Association between timing of kyphoplasty and opioid prescribing risk after vertebral fracture.

OBJECTIVE: Approximately 550,000 Americans experience vertebral fracture annually, and most receive opioids to treat the resulting pain. Kyphoplasty of the fractured vertebra is a procedural alternative that may mitigate risks of even short-term opioid use. While reports of kyphoplasty's impact on pain scores are mixed, no large-scale data exist regarding opioid prescribing before and after the procedure. This study was conducted to determine whether timing of kyphoplasty following vertebral fracture is associated with duration or intensity of opioid prescribing. METHODS: This retrospective cohort study used 2001-2014 insurance claims data from a single, large private insurer in the US across multiple care settings. Patients were adults with vertebral fractures who were prescribed opioids and underwent balloon-assisted kyphoplasty within 4 months of fracture. Opioid overdose risk was stratified by prescribed average daily morphine milligram equivalents using CDC guidelines. Filled prescriptions and risk categories were evaluated at baseline and 90 days following kyphoplasty. RESULTS: Inclusion criteria were met by 7119 patients (median age 77 years, 71.7% female). Among included patients, 3505 (49.2%) were opioid naïve before fracture. Of these patients, 31.1% had new persistent opioid prescribing beyond 90 days after kyphoplasty, and multivariable logistic regression identified kyphoplasty after 8 weeks as a predictor (OR 1.34, 95% CI 1.02-1.76). For patients previously receiving opioids, kyphoplasty > 4 weeks after fracture was associated with persistently elevated prescribing risk (OR 1.84, 95% CI 1.23-2.74). CONCLUSIONS: New persistent opioid prescribing occurred in nearly one-third of patients undergoing kyphoplasty after vertebral fracture, although early treatment was associated with a reduction in this risk. For patients not naïve to opioids before fracture diagnosis, early kyphoplasty was associated with less persistent elevation of opioid overdose risk. Subsequent trials must compare opioid use by vertebral fracture patients treated via operative (kyphoplasty) and nonoperative (ongoing opioid) strategies before concluding that kyphoplasty lacks value, and early referral for kyphoplasty may be appropriate to avoid missing a window of efficacy.

Early initiation of chemoradiation following index craniotomy is associated with decreased survival in high-grade glioma.

The Stupp protocol of post-resection external beam radiation therapy and concomitant temozolomide is the standard of care for patients with newly-diagnosed glioblastoma, with expanded use in anaplastic astrocytoma. However, the optimal interval between surgery and these adjuvant therapies, and its impact on survival, is unknown. To investigate this, de-identified claims from a large, private health insurance database were queried to identify adult patients who underwent index craniotomy for resection of a supratentorial neoplasm during the period 2005-2014 and began postoperative radiation and temozolomide within 13 weeks of surgery. A total of 2535 patients were assigned to groups based on interval from surgery to first radiation treatment of up to 4 weeks, 4-6 weeks, or 6-13 weeks. Of these, 1098 patients began radiation treatment within 4 weeks of craniotomy, 1019 between 4 and 6 weeks, and 418 between 6 and 13 weeks. There was significant regional variation in treatment schedule in the United States. Survival was calculated based on time from first craniotomy to death. Kaplan-Meier plot and multivariate Cox proportional hazard regression demonstrated a statistically significant association between earliest postoperative radiation and decreased survival (hazard ratio 1.31), along with older age and male sex. Earlier initiation of postoperative radiation for high-grade glioma is not associated with increased survival. Rather, beginning radiation treatment within 4 weeks of craniotomy was associated with significantly worse survival compared to initiation of treatment 4-13 weeks after craniotomy. This is the largest population-based study to date regarding timing of Stupp protocol initiation.

Polysialic acid governs T-cell development by regulating progenitor access to the thymus.

Although the polysialyltransferase ST8Sia IV is expressed in both primary and secondary human lymphoid organs, its product, polysialic acid (polySia), has been largely overlooked by immunologists. In contrast, polySia expression and function in the nervous system has been well characterized. In this context, polySia modulates cellular adhesion, migration, cytokine response, and contact-dependent differentiation. Provocatively, these same processes are vital components of immune development and function. We previously established that mouse multipotent hematopoietic progenitors use ST8Sia IV to express polySia on their cell surfaces. Here, we demonstrate that, relative to wild-type controls, ST8Sia IV(-/-) mice have a 30% reduction in total thymocytes and a concomitant deficiency in the earliest thymocyte precursors. T-cell progenitors originate in the bone marrow and are mobilized to the blood at regular intervals by unknown signals. We performed in vivo reconstitution experiments in which ST8Sia IV(-/-) progenitors competed with wild-type cells to repopulate depleted or deficient immune subsets. Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. This phenotype probably reflects a decreased capacity of the ST8Sia IV(-/-) progenitors to escape from the bone marrow niche. Collectively, these results provide evidence that polySia is involved in hematopoietic development.

Spinal arthrodesis via lumbar interbody fusion without direct decompression as a treatment for recurrent radicular pain due to epidural fibrosis: patient series.

BACKGROUND: Lumbar radiculopathy is the most common indication for lumbar discectomy, but residual postoperative radicular symptoms are common. Postoperative lumbar radiculopathy secondary to scar formation is notoriously difficult to manage, with the mainstay of treatment focused on nonoperative techniques. Surgical intervention for epidural fibrosis has shown unacceptably high complication rates and poor success rates. OBSERVATIONS: Three patients underwent spinal arthrodesis without direct decompression for recurrent radiculopathy due to epidural fibrosis. Each patient previously underwent lumbar discectomy but subsequently developed recurrent radiculopathy. Imaging revealed no recurrent disc herniation, although it demonstrated extensive epidural fibrosis and scar in the region of the nerve root at the previous surgical site. Dynamic radiographs showed no instability. Two patients underwent lateral lumbar interbody fusion, and one patient underwent anterior lumbosacral interbody fusion. Each patient experienced resolution of radicular symptoms by the 1-year follow-up. Average EQ visual analog scale scores improved from 65 preoperatively to 78 postoperatively. LESSONS: Spinal arthrodesis via lumbar interbody fusion, without direct decompression, may relieve pain in patients with recurrent radiculopathy due to epidural fibrosis, even in the absence of gross spinal instability.

Polysialic acid, a glycan with highly restricted expression, is found on human and murine leukocytes and modulates immune responses.

Polysialic acid (polySia) is a large glycan with restricted expression, typically found attached to the protein scaffold neural cell adhesion molecule (NCAM). PolySia is best known for its proposed role in modulating neuronal development. Its presence and potential functions outside the nervous systems are essentially unexplored. Herein we show the expression of polySia on hematopoietic progenitor cells, and demonstrate a role for this glycan in immune response using both acute inflammatory and tumor models. Specifically, we found that human NK cells modulate expression of NCAM and the degree of polymerization of its polySia glycans according to activation state. This contrasts with the mouse, where polySia and NCAM expression are restricted to multipotent hematopoietic progenitors and cells developing along a myeloid lineage. Sialyltransferase 8Sia IV(-/-) mice, which lacked polySia expression in the immune compartment, demonstrated an increased contact hypersensitivity response and decreased control of tumor growth as compared with wild-type animals. This is the first demonstration of polySia expression and regulation on myeloid cells, and the results in animal models suggest a role for polySia in immune regulation.

A socioeconomic survey of spinal cord stimulation (SCS) surgery.

OBJECTIVE: We evaluated trends in inpatient spinal cord stimulation (SCS) for the 14-year period from 1993 to 2006. MATERIALS AND METHODS: We utilized the Nationwide Inpatient Sample data base from the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. RESULTS: A total of 57,486 patients underwent inpatient placement of SCS systems from 1993 to 2006. Length of stay steadily decreased from 4.0 days in 1993 to 2.1 days in 2006. Average cost increased from $15,342 in 1993 to nearly $58,088 in 2006. The National Bill for SCS surgery in 2006 alone totaled nearly $215MM. Medicare accounted for 35% of payers, while private insurance accounted for 41% of claims. CONCLUSIONS: Given the expense of these systems, it is important to assess not only the efficacy of novel neuromodulatory interventions, but also their cost. Future studies should be designed with these important outcome measures in mind.

Smartphone Use and Interest in a Spine Surgery Recovery Mobile Application Among Patients in a US Academic Neurosurgery Practice.

BACKGROUND: Mobile applications (apps) are serving an increasingly important role in healthcare for patients and providers alike. In addition to streamlining active communication of patient-reported outcomes regarding quality of life, pain, and opioid consumption, smartphones equipped with activity tracking afford the opportunity to passively and objectively measure mobility, a key metric of recovery in spine surgery. However, app development is a resource-intensive process. OBJECTIVE: To survey adult neurosurgery patients regarding access to and interest in this platform. METHODS: In June and July 2017, a paper-based anonymous survey was distributed to patients in the waiting room of the adult neurosurgery clinic of a large US academic medical center. Patients' smartphone use and interest in using a mobile app following spine surgery were the primary and secondary outcomes, respectively. RESULTS: Of 146 included responses, 102 patients (70%) regularly used a smartphone, and this number increased to 77% among patients with a history of spine surgery (n = 66, 45% of respondents). Seventy-one percent of patients with previous spine surgery expressed an interest in using a postoperative monitoring and communication app, compared to 81% of patients without prior spine operations (n = 80, 55%). CONCLUSION: Among neurosurgery patients, there is a high level of access to and interest in smartphone apps to aid postoperative recovery. These results are useful for other neurosurgeons considering mobile app development for this purpose.

Correlation between the Oswestry Disability Index and the 4-item short forms for physical function and pain interference from PROMIS.

OBJECTIVE: The Oswestry Disability Index (ODI) is one of the most commonly used patient-reported outcome instruments, but completion of this 10-question survey can be cumbersome. Tools from the Patient-Reported Outcomes Measurement Information System (PROMIS) are an alternative, and potentially more efficient, means of assessing physical, mental, and social outcomes in spine surgery. Authors of this retrospective study assessed whether scores on the 4-item surveys of function and pain from the PROMIS initiative correlate with those on the ODI in lumbar spine surgery. METHODS: Patients evaluated in the adult neurosurgery spine clinic at a single institution completed the ODI, PROMIS Short Form v2.0 Physical Function 4a (PROMIS PF), and PROMIS Short Form v1.0 Pain Interference 4a (PROMIS PI) at various time points in their care. Score data were retrospectively analyzed using linear regressions with calculation of the Pearson correlation coefficient. RESULTS: Three hundred forty-three sets of surveys (ODI, PROMIS PF, and PROMIS PI) were obtained from patients across initial visits (n = 147), 3-month follow-ups (n = 107), 12-month follow-ups (n = 52), and 24-month follow-ups (n = 37). ODI scores strongly correlated with PROMIS PF t-scores at baseline (r = -0.72, p < 0.0001), 3 months (r = -0.79, p < 0.0001), 12 months (r = -0.85, p < 0.0001), and 24 months (r = -0.89, p < 0.0001). ODI scores also correlated strongly with PROMIS PI t-scores at baseline (r = 0.71, p < 0.0001), at 3 months (r = 0.82, p < 0.0001), at 12 months (r = 0.86, p < 0.0001), and at 24 months (r = 0.88, p < 0.0001). Changes in ODI scores moderately correlated with changes in PROMIS PF t-scores (r = -0.68, p = 0.0003) and changes in PROMIS PI t-scores (r = 0.57, p = 0.0047) at 3 months postoperatively. CONCLUSIONS: A strong correlation was found between the ODI and the 4-item PROMIS PF/PI at isolated time points for patients undergoing lumbar spine surgery. Large cohort studies are needed to determine longitudinal accuracy and precision and to assess possible benefits of time savings and improved rates of survey completion.

The stroke navigator: meaningful use of the electronic health record to efficiently report inpatient stroke care quality.

To facilitate high-quality inpatient care for stroke patients, we built a system within our electronic health record (EHR) to identify stroke patients while they are in the hospital; capture necessary data in the EHR to minimize the burden of manual abstraction for stroke performance measures, decreasing daily time requirement from 2 hours to 15 minutes; generate reports using an automated process; and electronically transmit data to third parties. Provider champions and support from the EHR development team ensured that we balanced the needs of the hospital with those of frontline providers. This work summarizes the development and implementation of our stroke quality system.

Placement of a subdural evacuating port system for management of iatrogenic hyperacute subdural hemorrhage following intracranial monitor placement.

A 22-year-old man was admitted with a severe traumatic brain injury developed a hyperacute subdural hematoma (SDH) following attempted brain tissue oxygen monitor placement. This patient was successfully treated by placement of a subdural evacuation portal system (SEPS). The patient presented to a Level I trauma center after a severe bike versus auto accident. On admission, he was found to have a Glasgow Coma Scale (GCS) score of 3. The patient had small areas of intraparechymal hemorrhage as well as suspicion for diffuse axonal injury in the midbrain. Based on the patient's GCS score, neurological monitoring was indicated as a part of his intensive care unit treatment, however a SDH occurred during an attempted placement of a brain tissue oxygen monitor. This iatrogenic hyperacute SDH after burr hole monitoring device placement was treated with a SEPS drain. The SEPS drain has been shown to provide complete and/or temporary decompression of liquefied SDH. To our knowledge, this is the first report of using the SEPS to treat iatrogenic SDH associated with an intracranial monitoring device. This technique should be added to the armament of treatment options for a neurosurgeon to treat or temporize a hyperacute SDH with increased intracranial pressure in specific patients.

Multi-institutional validation of a preoperative scoring system which predicts survival for patients with glioblastoma.

Glioblastoma is the most common and aggressive type of primary brain tumor in adults. Average survival is approximately 1 year, but individual survival is heterogeneous. Using a single institutional experience, we have previously identified preoperative factors associated with survival and devised a prognostic scoring system based on these factors. The aims of the present study are to validate these preoperative factors and verify the efficacy of this scoring system using a multi-institutional cohort. Of the 334 patients in this study from three different institutions, the preoperative factors found to be negatively associated with survival in a Cox analysis were age >60 years (p<0.0001), Karnofsky Performance Scale score ≤80 (p=0.03), motor deficit (p=0.02), language deficit (p=0.04), and periventricular tumor location (p=0.04). Patients possessing 0-1, 2, 3, and 4-5 of these variables were assigned a preoperative grade of 1, 2, 3, and 4, respectively. Patients with a preoperative grade of 1, 2, 3, and 4 had a median survival of 17.9, 12.3, 10, and 7.5 months, respectively. Survival of each of these grades was statistically significant (p<0.05) in log-rank analysis. This grading system, based only on preoperative variables, may provide patients and physicians with prognostic information that may guide medical and surgical therapy before any intervention is pursued.

Trends in the use of bone morphogenetic protein as a substitute to autologous iliac crest bone grafting for spinal fusion procedures in the United States.

STUDY DESIGN: Analysis of Nationwide Inpatient Sample (NIS) database for data related to spinal fusion procedures. OBJECTIVE: To identify trends in the use of bone morphogenetic protein (BMP) versus iliac crest bone grafts in various spinal fusion procedures performed in the United States, explore stratification by patient demographics, and analyze the impact on treatment cost. SUMMARY OF BACKGROUND DATA: BMP has been shown to achieve better clinical outcomes in anterior lumbar interbody fusions procedures, which led to its Food and Drug Administration approval for this indication in 2002. Since then, significant off-label use has occurred, without a full description of the results. METHODS: We searched the NIS for data relating to BMP administration or iliac crest bone grafting in a variety of spinal fusion procedures performed from 1993 to 2006, based on International Classification of Diseases, Ninth Revision classification. The NIS is the largest all-payer inpatient care database, with demographic, outcome, and cost data from approximately eight million annual patient discharges throughout the United States. Demographics among patients treated with BMP versus iliac crest bone graft were compared to reduce the likelihood of bias in the analysis. RESULTS: BMP became applied more frequently in each type of spinal fusion procedure examined over our study period, with the exception of anterior lumbar interbody fusions. Patients receiving iliac crest bone grafts versus BMP exhibited very similar demographic characteristics, including age, socioeconomic status, and type of health care setting. Although BMP typically increased the cost of the procedure itself, it improved outcomes and shorter hospital stays often provided a net benefit. CONCLUSION: BMP is increasingly being used in spinal fusion procedures, including ones for which it is not officially approved, because of the surgical and postsurgical benefits it provides. Given the morbidity that this may entail, monitoring outcomes trends will help to inform guidelines for BMP use and ensure that its benefits continue to outweigh its costs.

Trends in median, ulnar, radial, and brachioplexus nerve injuries in the United States.

UNLABELLED: significant constraints on an individual's quality of life. OBJECTIVE: To promote efforts to reduce exposure to injury risk factors and to utilize effective therapies when damage does occur, it is important to understand historical trends in both the demographics of peripheral nerve injury (PNI) patients and their treatment. We sought to examine some of these trends. METHODS: We searched the Nationwide Inpatient Sample for discharges classified with International Classification of Diseases, Ninth Revision diagnosis codes of median, ulnar, radial, or brachioplexus nerve injury between 1993 and 2006. We analyzed these data to obtain trend information for the number of discharges, hospital charges, treatment course, patient demographics, and other measures. RESULTS: Although aggregate discharges involving these injuries decreased slightly between 1993 and 2006, mean nominal hospital charges for their treatment increased significantly, in particular, for brachial plexus injuries. In 2006 30 to 40% of median, ulnar, and radial nerve injuries required acute repair by direct nerve suture. PNI patients in 2006 were more likely to be male, between the ages of 18 and 44 years, and from regions where the median income level is greater than $36 000. Approximately 75% of PNIs were treated in academic hospitals and 95% in metropolitan areas. CONCLUSION: PNIs are complex injuries that primarily affect males in key years of adulthood, frequently requiring high-cost acute surgical repair. Although there has been a slight decline in their incidence in the past decade, treatment cost has increased.

High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells.

CD22 (Siglec-2) is a key regulator of B cell signaling whose function is modulated by interaction with extracellular glycan ligands mediated through its N-terminal Ig domain. Its preferred ligand is the sequence Sia alpha2-6Gal that is abundantly expressed on N-linked glycans of B cell glycoproteins, and by binding to CD22 in cis causes CD22 to appear "masked" from binding to synthetic sialoside probes. Yet, despite the presence of cis ligands, CD22 redistributes to sites of cell contact by binding to trans ligands on neighboring cells. In this study, we demonstrate the dynamic equilibrium that exists between CD22 and its cis and trans ligands, using a high-affinity multivalent sialoside probe that competes with cis ligands and binds to CD22 on native human and murine B cells. Consistent with the constitutive endocytosis reported for CD22, the probes are internalized once bound, demonstrating that CD22 is an endocytic receptor that can carry ligand-decorated "cargo" to intracellular compartments. Conjugation of the sialoside probes to the toxin saporin resulted in toxin uptake and toxin-mediated killing of B lymphoma cell lines, suggesting an alternative approach for targeting CD22 for treatment of B cell lymphomas.