Short non-coding RNA sequencing of glioblastoma extracellular vesicles.

INTRODUCTION: Like all nucleated cells, glioblastoma (GBM) cells shed small membrane-encapsulated particles called extracellular vesicles (EVs). EVs can transfer oncogenic components and promote tumor growth by transferring short non-coding RNAs, altering target cell gene expression. Furthermore, GBM-derived EVs can be detected in blood and have potential to serve as liquid biopsies. METHODS: EVs were harvested from culture supernatants from human GBM cell lines, purified via sequential centrifugation, and quantified by nanoparticle tracking. RNA was isolated and short non-coding RNA was sequenced. Data was analyzed via the OASIS-2.0 platform using HG38. MirTarBase and MirDB interrogated validated/predicted miRNA-gene interactions respectively. RESULTS: Many short non-coding RNA's were identified within GBM EV's. In keeping with earlier reports utilizing GBM EV micro-RNA (miRNA) arrays, these included abundant micro-RNA's including miR-21. However, RNA sequencing revealed a total of 712 non-coding RNA sequences most of which have not been associated with GBM EV's previously. These included many RNA species (piRNA, snoRNA, snRNA, rRNA and yRNAs) in addition to miRNA's. miR-21-5p, let-7b-5p, miR-3182, miR-4448, let-7i-5p constituted highest overall expression. Top genes targeted by non-coding RNA's were highly conserved and specific for cell cycle, PI3K/Akt signaling, p53 and Glioma curated KEGG pathways. CONCLUSIONS: Next generation short non-coding RNA sequencing on GBM EV's validates findings from earlier studies using miRNA arrays but also demonstrates expression of many additional non-coding RNA sequences and classes previously unassociated with GBM. This may yield important insights into pathophysiology, point to new therapeutic targets, and help develop new biomarkers for disease burden and treatment response.

Diabetes and Back Pain: Markers of Diabetes Disease Progression Are Associated With Chronic Back Pain.

IN BRIEF Diabetes has been associated with the incidence of back pain. However, the relationship between markers of diabetes progression and back pain has not been studied. The objective of this study was to correlate clinical and laboratory measures of diabetes disease severity to the presence of back pain to provide insight into the relationship between these conditions. Findings showed that markers of diabetes disease progression were associated with the presence of back pain, suggesting that uncontrolled diabetes may contribute to the development of chronic back pain.

Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries.

With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140-178 days irrespective of the number of SRS(s) (interquartile range 60-300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).

The comparative effectiveness of surgeons over interventionalists in endovascular repairs of abdominal aortic aneurysm.

OBJECTIVE: Comparative effectiveness research has mostly been focused on comparison of treatment techniques. The goal of the present study was to extend the research to physician specialty. BACKGROUND: Both surgeons and interventionalists (cardiologists and radiologists) are involved in endovascular repairs (EVAR) of aortic aneurysms, with different residency education, operative experience, preoperative assessment and patient selection, and postoperative continuity of care. METHODS: Retrospective analysis was performed using the Nationwide Inpatient Sample from 1998 to 2009. Patients undergoing EVAR for abdominal aortic aneurysm were identified with International Classification of Diseases, Ninth Revision, procedure code 39.71. Using physician identifiers available in the database, surgeons were identified by case experience in the same calendar year with elective open AAA repairs, arteriovenous fistula repairs, or carotid endarderectomy. Multivariate analysis adjusted for physician volume, AAA ruptured status, patient demographic and comorbidities, and hospital characteristics. RESULTS: A total of 28,094 EVARs were analyzed. Unadjusted mortality rates, length of stay, and total hospital charges were significantly higher for patients treated by interventionalists than those by surgeons (all Ps < 0.001). This difference persisted on multivariate analysis, where interventionalists were associated with increased likelihood of mortality (odds ratio = 1.39; 95% confidence interval, 1.04-1.89), longer length of stay (1.32 days; 95% confidence interval, 1.03-1.62), and higher total hospital charges ($19,312; 95% confidence interval, 16,471-22,153). CONCLUSIONS: Physician specialty is associated with patient outcomes. Surgeons are associated with improved outcomes, with lower mortality, shorter length of stay, and lower charges for EVAR cases, when compared with interventionalists. This finding has significant implications for future comparative effectiveness research and potential policy changes in patient referrals or physician admitting privileges.

Surgical technique and recurrence in cholesteatoma: a meta-analysis.

Conflicting reports and surgeon opinions have contributed to a long-standing debate regarding the merits of the intact canal wall versus canal wall down approach to cholesteatoma. The objective of this analysis was to identify and synthesize available data concerning rates of recidivism after the two primary types of cholesteatoma surgery. PubMed, Cochrane Collaboration, and Google Scholar searches were performed and articles filtered based on predetermined exclusion criteria. Individually reported rates of recurrent and residual disease were extracted and recorded. Meta-analysis demonstrated a relative risk of 2.87 with a confidence interval of 2.45-3.37, confirming a significantly increased incidence of postoperative cholesteatoma when using an intact canal wall approach rather than a canal wall down approach. Next, rates of recidivism following the typical two-stage intact canal wall operation were compared with a single-stage canal wall down operation and found to be similar. In conclusion, we advocate that greater consideration should be given to the canal wall down procedure in initial surgical management and identify the need for further exploration of rates of recidivism after staged or second-look procedures.

Can machine learning algorithms accurately predict discharge to nonhome facility and early unplanned readmissions following spinal fusion? Analysis of a national surgical registry.

OBJECTIVE: Nonhome discharge and unplanned readmissions represent important cost drivers following spinal fusion. The authors sought to utilize different machine learning algorithms to predict discharge to rehabilitation and unplanned readmissions in patients receiving spinal fusion. METHODS: The authors queried the 2012-2013 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) for patients undergoing cervical or lumbar spinal fusion. Outcomes assessed included discharge to nonhome facility and unplanned readmissions within 30 days after surgery. A total of 7 machine learning algorithms were evaluated. Predictive hierarchical clustering of procedure codes was used to increase model performance. Model performance was evaluated using overall accuracy and area under the receiver operating characteristic curve (AUC), as well as sensitivity, specificity, and positive and negative predictive values. These performance metrics were computed for both the imputed and unimputed (missing values dropped) datasets. RESULTS: A total of 59,145 spinal fusion cases were analyzed. The incidence rates of discharge to nonhome facility and 30-day unplanned readmission were 12.6% and 4.5%, respectively. All classification algorithms showed excellent discrimination (AUC > 0.80, range 0.85-0.87) for predicting nonhome discharge. The generalized linear model showed comparable performance to other machine learning algorithms. By comparison, all models showed poorer predictive performance for unplanned readmission, with AUC ranging between 0.63 and 0.66. Better predictive performance was noted with models using imputed data. CONCLUSIONS: In an analysis of patients undergoing spinal fusion, multiple machine learning algorithms were found to reliably predict nonhome discharge with modest performance noted for unplanned readmissions. These results provide early evidence regarding the feasibility of modern machine learning classifiers in predicting these outcomes and serve as possible clinical decision support tools to facilitate shared decision making.

A1 segment hypoplasia associated with cerebral infarction after anterior communicating artery aneurysm rupture.

BACKGROUND: Congenital hypoplasia or absence of the A1 segment of the anterior cerebral artery (ACA) has been associated with increased incidence of berry aneurysms at the anterior communicating artery (Acom) complex. It is not known, however, whether this anatomic variant also predisposes patients to complications after aneurysmal subarachnoid hemorrhage. METHODS: Patients were included for analysis if they presented to our institution for clipping or coiling of an Acom aneurysm between the years of 2001 and 2013. Patients were deemed to have cerebral infarction if a new hypodensity in a vascular distribution was visualized on CT imaging. The association between A1 segmental abnormalities and radiologic infarction was subsequently evaluated in a risk-adjusted manner using stepwise multivariable logistic regression analysis. RESULTS: Of 145 patients who presented with aneurysmal subarachnoid hemorrhage after rupture of an Acom aneurysm, 31 (21.4%) had a hypoplastic or absent A1 segment. On univariate analysis, there was a trend toward an increased rate of radiologic infarction in patients with A1 segment abnormalities (OR=2.11, 95% CI: 0.93-4.79; P=0.0757). On multivariable analysis, a hypoplastic or absent A1 segment was significantly associated with an increased rate of radiologic infarction (OR=2.54, 95% CI: 1.02-6.43; P=0.0466). CONCLUSIONS: Our results suggest that a hypoplastic or absent A1 segment is associated with cerebral infarction following subarachnoid hemorrhage from ruptured Acom aneurysms, indicating a potential need for heightened vigilance and a reduced threshold for therapeutic intervention in patients harboring this abnormality.

Allograft versus autograft in cervical and lumbar spinal fusions: an examination of operative time, length of stay, surgical site infection, and blood transfusions.

BACKGROUND: Autograft harvesting for spine arthrodesis has been associated with longer operative times and increased blood loss. Allograft compared to autograft in spinal fusions has not been studied in a multicenter cohort. METHODS: Patients enrolled in the ACS-NSQIP registry between 2012 and 2013 who underwent cervical or lumbar spinal fusion with either allograft or autograft through a separate incision were included for analysis. The primary outcomes of interest were operative time, length of stay, blood transfusion, and surgical site infection (SSI). RESULTS: A total of 6790 and 6718 patients received a cervical or lumbar spinal fusion, respectively. On unadjusted analysis in both cervical and lumbar cohorts, autograft was associated with increased rates of blood transfusion (cervical: 2.9% vs. 1.0%, P<0.001; and lumbar: 21.0% vs. 15.7%, P<0.001) and increased operative time (cervical: 167 vs. 128 minutes, P<0.001; and lumbar: 226 vs. 204 minutes, P<0.001) relative to allograft. On multivariable analysis in both the cervical and lumbar cohorts, autograft was associated with increased odds of blood transfusion (cervical: OR=2.3, 95% CI: 1.0-5.1; and lumbar: OR=1.3, 95% CI: 1.1-1.6) and longer operative times (cervical: 27.8 minutes, 95% CI: 20.7-35.0; and lumbar: 25.4 minutes, 95% CI: 17.7-33.1) relative to allograft. Autograft was not associated with either length of stay or SSI. CONCLUSIONS: In a multicenter cohort of patients undergoing cervical or lumbar spinal fusion, autograft was associated with increased rates of blood transfusion and increased operative time relative to allograft.

Radiation-Induced Cavernous Malformations After Single-Fraction Meningioma Radiosurgery.

BACKGROUND: Stereotactic radiosurgery (SRS) is a commonly performed procedure for patients with intracranial meningiomas. OBJECTIVE: To describe the clinical features of patients with radiation-induced cavernous malformations (RICM) after single-fraction meningioma SRS. METHODS: Retrospective study of patients having single-fraction SRS for intracranial meningioma at our center from 1990 through 2009, and 1 patient who had single-fraction SRS elsewhere. Patients were excluded if they refused research authorization (n = 7), had a World Health Organization Grade II or III meningioma (n = 65), had a genetic predisposition for tumor development (n = 52), had prior or concurrent radiation therapy (n = 49), or had less than 2 yr of magnetic resonance imaging follow-up after SRS (n = 77). The median follow-up of the remaining 426 patients was 7.9 yr (range, 2-24.9). RESULTS: Three RICM (0.7%) were identified at 2, 10, and 21 yr after SRS. Two patients were asymptomatic, whereas 1 patient had a brainstem hemorrhage causing facial weakness and numbness. The risk of developing an RICM after SRS was 0.2% at 5 yr and 0.9% at 15 yr. All patients were observed and remained stable without additional bleeding in follow-up of 7, 12.8, and 2 yr, respectively. A fourth patient developed progressive neurological dysfunction starting 7 yr after SRS at another center and was treated for several years with bevacizumab without improvement. Surgical resection was performed 11.5 yr after SRS and histologic examination was consistent with an RICM. CONCLUSION: The risk of RICM after single-fraction SRS for intracranial meningiomas is very low, but the latency period noted until their detection emphasizes the need for extended imaging follow-up after SRS of benign lesions.

Risk Factors for Readmission with Cerebrospinal Fluid Leakage Within 30 Days of Vestibular Schwannoma Surgery.

BACKGROUND: Cerebrospinal fluid (CSF) leak is a well-recognized complication after surgical resection of vestibular schwannomas and is associated with a number of secondary complications, including readmission and meningitis. OBJECTIVE: To identify risk factors for and timing of 30-d readmission with CSF leak. METHODS: Patients who had undergone surgical resection of a vestibular schwannoma from 1995 to 2010 were identified in the California Office of Statewide Health Planning and Development database. The most common admission diagnoses were identified by International Classification of Disease, ninth Revision, diagnosis codes, and predictors of readmission with CSF leak were determined using logistic regression. RESULTS: A total of 6820 patients were identified. CSF leak, though a relatively uncommon cause of admission after discharge (3.52% of all patients), was implicated in nearly half of 490 readmissions (48.98%). Significant independent predictors of readmission with CSF leak were male sex (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.32-2.25), first admission at a teaching hospital (OR 3.32, 95% CI 1.06-10.39), CSF leak during first admission (OR 1.84, 95% CI 1.33-2.55), obesity during first admission (OR 2.10, 95% CI 1.20-3.66), and case volume of first admission hospital (OR of log case volume 0.82, 95% CI 0.70-0.95). Median time to readmission was 6 d from hospital discharge. CONCLUSION: This study has quantified CSF leak as an important contributor to nearly half of all readmissions following vestibular schwannoma surgery. We propose that surgeons should focus on technical factors that may reduce CSF leakage and take advantage of potential screening strategies for the detection of CSF leakage prior to first admission discharge.

Paraneoplastic syndrome or metastatic sinonasal neuroendocrine carcinoma? Clinical conundrum.

We report a case of a middle-aged woman with a diffuse, nonenhancing, progressively atrophic T2-hyperintense lesion involving the left frontotemporal lobes and insula found to be synchronous high-grade sinonasal neuroendocrine carcinoma (SNEC) after initial endonasal resection. In 2014, a 47-year old woman underwent resection of a left-sided high-grade ethmoidal neuroendocrine carcinoma after presentation with weight gain and increased levels of serum and urine cortisol. Concurrent with the initial presentation, she was noted to have a nonenhancing, hyperintense signal change on T2-weighted images on the left frontotemporal lobes and insula thought to be paraneoplastic. Moreover, low titer antibodies to voltage-gated potassium channels were present, raising concern for limbic encephalitis. However, the patient was asymptomatic. A little more than a year after initial presentation, she noted excessive fatigue, daytime somnolence, and cognitive decline. Imaging revealed a gradually progressive, nonenhancing, T2-hyperintense signal abnormality with progressive atrophy in the left anteroinferior frontal lobe, anteromedial temporal lobe, insula bilateral cingulate gyri, and bilateral thalami. Given the progressive nature of the abnormality, stereotactic biopsy was performed, which confirmed the lesion to be metastatic, infiltrative SNEC. In summary, this is a rare case of a synchronous presentation of a high-grade SNEC with an unusual appearance that diffusely infiltrated the brain, likely directly involving the left olfactory nerve and spreading along olfactory projections. This case draws physicians' attention to the possibility that although paraneoplastic syndromes are most likely benign, dissemination of the primary cancer is a diagnostic possibility.

Impact of neurosurgeon specialization on patient outcomes for intracranial and spinal surgery: a retrospective analysis of the Nationwide Inpatient Sample 1998-2009.

OBJECTIVE The subspecialization of neurosurgical practice is an ongoing trend in modern neurosurgery. However, it remains unclear whether the degree of surgeon specialization is associated with improved patient outcomes. The authors hypothesized that a trend toward increased neurosurgeon specialization was associated with improved patient morbidity and mortality rates. METHODS The Nationwide Inpatient Sample (NIS) was used (1998-2009). Patients were included in a spinal analysis cohort for instrumented spine surgery involving the cervical spine ( International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 81.31-81.33, 81.01-81.03, 84.61-84.62, and 84.66) or lumbar spine (codes 81.04-81.08, 81.34-81.38, 84.64-84.65, and 84.68). A cranial analysis cohort consisted of patients receiving a parenchymal excision or lobectomy operation (codes 01.53 and 01.59). Surgeon specialization was measured using unique surgeon identifiers in the NIS and defined as the proportion of a surgeon's total practice dedicated to cranial or spinal cases. RESULTS A total of 46,029 and 231,875 patients were identified in the cranial and spinal analysis cohorts, respectively. On multivariate analysis in the cranial analysis cohort (after controlling for overall surgeon volume, patient demographic data/comorbidities, hospital characteristics, and admitting source), each percentage-point increase in a surgeon's cranial specialization (that is, the proportion of cranial cases) was associated with a 0.0060 reduction in the log odds of patient mortality (95% CI 0.0034-0.0086) and a 0.0042 reduction in the log odds of morbidity (95% CI 0.0032-0.0052). This resulted in a 15% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of cranial specialization. In the spinal analysis cohort, each percentage-point increase in a surgeon's spinal specialization was associated with a 0.0122 reduction in the log odds of mortality (95% CI 0.0074-0.0170) and a 0.0058 reduction in the log odds of morbidity (95% CI 0.0049-0.0067). This resulted in a 26.8% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of spinal specialization. CONCLUSIONS For both spinal and cranial surgery patient cohorts derived from the NIS database, increased surgeon specialization was significantly and independently associated with improved mortality and morbidity rates, even after controlling for overall case volume.

Thirty-day postoperative morbidity and mortality after temporal lobectomy for medically refractory epilepsy.

OBJECTIVE Temporal lobectomy is a well-established treatment modality for the management of medically refractory epilepsy in appropriately selected patients. The aim of this study was to assess 30-day morbidity and mortality after temporal lobectomy in cases registered in a national database. METHODS A retrospective cohort analysis was conducted using a multiinstitutional surgical registry compiled between 2006 and 2014. The authors identified patients who underwent anterior temporal lobectomy and/or amygdalohippocampectomy for a primary diagnosis of intractable epilepsy. Univariate and multivariable analyses with regard to patient demographics, comorbidities, operative characteristics, and 30-day outcomes were applied. RESULTS A total of 216 patients were included in the study. The median age was 38 years and 46% of patients were male. The median length of stay was 3 days and the 30-day mortality rate was 1.4%. Fourteen patients (6.5%) developed at least one major complication. Return to the operating room was observed in 7 patients (3.2%). Readmission within 30 days and discharge to a location other than home were available for 2011-2014 (n = 155) and occurred in 11% and 10.3% of patients, respectively. Multivariable regression analysis revealed that increasing age was an independent predictor of discharge disposition other than home and that male sex was a significant risk factor for the development of a major complication. Interestingly, the presence of the attending neurosurgeon and a resident during the procedure was significantly associated with decreased odds of prolonged length of stay (i.e., > 75th percentile [5 days]) and discharge to a location other than home. CONCLUSIONS Using a multiinstitutional surgical registry, 30-day outcome data after temporal lobectomy for medically intractable epilepsy demonstrates a mortality rate of 1.4%, a major complication rate of 6.5%, and a readmission rate of 11%. Temporal lobectomy is an extremely effective therapy for seizures originating there-however, surgical intervention must be weighed against its morbidity and mortality outcomes.

Complications, Readmissions, and Revisions for Spine Procedures Performed by Orthopedic Surgeons Versus Neurosurgeons: A Retrospective, Longitudinal Study.

STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To examine the impact of training pathway, either neurosurgical or orthopedic, on complications, readmissions, and revisions in spine surgery. SUMMARY OF BACKGROUND DATA: Training pathway has been shown to have an impact on outcomes in various surgical subspecialties. Although training pathway has not been shown to have a significant impact on spine surgery outcomes in the perioperative period, long-term results are unknown. MATERIALS AND METHODS: A retrospective analysis of 197,682 patients receiving 1 of 3 common spine surgeries [lumbar laminectomy, lumbar fusion, and anterior cervical discectomy and fusion (ACDF)] between 2006 and 2010 was conducted. Patient data were obtained from a large claims database. Postoperative adverse effects, all-cause readmission, revision surgery rates, and intermediary payments in these cohorts of patients were compared between spine surgeons with either neurosurgical or orthopedic backgrounds. RESULTS: Patient demographics, hospital-stay characteristics, and medical comorbidities were similar between neurosurgeons and orthopedic surgeons. The risks of surgical complications, all-cause readmission, and revision surgery were also similar between neurosurgeons and orthopedic surgeons across all procedure types assessed, with several minor exceptions: neurosurgeons had marginally higher odds of any complication for lumbar fusions [odds ratio (OR) 1.14; 95% confidence interval (CI), 1.09-1.20] and ACDFs (OR, 1.09; 95% CI, 1.04-1.15). Neurosurgeons also had slightly higher rates of revision surgery for concurrent lumbar laminectomy with fusion (OR, 1.14; 95% CI, 1.08-1.22), and ACDFs (OR, 1.20; 95% CI, 1.14-1.28). No associations between surgeon type and any particular complication were consistently observed for all procedure groups. There were also no associations between surgeon type and 30-day all-cause readmission. Median total intermediary payments were somewhat higher for neurosurgery patients for all procedure groups assessed. CONCLUSIONS: Few significant associations between surgeon type and patient outcomes exist in the context of spine surgery. Those which do are small and unlikely to be clinically meaningful. LEVEL OF EVIDENCE: Level 3.

Relationship of A1 segment hypoplasia to anterior communicating artery aneurysm morphology and risk factors for aneurysm formation.

OBJECTIVE Hypoplasia of the A1 segment of the anterior cerebral artery is frequently observed in patients with anterior communicating artery (ACoA) aneurysms. The effect of this anatomical variant on ACoA aneurysm morphology is not well understood. METHODS Digital subtraction angiography images were reviewed for 204 patients presenting to the authors' institution with either a ruptured or an unruptured ACoA aneurysm. The ratio of the width of the larger A1 segment to the smaller A1 segment was calculated. Patients with an A1 ratio greater than 2 were categorized as having A1 segment hypoplasia. The relationship of A1 segment hypoplasia to both patient and aneurysm characteristics was then assessed. RESULTS Of 204 patients that presented with an ACoA aneurysm, 34 (16.7%) were found to have a hypoplastic A1. Patients with A1 segment hypoplasia were less likely to have a history of smoking (44.1% vs 62.9%, p = 0.0410). ACoA aneurysms occurring in the setting of a hypoplastic A1 were also found to have a larger maximum diameter (mean 7.7 vs 6.0 mm, p = 0.0084). When considered as a continuous variable, increasing A1 ratio was associated with decreasing aneurysm dome-to-neck ratio (p = 0.0289). There was no significant difference in the prevalence of A1 segment hypoplasia between ruptured and unruptured aneurysms (18.9% vs 10.7%; p = 0.1605). CONCLUSIONS Our results suggest that a hypoplastic A1 may affect the morphology of ACoA aneurysms. In addition, the relative lack of traditional risk factors for aneurysm formation in patients with A1 segment hypoplasia argues for the importance of hemodynamic factors in the formation of ACoA aneurysms in this anatomical setting.

Minimally Invasive Surgery Versus Open Surgery Spinal Fusion for Spondylolisthesis: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Compare minimally invasive surgery (MIS) and open surgery (OS) spinal fusion outcomes for the treatment of spondylolisthesis. SUMMARY OF BACKGROUND DATA: OS spinal fusion is an interventional option for patients with spinal disease who have failed conservative therapy. During the past decade, MIS approaches have increasingly been used, with potential benefits of reduced surgical trauma, postoperative pain, and length of hospital stay. However, current literature consists of single-center, low-quality studies with no review of approaches specific to spondylolisthesis only. METHODS: This first systematic review of the literature regarding MIS and OS spinal fusion for spondylolisthesis treatment was performed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for article identification, screening, eligibility, and inclusion. Electronic literature search of Medline/PubMed, Cochrane, EMBASE, and Scopus databases yielded 2489 articles. These articles were screened against established criteria for inclusion into this study. RESULTS: A total of five retrospective and five prospective articles with a total of 602 patients were found. Reported spondylolisthesis grades were I and II only. Overall, MIS was associated with less intraoperative blood loss (mean difference [MD], -331.04 mL; 95% confidence interval [CI], -490.48 to -171.59; P < 0.0001) and shorter length of hospital stay (MD, -1.74 days; 95% CI, -3.04 to -0.45; P = 0.008). There was no significant difference overall between MIS and OS in terms of functional or pain outcomes. Subgroup analysis of prospective studies revealed MIS had greater operative time (MD, 19.00 minutes; 95% CI, 0.90 to 37.10; P = 0.04) and lower final functional scores (weighted MD, -1.84; 95% CI, -3.61 to -0.07; P = 0.04) compared with OS. CONCLUSION: Current data suggests spinal fusion by MIS is a safe and effective approach to treat grade I and grade II spondylolisthesis. Moreover, although prospective trials associate MIS with better functional outcomes, longer-term and randomized trials are warranted to validate any association found in this study. LEVEL OF EVIDENCE: 2.

Hospital transfer associated with increased mortality after endovascular revascularization for acute ischemic stroke.

BACKGROUND: Patients with an acute ischemic stroke (AIS) due to large vessel occlusion often require transfer to an endovascular center for treatment. OBJECTIVE: To assess the effect of hospital transfer on outcomes after endovascular revascularization. METHODS: Outcomes of endovascular revascularization were compared between directly admitted and transferred patients using data from a national database and our own institution. RESULTS: 118 institutions within the database reported outcomes of 8533 inpatient admissions for endovascular treatment of AIS. Mortality rate (14.9% vs 18.6%; p=0.049) and mortality index (1.1 vs 1.6; p=0.048) were significantly lower among directly admitted patients than among transferred patients. Within our institutional cohort of 140 patients who underwent endovascular therapy, directly admitted patients had a significantly faster time to revascularization than transferred patients (277.4 vs 420.4 min; p≤0.0001). Among transferred patients, an increasing distance of transferred hospital to our home institution was associated with an increasing risk of mortality (unit OR=1.26, 95% CI 1.07 to 1.54; p=0.0061). CONCLUSIONS: Outcomes of revascularization may improve with methods to identify patients with large vessel occlusion before hospital admission, thus increasing the likelihood of initial triage to a comprehensive stroke center for patients eligible for endovascular intervention.

Quantitative analysis of the effect of institutional case volume on complications after surgical clipping of unruptured aneurysms.

OBJECTIVE The mechanism by which greater institutional case volume translates into improved outcomes after surgical clipping of unruptured intracranial aneurysms (UIAs) is not well established. The authors thus aimed to assess the effect of case volume on the rate of various types of complications after clipping of UIAs. METHODS Using information on the outcomes of inpatient admissions for surgical clipping of UIAs collected within a national database, the relationship of institutional case volume to the incidence of different types of complications after clipping was investigated. Complications were subdivided into different categories, which included all complications, ischemic stroke, intracerebral hemorrhage, medical complications, infectious complications, complications related to anesthesia, and wound complications. The relationship of case volume to different types of complications was assessed using linear regression analysis. The relationships between case volume and overall complication and stroke rates were fit with both linear and quadratic equations. The numerical cutoff for institutional case volume above and below which the authors found the greatest differences in mean overall complication and stroke rate was determined using classification and regression tree (CART) analysis. RESULTS Between October 2012 and September 2015, 125 health care institutions reported patient outcomes from a total of 6040 cases of clipping of UIAs. On linear regression analysis, increasing case volume was negatively correlated to both overall complications (r2 = 0.046, p = 0.0234) and stroke (r2 = 0.029, p = 0.0557) rate, although the relationship of case volume to the complication (r2 = 0.092) and stroke (r2 = 0.067) rate was better fit with a quadratic equation. On CART analysis, the cutoff for the case number that yielded the greatest difference in overall complications and stroke rate between higher- or lower-volume centers was 6 cases/year and 3 cases/year, respectively. CONCLUSIONS Although the authors confirm that increasing case volume is associated with reduced complications after clipping of UIAs, their results suggest that the relationship between case volume and complications is not necessarily linear. Moreover, these results indicate that the effect of case volume on outcome is most evident between very-low-volume centers relative to centers with a medium-to-high volume.

Comprehensive biomechanical analysis of three reconstruction techniques following total sacrectomy: an in vitro human cadaveric model.

OBJECTIVE Aggressive sacral tumors often require en bloc resection and lumbopelvic reconstruction. Instrumentation failure and pseudarthrosis remain a clinical concern to be addressed. The objective in this study was to compare the biomechanical stability of 3 distinct techniques for sacral reconstruction in vitro. METHODS In a human cadaveric model study, 8 intact human lumbopelvic specimens (L2-pelvis) were tested for flexion-extension range of motion (ROM), lateral bending, and axial rotation with a custom-designed 6-df spine simulator as well as axial compression stiffness with the MTS 858 Bionix Test System. Biomechanical testing followed this sequence: 1) intact spine; 2) sacrectomy (no testing); 3) Model 1 (L3-5 transpedicular instrumentation plus spinal rods anchored to iliac screws); 4) Model 2 (addition of transiliac rod); and 5) Model 3 (removal of transiliac rod; addition of 2 spinal rods and 2 S-2 screws). Range of motion was measured at L4-5, L5-S1/cross-link, L5-right ilium, and L5-left ilium. RESULTS Flexion-extension ROM of the intact specimen at L4-5 (6.34° ± 2.57°) was significantly greater than in Model 1 (1.54° ± 0.94°), Model 2 (1.51° ± 1.01°), and Model 3 (0.72° ± 0.62°) (p < 0.001). Flexion-extension at both the L5-right ilium (2.95° ± 1.27°) and the L5-left ilium (2.87° ± 1.40°) for Model 3 was significantly less than the other 3 cohorts at the same level (p = 0.005 and p = 0.012, respectively). Compared with the intact condition, all 3 reconstruction groups statistically significantly decreased lateral bending ROM at all measured points. Axial rotation ROM at L4-5 for Model 1 (2.01° ± 1.39°), Model 2 (2.00° ± 1.52°), and Model 3 (1.15° ± 0.80°) was significantly lower than the intact condition (5.02° ± 2.90°) (p < 0.001). Moreover, axial rotation for the intact condition and Model 3 at L5-right ilium (2.64° ± 1.36° and 2.93° ± 1.68°, respectively) and L5-left ilium (2.58° ± 1.43° and 2.93° ± 1.71°, respectively) was significantly lower than for Model 1 and Model 2 at L5-right ilium (5.14° ± 2.48° and 4.95° ± 2.45°, respectively) (p = 0.036) and L5-left ilium (5.19° ± 2.34° and 4.99° ± 2.31°) (p = 0.022). Last, results of the axial compression testing at all measured points were not statistically different among reconstructions. CONCLUSIONS The addition of a transverse bar in Model 2 offered no biomechanical advantage. Although the implementation of 4 iliac screws and 4 rods conferred a definitive kinematic advantage in Model 3, that model was associated with significantly restricted lumbopelvic ROM.

Discharge to a rehabilitation facility is associated with decreased 30-day readmission in elective spinal surgery.

The aim of our study was to determine independent predictors of discharge disposition to rehabilitation or skilled care (SC) facilities and investigate whether discharge location is associated with unplanned readmission and/or reoperation rates. All elective spinal surgery patients in a national surgical registry were analyzed using between 2011 and 2012. Multivariable logistic regression analysis was used to assess for predictors of discharge to rehabilitation or SC facilities versus home as well as to determine whether discharge disposition was significantly associated with the 30-day unplanned readmission or reoperation. Of 34,023 elective spinal surgery patients, the distribution of discharge locations was as follows: 30,606 (90.0%) discharged home, 1674 (4.9%) discharged to rehabilitation, and 1743 (5.1%) discharged to SC. Patients discharged home were associated with the lowest complication rate relative to rehabilitation and SC facilities. Following multivariable regression analysis, there was a significant increase in the odds of discharge to rehabilitation associated with age, male gender, current smoking, ASA class three and four, history of diabetes, operative time, total hospital length of stay, preoperative neurologic morbidity and having at least one postoperative morbidity event. Moreover, there were 804 (4.06%) 30-day unplanned readmissions and 822 (2.45%) unplanned reoperations. After risk adjustment, discharge to rehabilitation was independently associated with decreased odds of 30-day unplanned readmission (OR=0.41; p=0.008) but not reoperation.