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 nonneuronal 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 nonneuronal 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.
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► Depolarized mitochondria recruit exogenous/endogenous Parkin in mature cortical neurons ► Parkin translocation occurs predominantly in the somatodendritic region ► Dynamic elimination of Parkin and LC3-targeted depolarized mitochondria in the soma ► Knocking down Parkin in neurons impairs the elimination of dysfunctional mitochondria
Abstract
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 < .001), rehab discharge (odds ratio OR 0.52, P < .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 < .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.
Abstract
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 < .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.
Abstract
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.
Graphical Abstract
Graphical Abstract
•Mean distance ambulated upon first interaction with physical therapy was longest among patients discharged on the postoperative day (POD) 1 group and significantly decreased to POD 2 and POD ≥ 3 ...group.•The odds of longer length of stay decreased by 35% for every 50 ft ambulated.•Patient-reported outcomes (PROs) did not differ among the three cohorts. Preoperative Oswestry Disability Index (ODI) failed to predict time to discharge in the logistical regression analysis.
With a lesser degree of tissue destruction, patients undergoing minimally-invasive spine surgery are primed to benefit from early mobilization, which can further enhance recovery and hasten rehabilitation. We aimed to determine the role of physical therapy on earlier discharge after minimally-invasive transforaminal lumbar interbody fusion (TLIF).
Michigan Spine Surgery Improvement Collaborative (MSSIC) provided patients undergoing one- and two-level minimally-invasive TLIF for degenerative lumbar disease. The study population was divided into patients with a one-day length of stay (LOS 1), two days (LOS 2), and three or more days (LOS ≥ 3) to maintain three equal-time cohorts. On POD 0, physical therapy (or, in very rare circumstances, a spine-care-specialized nurse in patients arriving to the in-patient floors late after hours) must evaluate capacity to ambulate.
Of the 101 patients, the median day of first ambulation statistically significantly increased from the LOS 1 to LOS ≥ 3 cohort (P = 0.007). Mean distance ambulated decreased from 156.5 ± 123.1 feet in the LOS 1 group, 108.9 ± 83.9 feet in the LOS 2 group, to 69.2 ± 58.3 feet in the LOS ≥ 3 group (P = 0.002). Patient-reported outcomes did not differ among the three cohorts. Following a multivariable ordinal logistical regression controlling for disposition to rehab over home (ORadj = 5.47, P = 0.045), the odds of longer LOS decreased by 39% for every 50-feet ambulated (P = 0.002).
Time to first ambulation independently increases the odds of earlier discharge, regardless of comorbidity burden and surgical determinants.
Proper degradation of aged and damaged mitochondria through mitophagy is essential to ensure mitochondrial integrity and function. Translocation of PARK2/Parkin onto damaged mitochondria induces ...mitophagy in many non-neuronal cell types. However, direct evidence showing PARK2-mediated mitophagy in mature neurons is controversial, leaving unanswered questions as to how, where, and by what time course PARK2-mediated mitophagy occurs in neurons following mitochondrial depolarization. We applied long time-lapse imaging in live mature cortical neurons to monitor the slow but dynamic and spatial PARK2 translocation onto damaged mitochondria and subsequent degradation through the autophagy-lysosomal pathway. In comparison with non-neuronal cells, our study reveals unique features of PARK2-mediated mitophagy in mature neurons, which will advance our understanding of pathogenesis of several major neurodegenerative diseases characterized by damaged mitochondria or a dysfunctional autophagy-lysosomal system.
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.
Intraspinal dermoid tumors are usually rare benign growths that occur as a result of defects during neural tube formation. They make up less than 1% of tumors in the spine and are associated with ...spinal dysraphisms or sinus tracts. Although rare, malignant transformation into squamous cell carcinoma has been previously reported. Malignant transformation into adenocarcinoma, however, represents a novel phenotypic differentiation pattern that is hitherto undescribed.
A 45-year-old woman presented with acute symptoms of cauda equina syndrome. Imaging of the spine revealed a large intradural sacral mass. The lesion was surgically resected with pathology revealing a dermoid tumor with malignant transformation into adenocarcinoma. Metastatic workup revealed no other suspicious lesions. The patient had an uneventful postoperative course, gradually regaining micturition control.
Dermoid tumors, also known as benign cystic teratoma or mature teratoma, are usually benign congenital tumors comprising epithelial cells that arise from displaced embryonic ectoderm and mesoderm during neural tube formation. Although extremely rare, malignant transformation into squamous cell carcinoma has been reported. This case represents the first report of an intraspinal dermoid tumor transforming into adenocarcinoma. A comprehensive histopathologic analysis is key to identifying the lesion and guiding postsurgical management.
The current standard of care for prediction of survival of cancer staging is based on TNM staging. However, for patients with spinal metastasis, who all have identical stage IV disease, identifying ...accurate prognostic markers of survival would allow better treatment stratification between more aggressive treatment strategies or palliation. Analytical morphometrics enables physicians to quantify patient frailty by measuring lean muscle mass. Morphometrics also predicts survival in patients with lung cancer metastases to the spine.
Our study evaluates whether morphometrics is predictive of survival in patients with breast cancer spinal metastasis.
This is an observational retrospective cohort study.
This study includes female patients with breast cancer spinal metastases and patients who have undergone stereotactic body radiation therapy.
Overall survival was the primary outcome measure.
Morphometric measurements of the psoas muscle were taken using computed tomography scans of the lumbar spine. We then stratified patients into tertiles based on the psoas muscle area.
We identified 118 patients, with a median survival of 104 days (95% confidence interval CI=73–157 days). Overall survival was not associated with age, chemotherapy, or number of levels radiated. Patients in the lowest tertile of psoas size had significantly shorter survival compared with the highest tertile (68 days versus 148 days, hazard ratio 1.76 95% CI=1.08–2.89, p=.024). The shorter survival was also true for the lowest tertile versus the middle tertile (68 days versus 167 days, hazard ratio 1.95 95% CI=1.19–3.19, p=.007). Kaplan-Meier survival curves were used to visually illustrate the differences in survival between different tertiles.
Morphometric analysis of the psoas muscle size in patients with breast cancer metastases to the spine was effective in identifying patients at risk of shorter survival. Further research is needed to validate these results, as well as to see if these methodologies can be applied to other cancer histologies.
OBJECTIVE Predicting the survival rate for patients with cancer is currently performed using the TNM Classification of Malignant Tumors (TNM). Identifying accurate prognostic markers of survival ...would allow better treatment stratification between more aggressive treatment strategies or palliation. This is especially relevant for patients with spinal metastases, who all have identical TNM staging and whose surgical decision-making is potentially complex. Analytical morphometrics quantifies patient frailty by measuring lean muscle mass and can predict risk for postoperative morbidity after lumbar spine surgery. This study evaluates whether morphometrics can be predictive of survival in patients with spinal metastases. METHODS Utilizing a retrospective registry of patients with spinal metastases who had undergone stereotactic body radiation therapy, the authors identified patients with primary lung cancer. Morphometric measurements were taken of the psoas muscle using CT of the lumbar spine. Additional morphometrics were taken of the L-4 vertebral body. Patients were stratified into tertiles based on psoas muscle area. The primary outcome measure was overall survival, which was measured from the date of the patient's CT scan to date of death. RESULTS A total of 168 patients were identified, with 54% male and 54% having multiple-level metastases. The median survival for all patients was 185.5 days (95% confidence interval CI 146-228 days). Survival was not associated with age, sex, or the number of levels of metastasis. Patients in the smallest tertile for the left psoas area had significantly shorter survival compared with a combination of the other two tertiles: 139 days versus 222 days, respectively, hazard ratio (HR) 1.47, 95% CI 1.06-2.04, p = 0.007. Total psoas tertiles were not predictive of mortality, but patients whose total psoas size was below the median size had significantly shorter survival compared with those greater than the median size: 146 days versus 253.5 days, respectively, HR 1.43, 95% CI 1.05-1.94, p = 0.025. To try to differentiate small body habitus from frailty, the ratio of psoas muscle area to vertebral body area was calculated. Total psoas size became predictive of mortality when normalized to vertebral body ratio, with patients in the lowest tertile having significantly shorter survival (p = 0.017). Left psoas to vertebral body ratio was also predictive of mortality in patients within the lowest tertile (p = 0.021). Right psoas size was not predictive of mortality in any calculations. CONCLUSIONS In patients with lung cancer metastases to the spine, morphometric analysis of psoas muscle and vertebral body size can be used to identify patients who are at risk for shorter survival. This information should be used to select patients who are appropriate candidates for surgery and for the tailoring of oncological treatment regimens.
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