Late-week Multilevel Anterior Cervical Discectomy and Fusion Associated with Increased Length of Stay.

STUDY DESIGN: Retrospective analysis of clinical data from a single institution. OBJECTIVE: To assess the day of surgery during the week as a possible predictor of length of stay (LOS) following anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Surgeries later in the week may result in longer LOS and higher costs for joint arthroplasty, yet this is unclear following spine surgery. Procedures performed later in the week may lead to weekend admissions when there are limited services that may contribute to an extended LOS. We attempt to identify associations between day of surgery and LOS, readmission, and complications following single- and multilevel ACDF. MATERIALS AND METHODS: Patients at a single institution undergoing ACDF by 7 primary surgeons in both orthopedic and neurosurgery spine departments between 2015 and 2019 were retrospectively reviewed. Patients were stratified by surgery day at either the beginning (Monday/Tuesday) or end (Thursday/Friday) of the week and by single- or multilevel ACDF. Surgery for trauma, infections, adjacent level disease, or revision were excluded. Patient demographics, Charlson Comorbidity Index (CCI), LOS, postoperative complications, and readmission rates were assessed. RESULTS: Six hundred fifty-two patients underwent ACDF. For single-level ACDF, 222 were reviewed, with 112 having surgery at the beginning and 110 at the end of the week. For multilevel ACDF, 431 were reviewed, with 192 having surgery at the beginning and 239 at the end of the week. No differences in pre- or postoperative variables were determined for single-level ACDF. Despite no differences in pre-operative variables, CCI, operative duration, or number of levels, late-week multilevel ACDF had longer average LOS (2.8±3.0 days) compared to early-week surgery (2.0±2.0 days) (P=0.018). CONCLUSIONS: Late-week multilevel ACDF was associated with an increased LOS, as it may prove beneficial to surgical planning. This conflicts with previous reports that day of week was not associated with LOS following ACDF. LEVEL OF EVIDENCE: III.

Choline supplementation mitigates effects of bilirubin in cerebellar granule neurons in vitro.

BACKGROUND: Premature infants may suffer from high levels of bilirubin that could lead to neurotoxicity. Bilirubin has been shown to decrease L1-mediated ERK1/2 signaling, L1 phosphorylation, and L1 tyrosine 1176 dephosphorylation. Furthermore, bilirubin redistributes L1 into lipid rafts (LR) and decreases L1-mediated neurite outgrowth. We demonstrate that choline supplementation improves L1 function and signaling in the presence of bilirubin. METHODS: Cerebellar granule neurons (CGN) were cultured with and without supplemental choline, and the effects on L1 signaling and function were measured in the presence of bilirubin. L1 activation of ERK1/2, L1 phosphorylation and dephosphorylation were measured. L1 distribution in LR was quantified and neurite outgrowth of CGN was determined. RESULTS: Forty µM choline significantly reduced the effect of bilirubin on L1 activation of ERK1/2 by 220% (p = 0.04), and increased L1 triggered changes in tyrosine phosphorylation /dephosphorylation of L1 by 34% (p = 0.026) and 35% (p = 0.02) respectively. Choline ameliorated the redistribution of L1 in lipid rafts by 38% (p = 0.02) and increased L1-mediated mean neurite length by 11% (p = 0.04). CONCLUSION: Choline pretreatment of CGN significantly reduced the disruption of L1 function by bilirubin. The supplementation of pregnant women and preterm infants with choline may increase infant resilience to the effects of bilirubin. IMPACT: This article establishes choline as an intervention for the neurotoxic effects of bilirubin on lipid rafts. This article provides clear evidence toward establishing one intervention for bilirubin neurotoxicity, where little is understood. This article paves the way for future investigation into the mechanism of the ameliorative effect of choline on bilirubin neurotoxicity.

Rarely tested or treated but highly prevalent: Hypercholesterolemia in ED observation unit patients with chest pain.

BACKGROUND: Hypercholesterolemia (HCL) is common among Emergency Department (ED) patients with chest pain but is typically not addressed in this setting. This study aims to determine whether a missed opportunity for Emergency Department Observation Unit (EDOU) HCL testing and treatment exists. METHODS: We conducted a retrospective observational cohort study of patients ≥18 years old evaluated for chest pain in an EDOU from 3/1/2019-2/28/2020. The electronic health record was used to determine demographics and if HCL testing or treatment occurred. HCL was defined by self-report or clinician diagnosis. Proportions of patients receiving HCL testing or treatment at 1-year following their ED visit were calculated. HCL testing and treatment rates at 1-year were compared between white vs. non-white and male vs. female patients using multivariable logistic regression models including age, sex, and race. RESULTS: Among 649 EDOU patients with chest pain, 55.8% (362/649) had known HCL. Among patients without known HCL, 5.9% (17/287, 95% CI 3.5-9.3%) had a lipid panel during their index ED/EDOU visit and 26.5% (76/287, 95% CI 21.5-32.0%) had a lipid panel within 1-year of their initial ED/EDOU visit. Among patients with known or newly diagnosed HCL, 54.0% (229/424, 95% CI 49.1-58.8%) were on treatment within 1-year. After adjustment, testing rates were similar among white vs. non-white patients (aOR 0.71, 95% CI 0.37-1.38) and men vs. women (aOR 1.32, 95% CI 0.69-2.57). Treatment rates were similar among white vs. non-white (aOR 0.74, 95% CI 0.53-1.03) and male vs. female (aOR 1.08, 95% CI 0.77-1.51) patients. CONCLUSIONS: Few patients were evaluated for HCL in the ED/EDOU or outpatient setting after their ED/EDOU encounter and only 54% of patients with HCL were on treatment during the 1-year follow-up period after the index ED/EDOU visit. These findings suggest a missed opportunity to reduce cardiovascular disease risk exists by evaluating and treating HCL in the ED or EDOU.

Bilirubin inhibits lipid raft dependent functions of L1 cell adhesion molecule in rat pup cerebellar granule neurons.

BACKGROUND: The mechanism of bilirubin neurotoxicity is poorly understood. We hypothesize that bilirubin inhibits the function of lipid rafts (LR), microdomains of the plasma membrane critical for signal transduction. To test this hypothesis, we measured the effect of free bilirubin (Bf) between 7.6 and 122.5 nM on LR-dependent functions of L1 cell adhesion molecule (L1). METHODS: Cerebellar granule neurons (CGN) were plated on poly-L-lysine overnight, and neurite length was determined after 1 h treatment with L1 alone or L1 and bilirubin. L1 activation of ERK1/2 was measured in CGN in the presence or absence of bilirubin. The effect of bilirubin on L1 distribution in LR was quantitated, and the localization of bilirubin to LR was determined. RESULTS: The addition of bilirubin to CGN treated with L1 significantly decreased neurite length compared to L1 alone. L1 activation of ERK1/2 was inhibited by bilirubin. Bilirubin redistributed L1 into LR. Bilirubin was associated only with LR-containing fractions of a sucrose density gradient. CONCLUSION: Bf significantly inhibits LR-dependent functions of L1 and are found only associated with LR, suggesting one mechanism by which bilirubin may exert neurotoxicity is through the dysfunction of protein-LR interactions. IMPACT: This article establishes lipid rafts as a target for the neurotoxic effects of bilirubin. This article provides clear evidence toward establishing one mechanism of bilirubin neurotoxicity, where little is understood. This article paves the way for future investigation into lipid raft dependent functions, and its role in neurodevelopmental outcome.