Summary Mitochondria are essential for neuronal survival and function. Proper degradation of aged and damaged mitochondria through mitophagy is a key cellular pathway for mitochondrial quality control. Recent studies have indicated that PINK1/Parkin-mediated pathways ensure mitochondrial integrity and function [1–8]. Translocation of Parkin to damaged mitochondria induces mitophagy in many non-neuronal cell types [9–16]. However, evidence showing Parkin translocation in primary neurons is controversial [9,15,17,18], leaving unanswered questions as to how and where Parkin-mediated mitophagy occurs in neurons. Here, we report the unique process of dissipating mitochondrial Δψm-induced and Parkin-mediated mitophagy in mature cortical neurons. Compared with non-neuronal cells, neuronal mitophagy is a much slower and compartmentally restricted process, coupled with reduced anterograde mitochondrial transport. Parkin-targeted mitochondria are accumulated in the somatodendritic regions where mature lysosomes are predominantly located. Time-lapse imaging shows dynamic formation and elimination of Parkin- and LC3-ring like structures surrounding depolarized mitochondria through the autophagy-lysosomal pathway in the soma. Knocking down Parkin in neurons impairs the elimination of dysfunctional mitochondria. Thus, our study provides neuronal evidence for dynamic and spatial Parkin-mediated mitophagy, which will help us understand whether altered mitophagy contributes to pathogenesis of several major neurodegenerative diseases characterized by mitochondrial dysfunction and impaired transport.

To understand which organic molecules are capable of binding to gold nanoparticles and/or inducing nanoparticle aggregation, we investigate the interaction of gold nanoparticles with small molecules and amino acids at variable pH. Dynamic Light Scattering (DLS) and ultraviolet-visible (UV-vis) spectra were measured on mixtures of colloidal gold with small molecules to track the progression of the aggregation of gold nanoparticles. We introduce the 522 to 435 nm UV-vis absorbance ratio as a sensitive method for the detection of colloidal gold aggregation, whereby we delineate the ability of thiol, amine, and carboxylic acid functional groups to bind to the surfaces of gold nanoparticles and investigate how combinations of these functional groups affect colloidal stability. We present models for mechanisms of aggregation of colloidal gold, including surface charge reduction and bridging linkers. For all molecules whose addition leads to the aggregation of gold nanoparticles, the aggregation kinetics were accelerated at acidic pH values. Colloidal gold is maintained only in the presence of anionic carboxyl groups, which are neutralized by protonation at lower pH. The overall reduced charge on the stabilizing carboxyl groups accounts for the accelerated aggregation at lower pH values.

OBJECT Improved objective assessments of perioperative risk after spine surgery are necessary to decrease postoperative morbidity and mortality rates. Morphometric analysis has proven utility in predicting postoperative morbidity and mortality in surgical disciplines. The aim of the present study was to evaluate whether morphometrics can be applied to the cases of patients undergoing lumbar spine surgery. METHODS The authors performed a retrospective review of the perioperative course of 395 patients who underwent lumbar surgery at their institution from 2013 to 2014. Preoperative risk factors such as age, diabetes, smoking, coronary artery disease, and body mass index (BMI) were recorded. Preoperative MRI was used to measure the psoas muscle area at the L-4 vertebra and paraspinal muscle area at the T-12 vertebra. Primary outcomes included unplanned return to the operating room, 30- and 90-day readmissions, surgical site infection, wound dehiscence, new neurological deficit, deep vein thrombosis, pulmonary embolism, myocardial infarction, urinary tract infection, urinary retention, hospital-acquired pneumonia, stroke, and prolonged stay in the intensive care unit. RESULTS The overall rate of adverse events was 30%, the most common event being urinary retention (12%). Greater age (p = 0.015) and tobacco usage (p = 0.026) were both significantly associated with complications for all patients, while diabetes, coronary artery disease, and high BMI were not. No surgery-related characteristics were associated with postoperative morbidity, including whether surgery required instrumentation, whether it was a revision, or the number of vertebral levels treated. Using multivariate regression analysis, male and female patients with the lowest psoas tertile had an OR of 1.70 (95% CI 1.04–2.79, p = 0.035) for having postoperative complications. Male patients in the lowest psoas tertile had an OR of 2.42 (95% CI 1.17–5.01, p = 0.016) for having a postoperative complication. The paraspinal muscle groups did not provide any significant data for postoperative morbidity, even after multivariate analysis. CONCLUSIONS The morphometric measurement of psoas muscle size may be a sensitive predictive tool compared with other risk factors for perioperative morbidity in male patients undergoing lumbar surgery.

OBJECTIVEThe inability to significantly improve sagittal parameters has been a limitation of minimally invasive surgery for transforaminal lumbar interbody fusion (MIS TLIF). Traditional cages have a limited capacity to restore lordosis. This study evaluates the use of a crescent-shaped articulating expandable cage (Altera) for MIS TLIF.METHODSThis is a retrospective review of 1- and 2-level MIS TLIF. Radiographic outcomes included differences in segmental and lumbar lordosis, disc height, evidence of fusion, and any endplate violations. Clinical outcomes included the numeric rating scale for leg and back pain and the Oswestry Disability Index (ODI) for low-back pain.RESULTSThirty-nine patients underwent single-level MIS TLIF, and 5 underwent 2-level MIS TLIF. The mean age was 63.1 years, with 64% women. On average, spondylolisthesis was corrected by 4.3 mm (preoperative = 6.69 mm, postoperative = 2.39 mm, p < 0.001), the segmental angle was improved by 4.94° (preoperative = 5.63°, postoperative = 10.58°, p < 0.001), and segmental height increased by 3.1 mm (preoperative = 5.09 mm, postoperative = 8.19 mm, p < 0.001). At 90 days after surgery the authors observed the following: a smaller postoperative sagittal vertical axis was associated with larger changes in back pain at 90 days (r = −0.558, p = 0.013); a larger decrease in spondylolisthesis was associated with greater improvements in ODI and back pain scores (r = −0.425, p = 0.043, and r = −0.43, p = 0.031, respectively); and a larger decrease in pelvic tilt (PT) was associated with greater improvements in back pain (r = −0.548, p = 0.043). For the 1-year PROs, the relationship between the change in PT and changes in ODI and numeric rating scale back pain were significant (r = 0.612, p = 0.009, and r = −0.803, p = 0.001, respectively) with larger decreases in PT associated with larger improvements in ODI and back pain. Overall for this study there was a 96% fusion rate.Fourteen patients were noted to have endplate violation on intraoperative fluoroscopy during placement of the cage. Only 3 of these had progression of their subsidence, with an overall subsidence rate of 6% (3 of 49) visible on postoperative CT.CONCLUSIONSThe use of this expandable, articulating, lordotic, or hyperlordotic interbody cage for MIS TLIF provides a significant restoration of segmental height and segmental lordosis, with associated improvements in sagittal balance parameters. Patients treated with this technique had acceptable levels of fusion and significant reductions in pain and disability.

BACKGROUND While consistently recommended, the significance of early ambulation after surgery has not been definitively studied. OBJECTIVE To identify the relationship between ambulation on the day of surgery (postoperative day (POD)#0) and 90-d adverse events after lumbar surgery. METHODS The Michigan Spine Surgery Improvement Collaborative (MSSIC) is a prospective multicenter registry of spine surgery patients. As part of routine postoperative care, patients either ambulated on POD#0 or did not. The 90-d adverse events of length of stay (LOS), urinary retention (UR), urinary tract infection (UTI), ileus, readmission, surgical site infection (SSI), pulmonary embolism/deep vein thrombosis (PE/DVT), and disposition to a rehab facility were measured. RESULTS A total of 23 295 lumbar surgery patients were analyzed. POD#0 ambulation was associated with decreased LOS (relative LOS 0.83, P &lt; .001), rehab discharge (odds ratio [OR] 0.52, P &lt; .001), 30-d (OR 0.85, P = .044) and 90-d (OR 0.86, P = .014) readmission, UR (OR 0.73, P = 10), UTI (OR 73, P = .001), and ileus (OR 0.52, P &lt; .001) for all patients. Significant improvements in LOS, rehab discharge, readmission, UR, UTI, and ileus were observed in subset analysis of single-level decompressions (4698 pts), multilevel decompressions (4079 pts), single-level fusions (4846 pts), and multilevel fusions (4413 pts). No change in rate of SSI or DVT/PE was observed for patients who ambulated POD#0. CONCLUSION POD#0 ambulation is associated with a significantly decreased risk for several key adverse events after lumbar spine surgery. Decreasing the incidence of these outcomes would be associated with significant cost savings. As ambulation POD#0 is a modifiable factor in any patient's postoperative care following most spine surgery, it should be encouraged and incorporated into spine-related, enhanced-recovery-after-surgery programs.

BACKGROUND Predicting survival of patients with spinal metastases would help stratify treatments from aggressive to palliation. OBJECTIVE To evaluate whether sarcopenia predicts survival in patients with lung, breast, prostate, or multiple myeloma spinal metastases. METHODS Psoas muscle measurements in patients with spinal metastasis were taken from computed tomography scans at 2 time points: at first episode of stereotactic body radiation therapy (SBRT) and from the most recent scan available. Overall survival and hazard ratios were calculated with multivariate cox proportional hazards regression analyses. RESULTS In 417 patients with spinal metastases, 40% had lung cancer, 27% breast, 21% prostate, and 11% myeloma. Overall survival was not associated with age, sex, ethnicity, levels treated, or SBRT volume. Multivariate analysis showed patients in the lowest psoas tertile had shorter survival (222 d, 95% CI = 185-323 d) as compared to the largest tertile (579 d, 95% CI = 405-815 d), (HR1.54, P = .005). Median psoas size as a cutoff value was also strongly predictive for survival (HR1.48, P = .002). Survival was independent of tumor histology. The psoas/vertebral body ratio was also successful in predicting overall survival independent of tumor histology and gender (HR1.52, P &lt; .01). Kaplan–Meier survival curves visually represent survival (P = .0005). CONCLUSION In patients with spine metastases, psoas muscle size as a hallmark of frailty/sarcopenia is an objective, simple, and effective way to identify patients who are at risk for shorter survival, regardless of tumor histology. This information can be used to help with surgical decision making in patients with advanced cancer, as patients with small psoas sizes are at higher risk of death.

BACKGROUND Novel methods in predicting survival in patients with spinal metastases may help guide clinical decision-making and stratify treatments regarding surgery vs palliative care. OBJECTIVE To evaluate whether the frailty/sarcopenia paradigm is predictive of survival and morbidity in patients undergoing surgery for spinal metastasis. METHODS A total of 271 patients from 4 tertiary care centers who had undergone surgery for spinal metastasis were identified. Frailty/sarcopenia was defined by psoas muscle size. Survival hazard ratios were calculated using multivariate analysis, with variables from demographic, functional, oncological, and surgical factors. Secondary outcomes included improvement of neurological function and postoperative morbidity. RESULTS Patients in the smallest psoas tertile had shorter overall survival compared to the middle and largest tertile. Psoas size (PS) predicted overall mortality more strongly than Tokuhashi score, Tomita score, and Karnofsky Performance Status (KPS). PS predicted 90-d mortality more strongly than Tokuhashi score, Tomita score, and KPS. Patients with a larger PS were more likely to have an improvement in deficit compared to the middle tertile. PS was not predictive of 30-d morbidity. CONCLUSION In patients undergoing surgery for spine metastases, PS as a surrogate for frailty/sarcopenia predicts 90-d and overall mortality, independent of demographic, functional, oncological, and surgical characteristics. The frailty/sarcopenia paradigm is a stronger predictor of survival at these time points than other standards. PS can be used in clinical decision-making to select which patients with metastatic spine tumors are appropriate surgical candidates.

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