1.0% vs 6.6%, p = 0.038), but a higher rate of hypotension requiring vasopressor therapy (18.8% vs 4.8%, p < 0.001). Other postoperative complications were similar between groups. AC had lower rates of reoperation at 30 (2.1% vs 8.4%, p = 0.040) and 90 days (3.1 vs 12.0%, p = 0.014) and lower readmission rates at 30 (3.1% vs 10.2%, p = 0.038) and 90 days (6.3 vs 15.0%, p = 0.035). On logistic regression, AC patients had higher odds of hypotension requiring vasopressor therapy and lower odds of delayed extubation, intraoperative RBC, and intraoperative salvage blood. CONCLUSIONS: Following implementation of a multidisciplinary high-risk case conference, 30- and 90-day reoperation and readmission rates, intraoperative complications, and postoperative deep SSIs decreased. Hypotensive events requiring vasopressors increased, but did not result in longer LOS or greater readmissions. These associations suggest a multidisciplinary conference may help improve quality and safety for high-risk spine patients. particularly through minimizing complications and optimizing outcomes in complex spine surgery.

Comparative Analysis of Inpatient Opioid Consumption Between Different Surgical Approaches Following Single Level Lumbar Spinal Fusion Surgery.

STUDY DESIGN: Single-center retrospective cohort study. OBJECTIVES: To evaluate inpatient MME administration associated with different lumbar spinal fusion surgeries. METHODS: Patients ≥18 years of age with a diagnosis of Grade I or II spondylolisthesis, stenosis, degenerative disc disease or pars defect who underwent one-level Transforaminal Lumbar Interbody Fusion (TLIF) or one-level Anterior Lumbar Interbody Fusion (ALIF) or Lateral Lumbar Interbody Fusion (LLIF) through traditional MIS, anterior-posterior position or single position approaches between L2-S1. Outcome measures included patient demographics, surgical procedure and approach, perioperative clinical characteristics, incidence of ileus and inpatient MME. Statistical analysis included one-way ANOVA with a post-hoc Tukey Test and Kruskal-Wallis Test with post-hoc Mann-Whitney test. MME was calculated as per the Centers for Medicare and Medicaid Services and previous literature. Significance set at P < .05. RESULTS: Mean age differed significantly between MIS TLIF (55.6 ± 12.5 years) and all other groups (Open TLIF 57.1 ± 12.5, SP ALIF/LLIF 57.9 ± 9.9, TP ALIF/LLIF 50.9 ± 12.7, Open ALIF/LLIF 58.4 ± 15.5). MIS TLIF had the shortest LOS compared to all groups except SP ALIF/LLIF. Total MME was significantly different between MIS TLIF and Open ALIF/LLIF (172.5 MME vs 261.1 MME, P = .044) as well as MIS TLIF and TP ALIF/LLIF (172.5 MME vs 245.4 MME, P = .009). There were no significant differences in MME/hour and incidence of ileus between all groups. CONCLUSION: Patients undergoing MIS TLIF had lower inpatient opioid intake compared to TP and SP ALIF/LLIF, as well as shorter LOS compared to all groups except SP ALIF/LLIF. Thus, it appears that the advantages of minimally invasive surgery are seen in minimally invasive TLIFs.

Incidence of dysphagia following posterior cervical spine surgery.

Abundant literature exists describing the incidence of dysphagia following anterior cervical surgery; however, there is a paucity of literature detailing the incidence of dysphagia following posterior cervical procedures. Further characterization of this complication is important for guiding clinical prevention and management. Patients ≥ 18 years of age underwent posterior cervical fusion with laminectomy or laminoplasty between C1-T1. Pre- and post-operative dysphagia was assessed by a speech language pathologist. The patient cohort was categorized by approach: Laminectomy + Fusion (LF) and Laminoplasty (LP). Patients were excluded from radiographic analyses if they did not have both baseline and follow-up imaging. The study included 147 LF and 47 LP cases. There were no differences in baseline demographics. There were three patients with new-onset dysphagia in the LF group (1.5% incidence) and no new cases in the LP group (p = 1.000). LF patients had significantly higher rates of post-op complications (27.9% LF vs. 8.5% LP, p = 0.005) but not intra-op complications (6.1% LF vs. 2.1% LP, p = 0.456). Radiographic analysis of the entire cohort showed no significant changes in cervical lordosis, cSVA, or T1 slope. Both group comparisons showed no differences in incidence of dysphagia pre and post operatively. Based on this study, the likelihood of developing dysphagia after LF or LP are similarly low with a new onset dysphagia rate of 1.5%.

Fusing to the Sacrum/Pelvis: Does the Risk of Reoperation in Thoracolumbar Fusions Depend on Upper Instrumented Vertebrae (UIV) Selection?

BACKGROUND: There is controversy as to whether fusions should have the upper instrumented vertebrae (UIV) end in the upper lumbar spine or cross the thoracolumbar junction. This study compares outcomes and reoperation rates for thoracolumbar fusions to the sacrum or pelvis with UIV in the lower thoracic versus lumbar spine to determine if there is an increased reoperation rate depending on UIV selection. METHODS: A retrospective review of prospectively collected data was conducted from a single-center database on adult patients with degeneration and deformity who underwent primary and revision fusions with a caudal level of S1 or ilium between 2012 and 2018. Fusions were classified as anterior, posterior, or combination approach. Revision fusions included patients who had spinal surgery at another institution prior to their revision surgery at the center. Patients were categorized into 1 of 3 groups based on UIV: T9-T11, upper lumbar region (L1-L2), and lower lumbar region (L3-L5). Inclusion criteria were age 18 years or older and at least 1 year of clinical follow-up. Patients were excluded from analysis if they had tumors, infections, or less than 1 year of follow-up after the index procedure. RESULTS: The reoperation rates for the UIV groups in the thoracic (28%) and upper lumbar (27%) spine were nearly equal in magnitude and were both significantly higher than the reoperation rate in the lower lumbar group (18%, P = .046). Reoperation for the diagnosis of adjacent segment disease was 8.3% in the upper lumbar spine and statistically significantly higher than the reoperation rates for adjacent segment disease in the thoracic (1%) or lower lumbar (4.5%, P = .042) spine. Reoperations for pseudoarthrosis and proximal junctional kyphosis were 13% and 4%, respectively, in the thoracic spine, both of which were statistically significantly different (pseudoarthrosis, P = .035; proximal junctional kyphosis, P = .002) from the reoperation rates for the same diagnoses in the upper lumbar spine (4.6% and 1%) or lower lumbar spine (6.2% and 0%). A multivariate logistical regression model at 2-year follow up did not show a statistically significant difference between reoperation rates between the thoracic and upper lumbar spine UIV groups. CONCLUSION: Constructs with UIV in the thoracic spine suffer from higher rates of proximal junctional kyphosis and pseudoarthrosis, whereas those with UIV in the upper lumbar spine have higher rates of adjacent segment disease. Given this tradeoff, there is no certain recommendation on what UIV will result in a lower reoperation rate in thoracolumbar fusion constructs to the sacrum or pelvis. Surgeons must evaluate patient characteristics and risks to make the optimal decision.

Comparison of Plastic Surgeon and Spine Surgeon Closure in Revision Short Segment Thoracolumbar Spinal Fusions.

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: To compare outcomes of plastic versus spine surgeon wound closure in revision 1 to 4 level thoracolumbar fusions. SUMMARY OF BACKGROUND DATA: Plastic surgeons perform layered musculocutaneous flap closures in high-risk spine patients such as revision posterior spinal fusion and complex deformity correction surgeries. Few studies have assessed outcomes of revision fusion performed with plastic surgical closures, particularly in nondeformity thoracolumbar spinal surgery. METHODS: A retrospective review of 1 to 4 level revision thoracolumbar fusion performed by Orthopedic or Neurosurgical spine surgeons. Patient charts were reviewed for demographics and perioperative outcomes. Patients were divided into two cohorts: wound closures performed by spine surgeons and those closed by plastic surgeons. Outcomes were analyzed before and after propensity score match for prior levels fused, iliac fixation, and levels fused at index surgery. Significance was set at P < 0.05. RESULTS: Three hundred fifty-seven (87.3%) spine surgeon (SS) and 52 (12.7%) plastic surgeon (PS) closures were identified. PS group had significantly higher number of levels fused at index (PS 2.7 ±â€Š1.0 vs. SS 1.8 ±â€Š0.9, P < 0.001) and at prior surgeries (PS 1.8 ±â€Š1.2 vs. SS 1.0 ±â€Š0.9, P < 0.001), and rate of iliac instrumentation (PS 17.3% vs. SS 2.8%, P < 0.001). Plastics closure was an independent risk factor for length of stay  > 5 days (odds ratio 2.3) and postoperative seroma formation (odds ratio 7.8). After propensity score match, PS had higher rates of seromas (PS 36.5% vs. SS 3.8%, P < 0.001). There were no differences between PS and SS groups in surgical outcomes, perioperative complication, surgical site infection, seroma requiring aspiration, or return to operating room at all time points until follow-up (P > 0.05 for all). CONCLUSION: Plastic spinal closure for 1 to 4 level revision posterior thoracolumbar fusions had no advantage in reducing wound complications over spine surgeon closure but increased postoperative seroma formation.Level of Evidence: 4.

COVID-19 pandemic and elective spinal surgery cancelations - what happens to the patients?

BACKGROUND CONTEXT: The COVID-19 pandemic caused nationwide suspensions of elective surgeries due to reallocation of resources to the care of COVID-19 patients. Following resumption of elective cases, a significant proportion of patients continued to delay surgery, with many yet to reschedule, potentially prolonging their pain and impairment of function and causing detrimental long-term effects. PURPOSE: The aim of this study was to examine differences between patients who have and have not rescheduled their spine surgery procedures originally cancelled due to the COVID-19 pandemic, and to evaluate the reasons for continued deferment of spine surgeries even after the lifting of the mandated suspension of elective surgeries. STUDY DESIGN/SETTING: Retrospective case series at a single institution PATIENT SAMPLE: Included were 133 patients seen at a single institution where spine surgery was canceled due to a state-mandated suspension of elective surgeries from March to June, 2020. OUTCOME MEASURES: The measures assessed included preoperative diagnoses and neurological dysfunction, surgical characteristics, reasons for surgery deferment, and PROMIS scores of pain intensity, pain interference, and physical function. METHODS: Patient electronic medical records were reviewed. Patients who had not rescheduled their canceled surgery as of January 31, 2021, and did not have a reason noted in their charts were called to determine the reason for continued surgery deferment. Patients were divided into three groups: early rescheduled (ER), late rescheduled (LR), and not rescheduled (NR). ER patients had a date of surgery (DOS) prior to the city's Phase 4 reopening on July 20, 2020; LR patients had a DOS on or after that date. Statistical analysis of the group findings included analysis of variance with Tukey's honestly significant difference (HSD) post-hoc test, independent samples T-test, and chi-square analysis with significance set at p≤.05. RESULTS: Out of 133 patients, 47.4% (63) were in the ER, 15.8% (21) in the LR, and 36.8% (49) in the NR groups. Demographics and baseline PROMIS scores were similar between groups. LR had more levels fused (3.6) than ER (1.6), p= .018 on Tukey HSD. NR (2.1) did not have different mean levels fused than LR or ER, both p= >.05 on Tukey HSD. LR had more three column osteotomies (14.3%) than ER and (1.6%) and NR (2.0%) p=.022, and fewer lumbar microdiscectomies (0%) compared to ER (20.6%) and NR (10.2%), p=.039. Other surgical characteristics were similar between groups. LR had a longer length of stay than ER (4.2 vs 2.4, p=.036). No patients in ER or LR had a nosocomial COVID-19 infection. Of NR, 2.0% have a future surgery date scheduled and 8.2% (4) are acquiring updated exams before rescheduling. 40.8% (20; 15.0% total cohort) continue to defer surgery over concern for COVID-19 exposure and 16.3% (8) for medical comorbidities. 6.1% (3) permanently canceled for symptom improvement. 8.2% (4) had follow-up recommendations for non-surgical management. 4.1% (2) are since deceased. CONCLUSION: Over 1/3 of elective spine surgeries canceled due to COVID-19 have not been performed in the 8 months from when elective surgeries resumed in our institution to the end of the study. ER patients had less complex surgeries planned than LR. NR patients continue to defer surgery primarily over concern for COVID-19 exposure. The toll on the health of these patients as a result of the delay in treatment and on their lives due to their inability to return to normal function remains to be seen.

Expandable cages increase the risk of intraoperative subsidence but do not improve perioperative outcomes in single level transforaminal lumbar interbody fusion.

BACKGROUND CONTEXT: Expandable cages (EXP) are being more frequently utilized in transforaminal lumbar interbody fusions (TLIF). EXP were designed to reduce complications related to neurological retraction, enable better lordosis restoration, and improve ease of insertion, particularly in the advent of minimally invasive surgical (MIS) techniques, however they are exponentially more expensive than the nonexpandable (NE) alternative. PURPOSE: To investigate the clinical results of expandable cages in single level TLIF. STUDY DESIGN/SETTING: Retrospective review at a single institution. PATIENT SAMPLE: Two hundred and fifty-two single level TLIFs from 2012 to 2018 were included. OUTCOME MEASURES: Clinical characteristics, perioperative and neurologic complication rates, and radiographic measures. METHODS: Patients ≥18 years of age who underwent single level TLIF with minimum 1 year follow-up were included. OUTCOME MEASURES: clinical characteristics, perioperative and neurologic complications. Radiographic analysis included pelvic incidence-lumbar lordosis (PI-LL) mismatch, segmental lumbar lordosis (LL) mismatch, disc height restoration, and subsidence ≥2 mm. Statistical analysis included independent t tests and chi-square analysis. For nonparametric variables, Mann-Whitney U test and Spearman partial correlation were utilized. Multivariate regression was performed to assess relationships between surgical variables and recorded outcomes. For univariate analysis significance was set at p<.05. Due to the multiple comparisons being made, significance for regressions was set at p<.025 utilizing Bonferroni correction. RESULTS: Two hundred and fifty-two TLIFs between 2012 and 2018 were included, with 152 NE (54.6% female, mean age 59.28±14.19, mean body mass index (BMI) 28.65±5.38, mean Charlson Comorbidity Index (CCI) 2.20±1.89) and 100 EXP (48% female, mean age 58.81±11.70, mean BMI 28.68±6.06, mean CCI 1.99±1.66) with no significant differences in demographics. Patients instrumented with EXP cages had a shorter length of stay (3.11±2.06 days EXP vs. 4.01±2.64 days NE; Z=-4.189, p<.001) and a lower estimated blood loss (201.31±189.41 mL EXP vs. 377.82±364.06 mL NE; Z=-6.449, p<.001). There were significantly more MIS-TLIF cases and bone morphogenic protein (BMP) use in the EXP group (88% MIS, p<.001 and 60% BMP, p<.001) as illustrated in Table 1. There were no significant differences between the EXP and NE groups in rates of radiculitis and neuropraxia. In multivariate regression analysis, EXP were not associated with a difference in perioperative outcomes or complications. Radiographic analyses demonstrated that the EXP group had a lower PI-LL mismatch than the NE cage group at baseline (3.75±13.81° EXP vs. 12.75±15.81° NE; p=.001) and at 1 year follow-up (3.81±12.84° EXP vs. 8.23±12.73° NE; p=.046), but change in regional and segmental alignment was not significantly different between groups. Multivariate regression demonstrated that EXP use was a risk factor for intraoperative subsidence (2.729[1.185-6.281]; p=.018). CONCLUSIONS: Once technique was controlled for, TLIFs utilizing EXP do not have significantly improved neurologic or radiographic outcomes compared with NE. EXP increase risk of intraoperative subsidence. These results question the value of the EXP given the higher cost.

Protease signaling regulates apical cell extrusion, cell contacts, and proliferation in epithelia.

Mechanisms that sense and regulate epithelial morphogenesis, integrity, and homeostasis are incompletely understood. Protease-activated receptor 2 (Par2), the Par2-activating membrane-tethered protease matriptase, and its inhibitor, hepatocyte activator inhibitor 1 (Hai1), are coexpressed in most epithelia and may make up a local signaling system that regulates epithelial behavior. We explored the role of Par2b in matriptase-dependent skin abnormalities in Hai1a-deficient zebrafish embryos. We show an unexpected role for Par2b in regulation of epithelial apical cell extrusion, roles in regulating proliferation that were opposite in distinct but adjacent epithelial monolayers, and roles in regulating cell-cell junctions, mobility, survival, and expression of genes involved in tissue remodeling and inflammation. The epidermal growth factor receptor Erbb2 and matrix metalloproteinases, the latter induced by Par2b, may contribute to some matriptase- and Par2b-dependent phenotypes and be permissive for others. Our results suggest that local protease-activated receptor signaling can coordinate cell behaviors known to contribute to epithelial morphogenesis and homeostasis.

Mapping inhibitor binding modes on an active cysteine protease via nuclear magnetic resonance spectroscopy.

Cruzain is a member of the papain/cathepsin L family of cysteine proteases, and the major cysteine protease of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We report an autoinduction methodology that provides soluble cruzain in high yields (>30 mg/L in minimal medium). These increased yields provide sufficient quantities of active enzyme for use in nuclear magnetic resonance (NMR)-based ligand mapping. Using circular dichroism and NMR spectroscopy, we also examined the solution-state structural dynamics of the enzyme in complex with a covalently bound vinyl sulfone inhibitor (K777). We report the backbone amide and side chain carbon chemical shift assignments of cruzain in complex with K777. These resonance assignments were used to identify and map residues located in the substrate binding pocket, including the catalytic Cys25 and His162. Selective [(15)N]Cys, [(15)N]His, and [(13)C]Met labeling was performed to quickly assess cruzain-ligand interactions for a set of eight low-molecular weight compounds exhibiting micromolar binding or inhibition. Chemical shift perturbation mapping verified that six of the eight compounds bind to cruzain at the active site. Three different binding modes were delineated for the compounds, namely, covalent, noncovalent, and noninteracting. These results provide examples of how NMR spectroscopy can be used to screen compounds for fast evaluation of enzyme-inhibitor interactions to facilitate lead compound identification and subsequent structural studies.