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OBJECTIVE Differences in insurer and payer status have been shown to increase patient hospital length of stay (LOS) by delaying the approval of transfer to a rehabilitation facility. The aim of the current study is to determine the impact of the type of insurance provider on postoperative hospital LOS after spine surgery. METHODS In our single-institution retrospective study, all patients undergoing elective spine surgery between August 2018 and August 2019 as part of an enhanced recovery after surgery (ERAS) protocol were enrolled in a prospectively collected registry. Insurance payer type was analyzed to determine its effect on total patient LOS after surgery. RESULTS A total of 106 patients were included in the study. Insurance payers studied were Medicare, private insurers (preferred provider organization and health maintenance organization), and the Veterans Affairs payer TriWest. Patients in all groups had comparable demographic characteristics and procedural variables. There was a statistically significant difference in days stayed beyond medical clearance among the 3 insurance provider groups (P < 0.001); TriWest patients stayed an average of 3.2 days beyond clearance, compared with private insurance (1.2 days) and Medicare (0.3 days). Individual subanalysis of the ERAS complex pathway population mirrored these findings. CONCLUSIONS Hospitalization beyond medical clearance after spine surgery follows a predictable pattern regardless of ERAS pathway complexity, with Medicare having a shorter delay in approving patient progression than private insurance, which has less of a delay than Triwest.

Tobacco use and narcotic medication have been associated with worse functional outcomes after surgery. Our goal was to investigate potential associations between smoking and preoperative opioid consumption in a geriatric population undergoing spine surgery, and their impact on postoperative outcomes. The records of 536 consecutive patients aged more than 65 years who underwent elective spinal surgery between November 2014 and August 2017 at a single institution were reviewed. Primary outcomes included rates of preoperative opioid consumption and postoperative hospital length of stay and complications. Males were more likely to be smokers than females (p 0.001), whereas females were more likely to take opioid analgesics preoperatively (p = 0.022). Women with a history of smoking were more likely to have increased preoperative opioid consumption compared to those with no history of smoking (63.64% vs. 42.04%; p 0.001). Such a relationship was not found in men. Subgroups analysis of female patients with a history of tobacco use comparing current and former smoker status showed that both groups exhibited increased preoperative opioid consumption compared to patients who never smoked (88.89% vs 42.04%; p 0.001 for current users; 59.42% vs 42.04% for former users; p = 0.008). There was also a dose-depended relationship between smoking and increased preoperative opioid consumption. Geriatric female spine patients with a history of smoking have a higher incidence of preoperative opioid consumption. Opioid intake appears to increase with the number of pack-years, both in patients with a history of smoking and in those who currently smoke.

OBJECTIVEThe aim of this study was to determine if the use of tranexamic acid (TXA) in long-segment spinal fusion surgery can help reduce perioperative blood loss, transfusion requirements, and morbidity.METHODSIn this retrospective single-center study, the authors included 119 consecutive patients who underwent thoracolumbar fusion spanning at least 4 spinal levels from October 2016 to February 2019. Blood loss, transfusion requirements, perioperative morbidity, and adverse thrombotic events were compared between a cohort receiving intravenous TXA and a control group that did not.RESULTSThere was no significant difference in any measure of intraoperative blood loss (1514.3 vs 1209.1 mL, p = 0.29) or transfusion requirement volume between the TXA and control groups despite a higher number of pelvic fusion procedures in the TXA group (85.9% vs 62.5%, p = 0.003). Postoperative transfusion volume was significantly lower in TXA patients (954 vs 572 mL, p = 0.01). There was no difference in the incidence of thrombotic complications between the groups.CONCLUSIONSTXA appears to provide a protective effect against blood loss in long-segment spine fusion surgery specifically when pelvic dissection and fixation is performed. TXA also seems to decrease postoperative transfusion requirements without increasing the risk of adverse thrombotic events.

Simple Summary Modifications in the repertoire of N-glycans at the cell surface are associated with neurological complications. However, knowledge of specific N-glycans as to their impact on neuronal excitability is lacking. Our proposed studies will elucidate the roles of distinct N-glycan structures in modulating potassium channel function in highly repetitive firing neurons. This study is instrumental in understanding the development and progression of neurological diseases, thus, opening the door for potential therapeutic options. Abstract Neurological difficulties commonly accompany individuals suffering from congenital disorders of glycosylation, resulting from defects in the N-glycosylation pathway. Vacant N-glycosylation sites (N220 and N229) of Kv3, voltage-gated K+ channels of high-firing neurons, deeply perturb channel activity in neuroblastoma (NB) cells. Here we examined neuron development, localization, and activity of Kv3 channels in wildtype AB zebrafish and CRISPR/Cas9 engineered NB cells, due to perturbations in N-glycosylation processing of Kv3.1b. We showed that caudal primary (CaP) motor neurons of zebrafish spinal cord transiently expressing fully glycosylated (WT) Kv3.1b have stereotypical morphology, while CaP neurons expressing partially glycosylated (N220Q) Kv3.1b showed severe maldevelopment with incomplete axonal branching and extension around the ventral musculature. Consequently, larvae expressing N220Q in CaP neurons had impaired swimming locomotor activity. We showed that replacement of complex N-glycans with oligomannose attached to Kv3.1b and at cell surface lessened Kv3.1b dispersal to outgrowths by altering the number, size, and density of Kv3.1b-containing particles in membranes of rat neuroblastoma cells. Opening and closing rates were slowed in Kv3 channels containing Kv3.1b with oligomannose, instead of complex N-glycans, which suggested a reduction in the intrinsic dynamics of the Kv3.1b α-subunit. Thus, N-glycosylation processing of Kv3.1b regulates neuronal development and excitability, thereby controlling motor activity.

Objective We aimed to study the relationship between psychiatric Disorders (PD), preoperative pain, and opioid medication intake, as well as the quality of life patient-reported outcome measures using the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) questionnaire, during the 30-day interval preceding surgery, in a consecutive series of patients who were scheduled to undergo surgical spine procedures. We hypothesized that PD could affect preoperative narcotic use and pain interference in a fashion that was not linearly associated with preoperative pain in spine surgery candidates. Methods The records of consecutive adult patients who underwent elective spinal surgery between October 2016 and August 2017 at a single institution were reviewed. We included patients who underwent preoperative pain assessment within 30 days prior to their planned surgery using the PROMIS-29 questionnaire. Patients with PD were compared to controls. Results A total of 117 patients matched our criteria. The average rating of pain intensity was notably higher in the PD group as compared to controls (p=0.004). The PD group had more patients complaining of high pain levels (>6) as compared to the control group (p=0.026). Controls with high pain levels had a greater incidence of preoperative narcotic use as compared to the low-pain cohort (p=0.029). However, there was no difference in the actual dose of daily narcotic medication taken between the PD and control groups (P=0.099) or between the low- and high pain score groups in the control (p=0.291) and PD (p=0.441) groups, respectively. Patients with PD and higher pain ratings seemed to have a higher incidence of anxiety (p=0.005) and depression (p

Objective We aimed to assess the impact of surgical intervention on outcome in patients diagnosed with demyelinating disorders and cervical degenerative disease warranting surgical intervention. Methods The records of patients with a diagnosis of a demyelinating disorder of the central nervous system who underwent cervical spine surgery at a single institution from 2016 to 2020 were reviewed. Demyelinating disease included multiple sclerosis (MS), neuromyelitis optica, and transverse myelitis (TM). The dates of initial spine symptom onset, recognition of spinal pathology by the primary provider, referral to spine surgery, and spine surgery procedures were collected. Hospital length of stay (LOS) and postoperative outcomes and complications were recorded. Results A total of 19 patients with a diagnosis of demyelinating disorders underwent cervical spine surgery at our institution. Seventeen patients had MS. The average time interval between a documented diagnosis of myelopathy or radiculopathy and referral to the Spine clinic was 67.95 months (M=40, SD=64.87). Twelve patients had imaging studies depicting degenerative spine disease that would warrant surgical intervention at the time of examination by their primary physician. The average delay for referral to the Spine clinic for these patients was 16.5 months (M=5; SD=25.36). More than 89% of patients experienced significant neurologic improvement postoperatively. Conclusions There is a delay in the recognition of cervical spine disease amenable to a surgical resolution in patients with demyelinating disorders. Surgical treatment can lead to significant clinical improvement in this patient population even if delayed, and likely carries similar risk to that of the general population.

Purpose To determine the prevalence and morphologic features of reticular pseudodrusen (RPD) and their association with participant demographics and age-related macular degeneration (AMD) status in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) sample, an ancillary study of the Women’s Health Initiative Observational Study. Design Cross-sectional, multicenter, natural history study. Participants Nine hundred and twenty-seven eyes from 466 postmenopausal women 69 to 101 years of age. Methods Multimodal imaging, including spectral-domain (SD) OCT and infrared reflectance (IR), were used to identify RPD characteristics, including location (within or outside the 6-mm diameter circle centered at the macula), presence of peripapillary RPD, pattern of RPD, and RPD area. Age-related macular degeneration features from SD OCT, IR, and color photographs also were assessed and AMD severity was categorized. Main Outcome Measures Reticular pseudodrusen prevalence using SD OCT and IR imaging and AMD status. Results Reticular pseudodrusen were present in 130 eyes (14% of eyes, 16% of participants), with increasing prevalence with age: 7% in those younger than 78 years, 14% in those 78 to 83 years of age, and 30% in those older than 83 years. Using clinical classification of AMD with color photography, RPD were seen in 2.4% of eyes with no AMD or aging changes, 11.5% in early AMD, 25.1% in intermediate AMD, and 51.1% in late AMD. Mean RPD area was 17.4 mm2 (standard deviation, 14.7 mm2). Ribbon morphologic RPD (53%) was more common than dot morphologic RPD (36%). Reticular pseudodrusen mostly were located both within and outside the 6-mm circle with primarily superior retinal distribution. Reticular pseudodrusen were visualized with corresponding color fundus photography in only 38 eyes (4% of total eyes). Participants with and without RPD had a visual acuity±standard error of 77.9 ± 1.4 letters and 81.3 ± 0.4 letters, respectively (P = 0.02). Conclusions The prevalence of RPD in CAREDS2 increased with age and was associated with AMD severity. Reticular pseudodrusen were detected in eyes without other features of AMD and could represent an earlier disease state. Multimodal imaging with SD OCT and IR has significantly greater sensitivity for visualizing RPD than color fundus photography.

BACKGROUND Delirium is a common postoperative complication in geriatric patients, especially in those with underlying risk factors. Multicomponent nonpharmacologic interventions are effective in preventing delirium, however, implementation of these measures is variable in perioperative care. The aim of our study was to assess the impact of our Perioperative Optimization of Senior Health Program (UTSW POSH) on postoperative delirium in patients undergoing elective spine surgery. STUDY DESIGN The UTSW POSH program is an interdisciplinary perioperative initiative involving geriatrics, surgery, and anesthesiology to improve care for high-risk geriatric patients undergoing elective spine surgery. Preoperatively, enrolled patients (n = 147) were referred for a geriatric assessment and optimization for surgery. Postoperatively, patients were co-managed by the primary surgical team and the geriatrics consult service. UTSW POSH patients were retrospectively compared to a matched historical control group (n = 177) treated with usual care. Main outcomes included postoperative delirium and provider recognition of delirium. RESULTS UTSW POSH patients were significantly older (75.5 vs 71.5 years; P

Background Lung disease is a leading cause of morbidity and mortality. A breach in the lung alveolar-epithelial barrier and impairment in lung function are hallmarks of acute and chronic pulmonary illness. This review is part two of our previous work. In part 1, we demonstrated that CdM is as effective as MSCs in modulating inflammation. Herein, we investigated the effects of mesenchymal stromal cell (MSC)-conditioned media (CdM) on (i) lung architecture/function in animal models mimicking human lung disease, and (ii) performed a head-to-head comparison of CdM to MSCs. Methods Adhering to the animal Systematic Review Centre for Laboratory animal Experimentation protocol, we conducted a search of English articles in five medical databases. Two independent investigators collected information regarding lung: alveolarization, vasculogenesis, permeability, histologic injury, compliance, and measures of right ventricular hypertrophy and right pulmonary pressure. Meta-analysis was performed to generate random effect size using standardized mean difference with 95% confidence interval. Results A total of 29 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. CdM improved all measures of lung structure and function. Moreover, no statistical difference was observed in any of the lung measures between MSCs and CdM. Conclusions In this meta-analysis of animal models recapitulating human lung disease, CdM improved lung structure and function and had an effect size comparable to MSCs.

BACKGROUND Perioperative pain can negatively impact patient recovery after spine surgery and be a contributing factor to increased hospital length of stay and cost. Most data currently available is extrapolated from adolescent idiopathic cases and may not apply to adult and geriatric populations with thoracolumbar spine degeneration. PURPOSE Study the impact of epidural analgesia on pain control and outcomes after adult degenerative scoliosis surgery in a large single-institution series of adult patients undergoing thoraco-lumbar-pelvic fusion. STUDY DESIGN/SETTING Retrospective single-center review of prospectively collected data. PATIENT SAMPLE Patients undergoing thoracolumbar fusion with pelvic fixation. OUTCOME MEASURES Self-reported measures: Visual analog scale for pain. Physiologic Measures: Oral pain control requirements converted into daily morphine equivalents. Functional Measures: Ambulation perimeter after surgery, urinary retention and constipation rates. METHODS We retrospectively reviewed patient data for the years 2016 and 2017 before the use of patient controlled epidural analgesia (PCEA), and then 2018 and 2019 after its implementation, for all thoracolumbar degenerative procedures, and compared their postoperative outcomes measures. RESULTS There were 46 patients in the PCEA group and 37 patients in the intravenous PCA (IVPCA) groups. All patients underwent long segment posterolateral thoracolumbar spinal fusion with pelvic fixation. Patients in the PCEA group had lower pain scores and ambulated greater distances compared with those in the IVPCA group. PCEA patients also had lower urinary retention and constipation rates, but no increased intraoperative or postoperative complications related to catheter placement. CONCLUSIONS PCEA can provide optimal pain control after adult degenerative scoliosis spine surgery, and may promote greater early ambulation, while decreasing postoperative constipation and urinary retention rates.

Chordomas are rare and difficult-to-treat tumors arising from the embryonic notochord. While surgery is the mainstay of treatment, and despite new techniques aimed at maximizing total tumoral resection, recurrence remains high and the probability of disease-free survival low. New breakthroughs in genetics, targeted molecular therapy, and heavy-particle beam therapy offer some promise as adjuvant treatments in addition to surgical resection. A multidisciplinary approach encompassing genetics, immunotherapy, radiation therapy, and surgery, at a facility experienced in the management of this complex disease, offers the best chance of survival and quality of life to patients while limiting the intrinsic morbidity of these treatments.

The analysis of perioperative electronic patient portal (EPP) communication may provide risk stratification and insight for complication prevention in patients with affective disorders (ADs). We aimed to understand how patterns of EPP communication in patients with AD relate to preoperative narcotic use, surgical outcomes, and readmission rates.The records of adult patients who underwent elective spinal surgery between January 2010 and August 2017 at a single institution were retrospectively reviewed for analysis. Primary outcomes included preoperative narcotic use, the number of perioperative EPP messages sent, rates of perioperative complications, hospital length of stay, emergency department (ED) visits within 6 weeks, and readmissions within 30 days after surgery.A total of 1199 patients were included in the analysis. Patients with an AD were more likely to take narcotics before surgery (51.69% vs. 41%, P0.001) and to have active EPP accounts (75.36% vs. 69.75%, P = 0.014) compared with controls. They were also more likely to send postoperative messages (38.89% vs. 32.75%, P = 0.030) and tended to send more messages (0.67 vs. 0.48, P = 0.034). The AD group had higher rates of postoperative complications (8.21% vs. 3.98%, P = 0.001), ED visits (4.99% vs. 2.43%, P = 0.009), and readmissions postoperatively (2.49% vs. 1.38%, P = 0.049).AD patients have specific patterns of perioperative EPP communication. They are at a higher risk of postoperative complications. Addressing these concerns early may prevent more serious morbidity and avoid unnecessary ED visits and readmissions, thus reducing costs and improving patient care.

Neuroblastoma (NB) development and progression are accompanied by changes in N-glycans attached to proteins. Here, we investigated the role of N-acetylglucosaminyltransferase-II (GnTII, MGAT2) protein substrates in neuroblastoma (NB) cells. MGAT2 was silenced in human BE(2)-C NB (HuNB) cells to generate a novel cell line, HuNB(-MGAT2), lacking complex type N-glycans, as in rat B35 NB cells. Changes in N-glycan types were confirmed by lectin binding assays in both cell lines, and the rescued cell line, HuNB(-/+MGAT2). Western blotting of cells heterologously expressing a voltage-gated K+ channel (Kv3.1b) showed that some hybrid N-glycans of Kv3.1b could be processed to complex type in HuNB(-/+MGAT2) cells. In comparing HuNB and HuNB(-MGAT2) cells, decreased complex N-glycans reduced anchorage-independent cell growth, cell proliferation, and cell invasiveness, while they enhanced cell-cell interactions. Cell proliferation, invasiveness and adhesion of the HuNB(-/+MGAT2) cells were more like the HuNB than HuNB(-MGAT2). Western blotting revealed lower protein levels of MMP-2, EGFR and Gab2 in glycosylation mutant cells relative to parental cells. Gelatin zymography demonstrated that decreased MMP-2 protein activity was related to lowered MMP-2 protein levels. Thus, our results support that decreased complex type N-glycans suppress cell proliferation and cell invasiveness in both NB cell lines via remodeling ECM.

Objective Spinal involvement in neurocysticercosis is rare and can lead to debilitating injury if not diagnosed and treated early. We aim to provide the reader with a thorough analysis of the best available evidence regarding patient characteristics, optimal treatment modality, and outcomes in cases of spinal neurocysticercosis. Methods A systematic review of the literature using PubMed, Google Scholar, and Web of Science electronic databases was made according to the PRISMA guidelines. An illustrative case of intramedullary–cervical spinal disease is also presented for illustrative purposes. Results A total of 46 reports of 103 patients fitting the screening criteria were identified. Isolated spinal involvement was seen in 46.15% of patients. Most infections (76.92%) had an intradural extramedullary localization, with 43.27% of cases involving >1 spinal cord level. The most common presenting symptoms were motor deficits (77.88%), pain syndromes (64.42%), and sensory deficits (53.85%). Combined surgical resection and pharmacologic therapy was the most frequently used treatment modality (49.04%) and had the highest proportion of patients reporting symptomatic improvement at follow-up (78.43%). Combination therapy had a significantly higher rate of neurologic recovery compared with surgery alone (P = 0.004) or medical treatment (P = 0.035). Conclusions Spinal involvement in neurocysticercosis should be considered in patients from or who traveled to endemic areas presenting with ring-enhancing lesions. Combined treatment with surgery followed by cysticidal and steroid medication seems to be superior to surgery or medical treatment in isolation and seems to provide the highest chances of recovery.

Tumor development can be promoted/suppressed by certain N-glycans attached to proteins at the cell surface. Here we examined aberrant neuronal properties in 2D and 3D rat neuroblastoma (NB) cell cultures with different N-glycan populations. Lectin binding studies revealed that the engineered N-glycosylation mutant cell line, NB_1(-Mgat1), expressed solely oligomannose N-glycans, and verified that the parental cell line, NB_1, and a previous engineered N-glycosylation mutant, NB_1(-Mgat2), expressed significant levels of higher order N-glycans, complex and hybrid N-glycans, respectively. NB_1 grew faster than mutant cell lines in monolayer and spheroid cell cultures. A 2-fold difference in growth between NB_1 and mutants occurred much sooner in 2D cultures relative to that observed in 3D cultures. Neurites and spheroid cell sizes were reduced in mutant NB cells of 2D and 3D cultures, respectively. Cell invasiveness was highest in 2D cultures of NB_1 cells compared to that of NB_1(-Mgat1). In contrast, NB_1 spheroid cells were much less invasive relative to NB_1(-Mgat1) spheroid cells while they were more invasive than NB_1(-Mgat2). Gelatinase activities supported the ranking of cell invasiveness in various cell lines. Both palladin and HK2 were more abundant in 3D than 2D cultures. Levels of palladin, vimentin and EGFR were modified in a different manner under 2D and 3D cultures. Thus, our results support variations in the N-glycosylation pathway and in cell culturing to more resemble in vivo tumor environments can impact the aberrant cellular properties, particularly cell invasiveness, of NB.

BACKGROUND CONTEXT Enhanced Recovery After Surgery (ERAS) programs have been consistently shown to reduce surgical complications, decrease hospital costs and improve patient-reported outcomes across multiple surgical specialties. This benefit has been shown to be applicable to surgical spinal procedures, and to reduce hospital length of stay and decrease overall surgery costs. However, most publications to date offer heterogeneous data with a mix of patients undergoing minor procedures such as minimally invasive discectomies, and others undergoing multiple level thoracic or lumbar fusions. The aim of our analysis was to assess the impact of ERAS pathways implementation in an older population undergoing open thoracolumbar fusion for degenerative scoliosis. PURPOSE Determine the impact of Enhanced Recovery After Surgery (ERAS) pathways implementation on postoperative outcome, opioid consumption, and unplanned readmission rates in adult patients undergoing open thoraco-lumbar-pelvic fusion for degenerative scoliosis. STUDY DESIGN/SETTING This study was conducted at a single academic spine center. All patients undergoing spine surgery had their data prospectively collected within our spine registry. Patient data was retrospectively reviewed for the years 2016 and 2017 prior to the implementation of our ERAS protocol, and then 2018 and 2019 after its implementation for all thoracolumbar degenerative procedures that were performed during that timeframe. PATIENT SAMPLE All subjects included in the analysis underwent long segment thoraco-lumbar-pelvic fusion for adult degenerative scoliosis. OUTCOME MEASURES Primary outcomes consisted of postoperative supplementary opioid consumption in Morphine Equivalent Dose (MED), postoperative complications, and readmission rates within the postoperative 30-day window. METHODS In this retrospective single-center study, we included 124 consecutive patients who underwent open thoraco-lumbar-pelvic fusion from October 2016 to February 2019 for degenerative scoliosis. Patient demographic information included age, weight and body mass index. The operative parameters comprised the number of segments fused, the Cobb angle of the deformity, operative time, anesthesia duration and intraoperative blood loss volume. Primary patient outcomes consisted of supplemental total opioid intake in addition to standard intravenous or epidural patient-controlled analgesia for the duration of postoperative hospital stay in Morphine Equivalent Dosage (MED), postoperative complications and readmission rates within the postoperative 30-day window. RESULTS There were 67 patients in the ERAS group, and 57 patients served as pre-ERAS controls. Average patient age was 69 years. The groups had comparable demographic and intraoperative variables. ERAS patients had a significantly lower rate of postoperative supplemental opioid consumption (248.05 vs 314.05 MED, p=0.04), a lower rate of urinary retention requiring catheterization (5.97% vs 19.3%, p=0.024) and of severe constipation (1.49% vs 31.57%, p CONCLUSIONS A comprehensive multidisciplinary approach to complex spine surgery can reduce opioid intake, postoperative urinary retention and severe constipation, and unplanned 30-day readmissions in the elderly adult population. Our findings show that a comprehensive ERAS program can potentially decrease complications and improve outcomes in the adult and elderly population who suffer from scoliosis. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT The UT Southwestern Perioperative Optimization of Senior Health (UTSW POSH) program is an interdisciplinary effort involving surgery, geriatrics, and anesthesia to provide specialized care to reduce morbidity in high-risk older adults undergoing elective surgery. One goal of the UTSW POSH program is to prevent postoperative delirium, an often underrecognized source of adverse outcomes that affects up to 50% of older adults undergoing surgery. PURPOSE The purpose of this study is to assess changes in the incidence of delirium before and after the implementation of the UTSW POSH program in high-risk older adults undergoing complex spinal surgery. STUDY DESIGN/SETTING Retrospective cohort study at a tertiary academic center. PATIENT SAMPLE High risk older adults (≥65 with >3 comorbidities, >5 prescription medications, known or suspected cognitive impairment, or BMI >25; all patients ≥85 years old) undergoing elective inpatient spinal deformity surgery (≥4 levels of fusion) between January 2014 and March 2019 (N=106). OUTCOME MEASURES The primary outcome was the incidence of delirium. Baseline characteristics and length of stay were also compared between groups. METHODS The UTSW POSH program was implemented January 2017. Patients referred to UTSW POSH and treated for complex spine surgery (n=61) by a neurosurgeon or orthopedic surgeon were evaluated approximately 30 days prior to surgery by a geriatric specialist and co-managed by the primary surgical team and an inpatient geriatrics team postoperatively. The geriatrics team provided delirium education, recommendations to prevent delirium, and daily postoperative delirium assessments on the ward. A risk factor and procedure-matched historical control group was created (n=45; January 2014 through December 2016) using UTSW POSH referral criteria for comparison of outcomes. Postoperative delirium was assessed via a validated retrospective chart review method and cases were confirmed with an expert geriatrician (SAW). RESULTS The mean age at the time of surgery was 73.5 years (UTSW POSH:74.5 years vs control: 72.3 years; p=0.03). At baseline, there were no significant differences between both patient cohorts in rates of polypharmacy, use of high-risk medications, baseline Hb, number of vertebral segments fused, or ASA classification. The incidence of delirium was significantly lower in UTSW POSH patients compared to control (11.4% vs 28.9%, p=0.03). Length of stay was decreased in the UTSW POSH cohort (5.37 days vs 7.34 days; p=0.003). CONCLUSIONS This study suggests that interdisciplinary care for high-risk older adults undergoing complex spine surgery can markedly reduce the incidence of postoperative delirium and decrease hospital length of stay. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Objective Renal cell carcinoma (RCC) metastases to the intramedullary spinal cord carry a grim prognosis. The purpose of this review is to provide the reader with a comprehensive and systematic review of the current literature, and to present an illustrative case that would aid in the future management of similar scenarios. Methods A systematic review of the literature using the PubMed electronic database was made according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only human clinical reports of intramedullary RCC metastasis were included. We also present an illustrative case that was treated at our institution. Results We identified 23 reports with a total of 31 patients. Of the tumors, 47% were located at the cervical level. Brain metastases were present in 41% of cases. Limb weakness (72%), urinary incontinence (41%), dysesthesia (47%), and localized spinal pain (38%) were the most frequently reported symptoms. Surgical resection alone was used in 34% of cases, followed by a combination of surgery and radiotherapy (31%), and radiotherapy alone (25%). Spinal metastases were detected an average of 32.1 months after the diagnosis of RCC, and mean patient survival after that was 8 months (range, 0–65 months). Reported survival after radiotherapy appeared to be the longest (11.2 months) compared with surgery (9.1 months) and combination therapy (5 months). Conclusions Intramedullary spinal metastatic RCC is a rare entity with debilitating neurologic potential. Survival appears to be affected by the treatment method but is also likely influenced by the stage of discovery of the disease.

BACKGROUND CONTEXT ERAS pathways are evidence-based protocols designed to reduce the surgical stress response and facilitate return to function, which typically results in a significant decrease in length of stay. After implementation of such a program at our institution, length of stay only transiently decreased. PURPOSE This study looks to identify barriers to timely discharge, and to assess a causal relationship with clearance from insurance payors. STUDY DESIGN/SETTING This is a retrospective cohort study of 105 consecutive patients undergoing elective spinal surgery on an ERAS pathway at a tertiary academic center. PATIENT SAMPLE N/A OUTCOME MEASURES N/A METHODS Prior to admission, all patients were assigned to intermediate (n=31) or complex (n=74) ERAS pathways according to their scheduled operation. Demographic data and variables related to comorbidities, insurance payor, length of stay, intra-and postoperative complications, discharge destination, and the date of medical clearance to discharge home or to a rehabilitation facility were recorded. The days stayed beyond medical clearance was calculated as the difference between the date of medical clearance and the actual date of discharge. Each operation was categorized according to the involvement of spinal fusion and by the number of vertebral levels. After patients were classified by payor type, Private Insurance, Medicare, and Triwest, the contracted payor for the Veterans Administration, were compared. RESULTS In complex pathway patients, there was no significant difference between the demographics, complication rates, or operative parameters in any of the groups. When compared overall and individually, there was a significant difference in mean length of stay between all groups (Private vs Medicare vs Triwest, 6.5 vs 5.1 vs 15.5 days, p = 0.002) that was mirrored in the days stayed beyond medical clearance (1.4 vs 0.3 vs 10, p = 0.001). This delay can translate into additional costs ranging between $14,000 and $140,000 per patient. In the intermediate pathway, Medicare patients were significantly older than Private Insurance or Triwest patients (72.7 vs 54.1 vs 54.6 years, p = 0.001), and the incidence of comorbid cancer was greater in the Private Insurance and Triwest cohorts compared to Medicare (50% vs 38% vs 0%, p = 0.007), but the remaining demographics were not different. There was no difference in length of stay (4 vs 3.15 vs 4.1 days, Private vs Medicare vs Triwest, p = 0.747), but the days beyond medical clearance was significant (0.7 vs 0 vs 1.5, p = 0.031), and it mirrored the complex group. The levels involved and fusion in each cohort were not different. 49% of patients on the complex pathway were discharged to inpatient rehabilitation facilities compared to 16% on the intermediate pathway. CONCLUSIONS Insurance payors can influence length of stay by delaying discharge authorization after spine surgery. The days stayed beyond medical clearance followed a regular pattern regardless of the pathway, with Medicare having less of a delay than Private Insurance, which had less of a delay than Triwest. When involving discharge to inpatient rehabilitation, this delay can significantly affect the total length of stay. Hospital stay beyond what is medically required represents a delay in appropriate patient care and unnecessary expenses that can be draining on our healthcare system, and that represents an opportunity for improvement across multiple procedures and specialties. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT The UT Southwestern Perioperative Optimization of Senior Health (UTSW POSH) program is an interdisciplinary effort involving surgery, geriatrics, and anesthesia to provide specialized care to high-risk older adults undergoing elective surgery. One goal of the UTSW POSH program is to prevent postoperative delirium, an often under-recognized source of adverse outcomes that affects up to 50% of older adults undergoing surgery. PURPOSE The purpose of this study is to assess changes in the incidence and provider recognition of delirium before and after implementation of UTSW POSH. STUDY DESIGN/SETTING Retrospective cohort study at a tertiary academic center. PATIENT SAMPLE High risk older adults (≥65 with >3 comorbidities, >5 prescription medications, known or suspected cognitive impairment, or BMI >25; all patients ≥85 years old) undergoing elective inpatient spine surgery between January 2014 and March 2019 (N=324). OUTCOME MEASURES The primary outcome was the incidence of delirium. Secondary outcomes included recognition of delirium and length of stay (LOS). Baseline characteristics were also compared between groups. METHODS The UTSW POSH program was implemented in January 2017. Patients referred to UTSW POSH and treated surgically (n=147) were evaluated approximately 30 days prior to surgery by a geriatric specialist and co-managed by the primary surgical team and an inpatient geriatrics team postoperatively. The geriatrics team provided patient and family delirium education, recommendations to prevent delirium, and daily postoperative delirium assessments. A risk factor- and procedure-matched historical control group was created (n=177; January 2014 through December 2016) using UTSW POSH referral criteria for comparison of outcomes. Postoperative delirium was assessed via a validated retrospective chart review and cases were confirmed by an expert (SAW). Recognition of delirium was defined as an MD, PA, or NP posing the diagnosis of delirium in the patient chart. RESULTS The mean age at the time of surgery was 73.4 years (UTSW POSH:75.5 years vs control group: 71.5 years; p CONCLUSIONS This study suggests that postoperative delirium is under-recognized in older adults undergoing spine surgery. Enrollment in the UTSW POSH program was associated with a 3-fold increase in the recognition of postoperative delirium by providers and decreased length of stay. Enrollment was associated with a 40% decrease in the incidence of delirium, despite UTSW POSH patients being significantly older and more likely to receive pelvic fixation. Since delirium recognition was not 100% in the UTSW POSH program, additional educational initiatives may be beneficial to further increase recognition and reduce the incidence of delirium. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Modifications in surface glycans attached to proteins via N-acetylglucosamine-β1-N-asparagine linkage have been linked to tumor development and progression. These modifications include complex N-glycans with high levels of branching, fucose and sialic acid residues. Previously, we silenced Mgat2 in neuroblastoma (NB) cells, which halted the conversion of hybrid type N-glycans to complex type, to generate a novel cell line, NB_1(-Mgat2). By comparing the aberrant cell properties of the NB_1(-Mgat2) cell line to the parental cell line (NB_1), we investigated the impact of eliminating complex type N-glycans on NB cell behavior. Further, the N-glycosylation pathway in the NB_1(-Mgat2) cell line was rescued by transiently transfecting cells with Mgat2, thus creating the NB_1(-/+Mgat2) cell line. Changes in the N-glycosylation pathway were verified by enhanced binding of E-PHA and L-PHA to proteins in the rescued cell line relative to those of the NB_1(-Mgat2) cell line. Also, western blotting of total membranes from the rescued cell line ectopically expressing a voltage-gated K+ channel (Kv3.1b) revealed that N-glycans of Kv3.1b were processed to complex type. By employment of various cell lines, we demonstrated that reduction of the complex type N-glycans diminished anchorage-independent cell growth, and enhanced cell-cell interactions. Two independent cell invasion assays showed that cell invasiveness was markedly lessened by lowering the levels of complex type N-glycans while cell mobility was only slightly modified. Neurites of NB cells were shortened by the absence of complex type N-glycans. Cell proliferation was reduced in NB cells with lowered levels of complex type N-glycans which resulted from hindered progression through G1+Go phases of the cell cycle. Overall, our results illustrate that reducing the ratio of complex to hybrid types of N-glycans diminishes aberrant NB cell behavior and thereby has a suppressive effect in cell proliferation, and cell dissociation and invasion phases of NB.

Abnormal modifications in N-glycosylation processing are commonly associated with neurological disorders, although the impact of specific N-glycans on neuronal excitability is unknown. By replacement of complex types of N-glycans with hybrid types in neuroblastoma cells, we provide the first study that addresses how distinct N-glycan types impact neuronal excitability. Using CRISPR/Cas9 technology, NB_1, a clonal cell line derived from rat neuroblastoma cells (NB), was modified to create an N-glycosylation mutant cell line, NB_1 (-Mgat2), which expresses predominantly hybrid type N-glycans. Western and lectin blotting, flow cytometry, TIRF and DIC microscopy, and patch clamp studies were conducted. Lectin binding revealed the predominant type of N-glycans expressed in NB_1 (-Mgat2) is hybrid while those of NB and NB_1 are complex. Kv3.1 b-expressing cells with complex N-glycans localized more glycosylated Kv3.1b to the neurites than cells with hybrid N-glycans. Further the absence of N-glycan attachment to Kv3.1b was critical for sub-plasma distribution of Kv3.1b to neurites in primary adult mammalian neurons, along with NB cells. Replacement of complex type N-glycans with hybrid type hindered the opening and closing rates of outward ionic currents of Kv3.1 b-expressing NB cells. The lacks of N-glycan attachment hindered the rates even more but were not significantly different between the NB cell lines. Taken together, our evidence supports N-glycosylation impacts the sub-plasma membrane localization and activity of Kv3.1 b-containing channels. We propose that N-glycosylation processing of Kv3.1 b-containing channels contributes to neuronal excitability, and abnormal modifications in N-glycosylation processing of Kv3.1b could contribute to neurological diseases.

Highlights • Cell surface N-glycans impact E-cadherin placement at the cell–cell border. • E-cadherin retention at the cell–cell border is affected by cell surface N-glycans. • Cell surface N-glycans influence E-cadherin-mediated cell–cell adhesion. • N-glycans outside the cell contribute to plasma membrane structure., E-cadherin is crucial for adhesion of cells to each other and thereby development and maintenance of tissue. While it is has been established that N-glycans inside the cell impact the level of E-cadherin at the cell surface of epithelial-derived cells, it is unclear whether N-glycans outside the cell control the clustering of E-cadherin at the cell–cell border. Here, we demonstrate reduction of N-glycans at the cell surface weakened the recruitment and retention of E-cadherin at the cell–cell border, and consequently reduced the strength of cell–cell interactions. We conclude that N-glycans at the cell surface are tightly linked to the placement of E-cadherin at the cell–cell border and thereby control E-cadherin mediated cell–cell adhesion.

Glycoconjugates at the cell surface are crucial for cells to communicate with each other and the extracellular microenvironment. While it is generally accepted that glycans are vectorial biopolymers, their information content is unclear. This report provides evidence that distinct N-glycan structures influence the spatial arrangement of two integral membrane glycoproteins, Kv3.1 and E-cadherin, at the adherent membrane which in turn alter cellular properties. Distinct N-glycan structures were generated by heterologous expression of these glycoproteins in parental and glycosylation mutant Chinese hamster ovary cell lines. Unlike the N-linked glycans, the O-linked glycans of the mutant cell lines are similar to those of the parental cell line. Western and lectin blots of total membranes and GFP immunopurified samples, combined with glycosidase digestion reactions, were employed to verify the glycoproteins had predominantly complex, oligomannose, and bisecting type N-glycans from Pro(-)5, Lec1, and Lec10B cell lines, respectively. Based on total internal reflection fluorescence and differential interference contrast microscopy techniques, and cellular assays of live parental and glycosylation mutant CHO cells, we propose that glycoproteins with complex, oligomannose or bisecting type N-glycans relay information for localization of glycoproteins to various regions of the plasma membrane in both a glycan-specific and protein-specific manner, and furthermore cell-cell interactions are required for deciphering much of this information. These distinct spatial arrangements also impact cell adhesion and migration. Our findings provide direct evidence that N-glycan structures of glycoproteins contribute significantly to the information content of cells.

Glycosylation modulates growth, maintenance, and stress signaling processes. Consequently, altered N-glycosylation is associated with reduced fitness and disease. Therefore, expanding our understanding of N-glycans in altering biological processes is of utmost interest. Herein, clustered regularly interspaced short palindromic repeats/caspase9 (CRISPR/Cas9) technology was employed to engineer a glycosylation mutant Chinese Hamster Ovary (CHO) cell line, K16, which expresses predominantly hybrid type N-glycans. This newly engineered cell line enabled us to compare N-glycan effects on cellular properties of hybrid type N-glycans, to the well-established Pro(-)5 and Lec1 cell lines, which express complex and oligomannose types of N-glycans, respectively. Lectin binding studies revealed the predominant N-glycan expressed in K16 is hybrid type. Cell dissociation and migration assays demonstrated the greatest strength of cell-cell adhesion and fastest migratory rates for oligomannose N-glycans, and these properties decreased as oligomannose type were converted to hybrid type, and further decreased upon conversion to complex type. Next, we examined the roles of three general types of N-glycans on ectopic expression of E-cadherin, a cell-cell adhesion protein. Microscopy revealed more functional E-cadherin at the cell-cell border when N-glycans were oligomannose and these levels decreased as the oligomannose N-glycans were processed to hybrid and then to complex. Thus, we provide evidence that all three general types of N-glycans impact plasma membrane architecture and cellular properties.