Application of nonpenetrating titanium clips for primary spinal dural closure following intradural tethered cord release in pediatric tethered cord syndrome: Profile of safety, efficacy, efficiency, and complications.

Introduction: Surgical treatment for tethered cord syndrome (TCS) involves a laminotomy for intradural lysis of filum terminale (LFT), with the goal of releasing excess tension on the conus medullaris by dividing the filum terminale. While LFT alleviates clinical symptoms, it is associated with risks and complications, including cerebrospinal fluid (CSF) leak and infection, either superficial or deep. Some risks and complications of LFT relate to efficiency and quality of primary dural closure and its downstream effects. We sought to assess the utility of nonpenetrating titanium clips (TC) for primary dural closure with a particular focus on operative duration, associated costs, and complication profiles in a series of pediatric patients undergoing LFT, hypothesizing that TC utilization leads to more efficient closure and therefore potentially lower costs and potentially associated anesthetic length and risks. Methods: A 4-surgeon, single institution series of 28 pediatric patients underwent LFT with subsequent dural closure performed with either the AnastoClip® nonpenetrating titanium clips or traditional suture technique between July 2022 and May 2023. In order to compare the safety, efficacy, and cost-effectiveness between the two dural closure techniques, relevant data were collected including patient demographics and rates of CSF leak, infection at three-month follow-up, and reoperation. Operative durations and times from beginning to end of dural closure were recorded. Results: A total of 28 pediatric patients (mean age: 5.9 years, 43% female, range: 0.71-17 years) with TCS underwent LFT. All patients underwent procedures involving intradural surgery of the lumbar region. Dural closure was performed using traditional suturing in 19 patients (67.9%) and TC in 9 (32.1%). With respect to duration of dural closure, the average time to closure using traditional suturing techniques was 1271 s (or 21 min and 11 s), while the average time for TC was 265 s (or 4 min and 25 s). At three-month follow-up, one case of cerebrospinal fluid (CSF) leak or infection was observed in the suture cohort and required reoperation. Conclusion: Clinical outcomes in the TC group were excellent, consistent with previous reports; our findings further suggest that TCs result in more efficient dural closure than traditional suturing techniques. Our findings suggest that TC may be a safe, efficacious, and more efficient alternative to traditional suture for achieving dural closure in pediatric patients with TCS undergoing LFT surgery.

Impact of State Laws on Dispensing Opioid Prescriptions Following Posterior Lumbar Interbody Fusion Procedures: A Retrospective Large National Database Study.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: This study aimed to examine the effect of state legislation on prescribing behavior after a commonly performed spinal procedure, posterior lumbar interbody fusion (PLIF). METHODS: Two cohorts of patients from the Pearl Diver Database were created based on patients who underwent PLIF surgery in 2014-15 and 2018-19. We compared opioid prescription rates and morphine-milli-equivalent (MME) between states with and without prescription legislation. RESULTS: We analyzed 50 958 PLIF patients from 2014-15 and 46 751 patients from 2018-19. Among them, 38 states passed opioid prescription laws in 2016-2017, while 12 states did not. The percentage of patients receiving opioid prescriptions within 365 days post-surgery remained similar in both time periods (49% in 2014-15 and 48% in 2018-2019). This trend was consistent across states with and without prescription legislation (50% vs 48% in 2014-2015, and similar in 2018-19). Opioid prescription quantity significantly decreased in all states between 2014-15 and 2018-19. In states with legislation, average MME dropped from 9198 ± 21 002 to 4932 ± 13 213 (46.4% decrease), and in states without legislation, it decreased from 9175 ± 21 032 to 4994 ± 11 687 (45.6% decrease). However, these differences were not statistically significant (P = .7985). CONCLUSION: From 2014 to 2018, there was a significant decrease in the number of opioids prescribed after PLIF. However, this decrease occurred irrespective of state legislation on prescribing practices being passed. We believe the reduction in opioids prescribed was due to increased awareness surrounding the dangers of opioids among physicians.

Evaluating Surgical Cervical Arthrodesis With a Novel MRI Grading Score.

STUDY DESIGN: This was a single-institution retrospective study. OBJECTIVE: Evaluate a magnetic resonance imaging (MRI)-scoring system to differentiate arthrodesis from pseudoarthrosis following anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: Diagnostic workup following fusion surgery often includes MRI to evaluate neural structures and computed tomography (CT) and/or dynamic x-rays to evaluate instrumentation and arthrodesis. The use of MRI alone for these evaluations would protect patients from harmful CT and x-ray ionizing radiation. METHODS: Neurosurgical attending evaluated CTs for arthrodesis or pseudoarthrosis. Blinded neuroradiology attending and neurosurgery senior resident evaluated independent T1 and T2 region of interest (ROI) signal intensity over instrumented disk space. Cerebral spinal fluid (CSF) at the cisterna magnum and distal adjacent uninstrumented vertebral body (VB) were also calculated. ROI interspace /ROI CSF and ROI interspace /ROI VB quotients were used to create T1- and T2-interspace interbody scores (IIS). RESULTS: Study population (n=64 patients, 50% female) with a mean age of 51.72 years and 109 instrumented levels with 45 fused levels (41.3%) were included. T1-weighted MRI, median T1-IIS CSF for arthrodesis was 176.20 versus 130.92 for pseudoarthrosis ( P <0.0001), T1-IIS VB for arthrodesis was 68.52 and pseudoarthrosis was 52.71 ( P <0.0001). T2-weighted MRI, median T2-IIS CSF for arthrodesis was 27.72 and 14.21 for pseudoarthrosis ( P <0.0001), while T2-IIS VB for arthrodesis was 67.90 and 41.02 for pseudoarthrosis ( P <0.0001). The greatest univariable discriminative capability for arthrodesis via AUROC was T1-IIS VB (0.7743). CONCLUSION: We describe a novel MRI scoring system that may help determine arthrodesis versus pseudoarthrosis following anterior cervical discectomy and fusion. Postoperative symptomatic patients may only require MRI, which would protect patients from ionizing radiation. LEVEL OF EVIDENCE: Level IV.

Low-Cost Wound Healing Protocol Reduces Infection and Reoperation Rates After Cranioplasty: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Cranioplasty infections are a common and expensive problem associated with significant morbidity. Our objective was to determine whether a wound healing protocol after cranioplasty reduced the rate of infections and to determine the value of this intervention. METHODS: This is a single-institution retrospective chart review of 2 cohorts of cranioplasty patients over 12 years. The wound healing protocol, consisting of vitamin and mineral supplementation, fluid supplementation, and oxygen support, was instituted for all patients aged older than 15 years undergoing cranioplasty. We retrospectively reviewed the charts of all patients over the study period and compared outcomes before and after protocol institution. Outcomes included surgical site infection, return to operating room within 30 days, and cranioplasty explant. Cost data were collected from the electronic medical record. We included 291 cranioplasties performed before the wound healing protocol and 68 postprotocol. RESULTS: Baseline demographics and comorbidities were comparable between preprotocol and postprotocol groups. Odds of takeback to operating room within 30 days were the same before and after the wound healing protocol (odds ratio [OR] 2.21 [95% CI 0.76-6.47], P = .145). Odds of clinical concern for surgical site infection were significantly higher in the preprotocol group (OR 5.21 [95% CI 1.22-22.17], P = .025). Risk of washout was higher in the preprotocol group (HR 2.86 [95% CI 1.08-7.58], P = .035). Probability of cranioplasty flap explant was also significantly higher in the preprotocol group (OR 4.70 [95% CI 1.10-20.05], P = .036). The number needed to treat to prevent 1 cranioplasty infection was 24. CONCLUSION: A low-cost wound healing protocol was associated with reduced rate of infections after cranioplasty with concomitant reduction in reoperations for washout, saving the health care system more than $50,000 per 24 patients. Prospective study is warranted.

Utilization of Vertebroplasty/Kyphoplasty in the Management of Compression Fractures: National Trends and Predictors of Vertebroplasty/Kyphoplasty.

OBJECTIVE: The purpose of this study is to examine the utilization of kyphoplasty/vertebroplasty procedures in the management of compression fractures. With the growing elderly population and the associated increase in rates of osteoporosis, vertebral compression fractures have become a daily encounter for spine surgeons. However, there remains a lack of consensus on the optimal management of this patient population. METHODS: A retrospective analysis of 91 million longitudinally followed patients from 2016 to 2019 was performed using the PearlDiver Patient Claims Database. Patients with compression fractures were identified using International Classification of Disease, 10th Revision codes, and a subset of patients who received kyphoplasty/vertebroplasty were identified using Common Procedural Terminology codes. Baseline demographic and clinical data between groups were acquired. Multivariable regression analysis was performed to determine predictors of receiving kyphoplasty/vertebroplasty. RESULTS: A total of 348,457 patients with compression fractures were identified with 9.2% of patients receiving kyphoplasty/vertebroplasty as their initial treatment. Of these patients, 43.5% underwent additional kyphoplasty/vertebroplasty 30 days after initial intervention. Patients receiving kyphoplasty/vertebroplasty were significantly older (72.2 vs. 67.9, p < 0.05), female, obese, had active smoking status and had higher Elixhauser Comorbidity Index scores. Multivariable analysis demonstrated that female sex, smoking status, and obesity were the 3 strongest predictors of receiving kyphoplasty/vertebroplasty (odds ratio, 1.27, 1.24, and 1.14, respectively). The annual rate of kyphoplasty/vertebroplasty did not change significantly (range, 8%-11%). CONCLUSION: The majority of vertebral compression fractures are managed nonoperatively. However, certain patient factors such as smoking status, obesity, female sex, older age, osteoporosis, and greater comorbidities are predictors of undergoing kyphoplasty/vertebroplasty.

Risk Factors, Incidence and Mortality of Vertebral Artery Injury in Patients Undergoing Anterior Cervical Corpectomy: A Retrospective Large National Data Base Study.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: To determine the incidence of vertebral artery injury (VAI), risk factors, intervention, associated complications, and mortality in patients undergoing anterior cervical corpectomy. METHODS: We performed a retrospective review of the incidence of VAI during anterior cervical corpectomy using the PearlDiver database from 2010-2017. The CPT code 63 081 to identify corpectomy patients. Patient data extracted included, incidence of VAI, demographic factors, intervention, and future complications of death and stroke. The risk were calculated compared with those patients who did not have VAI. RESULTS: 26 126 patients were identified to have undergone cervical corpectomy. Multivariate analysis of risk factors showed that younger age and male sex were associate with higher rate of injury (t = -11.5; P < .0001 and t = 3.8; P = .0001, respectively). Vertebral artery injuries occurred in 78 patients at an incidence of .3%. 11 (14%) VAI patients had a cerebral infarction compared with 1705 (7%) for non-VAI patients (OR = 2.13; 95% CI = [1.18 - 3.85; P = .0179]) during the follow up period. 1-year mortality rates were higher in patients who suffered a VAI (14%) compared to those who did not suffer a VAI (4%; OR = 3.85; CI = [2.04 - 7.14]; P < .0001). CONCLUSION: Consequence of VAI may not be known for months following the injury. Although the same admission mortality is rare with this injury, there is a significant increase in post-discharge complications. This study suggests that further investigations into long term health risk of VAI is needed.

The Unfolded Protein Response Reveals eIF2α Phosphorylation as a Critical Factor for Direct MHC Class I Antigen Presentation.

The ability to modulate direct MHC class I (MHC I) Ag presentation is a desirable goal for the treatment of a variety of conditions, including autoimmune diseases, chronic viral infections, and cancers. It is therefore necessary to understand how changes in the cellular environment alter the cells' ability to present peptides to T cells. The unfolded protein response (UPR) is a signaling pathway activated by the presence of excess unfolded proteins in the endoplasmic reticulum. Previous studies have indicated that chemical induction of the UPR decreases direct MHC I Ag presentation, but the precise mechanisms are unknown. In this study, we used a variety of small molecule modulators of different UPR signaling pathways to query which UPR signaling pathways can alter Ag presentation in both murine and human cells. When signaling through the PERK pathway, and subsequent eIF2α phosphorylation, was blocked by treatment with GSK2656157, MHC I Ag presentation remain unchanged, whereas treatment with salubrinal, which has the opposite effect of GSK2656157, decreases both Ag presentation and overall cell-surface MHC I levels. Treatment with 4µ8C, an inhibitor of the IRE1α UPR activation pathway that blocks splicing of Xbp1 mRNA, also diminished MHC I Ag presentation. However, 4µ8C treatment unexpectedly led to an increase in eIF2α phosphorylation in addition to blocking IRE1α signaling. Given that salubrinal and 4µ8C lead to eIF2α phosphorylation and similar decreases in Ag presentation, we conclude that UPR signaling through PERK, leading to eIF2α phosphorylation, results in a modest decrease in direct MHC I Ag presentation.

Refractory CIDP: Clinical characteristics, antibodies and response to alternative treatment.

OBJECTIVE: To review the clinical characteristics, antibodies, and response to alternative treatments in a cohort of patients with refractory CIDP. METHODS: We reviewed the charts of all CIDP patients seen at the Oregon Health & Science University neuromuscular clinic between 2017 and 2019. We collected demographics, clinical characteristics, antibodies, and response to treatments. RESULTS: Among 45 CIDP patients studied, 34 (76%) showed improvement with first-line therapy (steroids, IVIG and/or plasmapheresis) and 11 (24%) were considered refractory to first line therapy. Of the latter, 7 of 11 patients (64%) responded to alternative treatment (cyclophosphamide or rituximab). Three were refractory to all treatment. Most patients were ambulatory without aid and a few were in remission. One patient died from complications of alcoholic liver cirrhosis. Thrombosis was seen in three patients receiving IVIG. Six patients (13%) tested positive for Neurofascin (NF) antibodies. Four tested positive for NF155 IgM antibodies only and of those, one responded to IVIG, two partially responded to IVIG and one was refractory. One patient tested positive for NF155 IgG4. Another tested positive for NF155 IgG4 and NF155 IgM. Both patients with IgG4 antibodies were refractory to IVIG, one responded to rituximab and one was refractory to all treatment. CONCLUSION: Less than a quarter of our CIDP patients did not respond to steroids, IVIG, and/or plasmapheresis. Most of the refractory patients responded to rituximab or cyclophosphamide. Patients with IgG4 NF antibodies were resistant to IVIG. The majority of refractory CIDP patients were seronegative and disease management relied on clinical judgement.

Analysis of acquired mutations in transgenes arising in Ba/F3 transformation assays: findings and recommendations.

The identification and functional validation of potentially oncogenic mutations in leukemia is an essential step toward a future of personalized targeted therapy. To assess the oncogenic capacity of individual mutations, reliable and scalable in vitro experimental approaches are required. Since 1988, researchers have used the IL-3 dependent Ba/F3 transformation assay to validate the oncogenic potential of mutations to drive factor-independent growth. Here we report a previously unrecognized phenomenon whereby Ba/F3 cells, engineered to express weakly transforming mutations, present with additional acquired mutations in the expressed transgene following factor withdrawal. Using four mutations with known transformative capacity in three cytokine receptors (CSF2RB, CSF3R and IL7R), we demonstrate that the mutated receptors are highly susceptible to acquiring additional mutations. These acquired mutations of unknown functional significance are selected by factor withdrawal but appear to exist prior to the removal of growth factor. This anomaly has the potential to confound efforts to both validate and characterize oncogenic mutations in leukemia, particularly when it is not standard practice to sequence validate cDNAs from transformed Ba/F3 lines. We present specific recommendations to detect and mitigate this phenomenon in future research using Ba/F3 transformation assays, along with methods to make the Ba/F3 assay more quantitative.