Does type of bone graft matter? A retrospective review of the use of biological bone grafts in patients undergoing elective 1-3 level spinal interbody fusion.

OBJECTIVE: There is a lack of strong evidence for use of expensive bone substitutes. This study compares perioperative data and patient reported quality-of-life outcomes across the varied types of bone graft extenders. The study analyzes the existing Quality and Outcomes Database and evaluates patient reported outcomes for 1-3 level lumbar fusion procedures comparing across different types of biologics bone graft. METHODS: We retrospectively analyzed a prospectively collected data registry. Bone graft implant data were collected and grouped into the following categories: (1) Autograft with basic allograft (2) Enhanced, synthetic, or cellular allograft (3) Use of BMP. Preoperative and 1 year patient reported outcomes and perioperative data from the prospective collected registry were analyzed. RESULTS: There were 384 patients included in this study. There were 168 (43.8%) patients in group 1, 133 (34.6%) patients in group 2, and 83 (21.6%) in group 3. There were no group differences in baseline or 1 year back pain, leg pain, ODI, or EQ-5D. The GLM Repeated Measures results indicate a significant difference within each of the three groups between the preoperative and postoperative measures for back pain, leg pain, ODI, and EQ-5D. The change over time was not significantly different between the groups. CONCLUSIONS: Bone graft extenders are a significant contributor to the cost of lumbar fusion. This study demonstrates no difference in preoperative, and 1 year patient reported outcomes between the three groups. There was no significant difference in rate of reoperations across the three groups.

Does diabetes affect outcome or reoperation rate after lumbar decompression or arthrodesis? A matched analysis of the Quality Outcomes Database data set.

OBJECTIVE: Diabetes mellitus (DM) is a known risk factor for postsurgical and systemic complications after lumbar spinal surgery. Smaller studies have also demonstrated diminished improvements in patient-reported outcomes (PROs), with increased reoperation and readmission rates after lumbar surgery in patients with DM. The authors aimed to examine longer-term PROs in patients with DM undergoing lumbar decompression and/or arthrodesis for degenerative pathology. METHODS: The Quality Outcomes Database was queried for patients undergoing elective lumbar decompression and/or arthrodesis for degenerative pathology. Patients were grouped into DM and non-DM groups and optimally matched in a 1:1 ratio on 31 baseline variables, including the number of operated levels. Outcomes of interest were readmissions and reoperations at 30 and 90 days after surgery in addition to improvements in Oswestry Disability Index, back pain, and leg pain scores and quality-adjusted life-years at 90 days after surgery. RESULTS: The matched decompression cohort comprised 7836 patients (3236 [41.3] females) with a mean age of 63.5 ± 12.6 years, and the matched arthrodesis cohort comprised 7336 patients (3907 [53.3%] females) with a mean age of 64.8 ± 10.3 years. In patients undergoing lumbar decompression, no significant differences in nonroutine discharge, length of stay (LOS), readmissions, reoperations, and PROs were observed. In patients undergoing lumbar arthrodesis, nonroutine discharge (15.7% vs 13.4%, p < 0.01), LOS (3.2 ± 2.0 vs 3.0 ± 3.5 days, p < 0.01), 30-day (6.5% vs 4.4%, p < 0.01) and 90-day (9.1% vs 7.0%, p < 0.01) readmission rates, and the 90-day reoperation rate (4.3% vs 3.2%, p = 0.01) were all significantly higher in the DM group. For DM patients undergoing lumbar arthrodesis, subgroup analyses demonstrated a significantly higher risk of poor surgical outcomes with the open approach. CONCLUSIONS: Patients with and without DM undergoing lumbar spinal decompression alone have comparable readmission and reoperation rates, while those undergoing arthrodesis procedures have a higher risk of poor surgical outcomes up to 90 days after surgery. Surgeons should target optimal DM control preoperatively, particularly for patients undergoing elective lumbar arthrodesis.

Microendoscopic Posterior Cervical Laminoforaminotomy for C4 Radiculopathy.

OBJECTIVE: Cervical microendoscopic laminoforaminotomy (MELF) has been proven to be an effective, motion preserving procedure for the surgical treatment of cervical radiculopathy. Cervical 4 (C4) radiculopathies are often unrecognized by the initial evaluating physician and may be misdiagnosed as axial neck pain. In this study, we compare MELF to anterior cervical disk fusion (ACDF) for C4 radiculopathy in the largest series of minimally invasive foraminotomy for C4 radiculopathy to date. METHODS: This is a single-institution retrospective chart review of 42 cases for C4 radiculopathy, 21 MELF and 21 ACDF. Primary outcome measures were length of surgery, length of hospital stay, and time to return to work. Secondary outcome measures were visual analog scale (VAS) neck pain and reoperation rate. RESULTS: All patients were diagnosed with a unilateral C4 radiculopathy using magnetic resonance imaging or steroid injections. The length of surgery and length of hospital stay were significantly decreased in the MELF group compared with ACDF. VAS neck pain significantly decreased for patients in both groups, but the difference between MELF and ACDF was not statistically significant. There were no major complications. No patient underwent revision at the index level or adjacent levels in the MELF group. CONCLUSIONS: We demonstrate that C4 radiculopathy can be identified with appropriate history, physical examination, and targeted nerve root injections. When identified, these radiculopathies that fail conservative therapy can be effectively treated with cervical microendoscopic laminoforaminotomy, with comparable outcomes to ACDF. The length of surgery and length of stay are reduced when compared with ACDF.

Research using the Quality Outcomes Database: accomplishments and future steps toward higher-quality real-world evidence.

OBJECTIVE: The Quality Outcomes Database (QOD) was established in 2012 by the NeuroPoint Alliance, a nonprofit organization supported by the American Association of Neurological Surgeons. Currently, the QOD has launched six different modules to cover a broad spectrum of neurosurgical practice-namely lumbar spine surgery, cervical spine surgery, brain tumor, stereotactic radiosurgery (SRS), functional neurosurgery for Parkinson's disease, and cerebrovascular surgery. This investigation aims to summarize research efforts and evidence yielded through QOD research endeavors. METHODS: The authors identified all publications from January 1, 2012, to February 18, 2023, that were produced by using data collected prospectively in a QOD module without a prespecified research purpose in the context of quality surveillance and improvement. Citations were compiled and presented along with comprehensive documentation of the main study objective and take-home message. RESULTS: A total of 94 studies have been produced through QOD efforts during the past decade. QOD-derived literature has been predominantly dedicated to spinal surgical outcomes, with 59 and 22 studies focusing on lumbar and cervical spine surgery, respectively, and 6 studies focusing on both. More specifically, the QOD Study Group-a research collaborative between 16 high-enrolling sites-has yielded 24 studies on lumbar grade 1 spondylolisthesis and 13 studies on cervical spondylotic myelopathy, using two focused data sets with high data accuracy and long-term follow-up. The more recent neuro-oncological QOD efforts, i.e., the Tumor QOD and the SRS Quality Registry, have contributed 5 studies, providing insights into the real-world neuro-oncological practice and the role of patient-reported outcomes. CONCLUSIONS: Prospective quality registries are an important resource for observational research, yielding clinical evidence to guide decision-making across neurosurgical subspecialties. Future directions of the QOD efforts include the development of research efforts within the neuro-oncological registries and the American Spine Registry-which has now replaced the inactive spinal modules of the QOD-and the focused research on high-grade lumbar spondylolisthesis and cervical radiculopathy.

Feasibility and Safety of Microendoscopic Posterior Cervical Foraminotomy in an Ambulatory Surgery Center: A Longitudinal Experience with 1000 Cases.

OBJECTIVE: Ambulatory surgery centers (ASCs) have become an increasingly attractive setting for spine surgery in recent decades. Although posterior cervical foraminotomy (PCF) is widely performed in ASCs, there are no studies supporting the safety of this practice. We aimed to demonstrate the feasibility and safety of microendoscopic (MED)-PCF in a large cohort of patients at a freestanding ASC. METHODS: Consecutive patients undergoing MED-PCF for unilateral cervical radiculopathy at a single freestanding ASC from January 2013 to December 2020 were queried. Standard demographic and perioperative data were collected. Outcomes included need for inpatient transfer, perioperative complications, 30-day readmission, 30-day reoperation, and clinical improvement according to the Odom criteria. RESULTS: A total of 1106 patients underwent MED-PCF during the study period. Mean age was 53.3 ± 10.3 years. Most patients underwent decompression at C5-6 (31.4%) or C6-7 (51.9%). Approximately 10% underwent surgery at multiple levels. Mean operative time was 40.0 ± 16.4 minutes. There were no intraoperative or immediate postoperative complications. All patients were discharged home within a few hours of surgery. The rates of 30-day readmission (0.81%) and reoperation (0.36%) were exceedingly low. Nearly 3 quarters of patients (73.7%) achieved a good or excellent clinical outcome (73.7%) according to the Odom criteria. CONCLUSIONS: MED-PCF can be performed in a freestanding ASC with exceedingly low rates of perioperative complications and short-term readmission or reoperation. Our findings support the ongoing migration of PCF from the hospital to the ambulatory setting. Future studies assessing patient-reported outcomes and long-term reoperation rates are necessary.

Outpatient versus inpatient lumbar decompression surgery: a matched noninferiority study investigating clinical and patient-reported outcomes.

OBJECTIVE: Spine surgery represents an ideal target for healthcare cost reduction efforts, with outpatient surgery resulting in significant cost savings. With an increased focus on value-based healthcare delivery, lumbar decompression surgery has been increasingly performed in the outpatient setting when appropriate. The aim of this study was to compare clinical and patient-reported outcomes following outpatient and inpatient lumbar decompression surgery. METHODS: The Quality Outcomes Database (QOD) was queried for patients undergoing elective one- or two-level lumbar decompression (laminectomy or laminotomy with or without discectomy) for degenerative spine disease. Patients were grouped as outpatient if they had a length of stay (LOS) < 24 hours and as inpatient if they stayed in the hospital ≥ 24 hours. Patients with ≥ 72-hour stay were excluded from the comparative analysis to increase baseline comparability between the two groups. To create two highly homogeneous groups, optimal matching was performed at a 1:1 ratio between the two groups on 38 baseline variables, including demographics, comorbidities, symptoms, patient-reported scores, indications, and operative details. Outcomes of interest were readmissions and reoperations at 30 days and 3 months after surgery, overall satisfaction, and decrease in Oswestry Disability Index (ODI), back pain, and leg pain at 3 months after surgery. Satisfaction was defined as a score of 1 or 2 in the North American Spine Society patient satisfaction index. Noninferiority of outpatient compared with inpatient surgery was defined as risk difference of < 1.5% at a one-sided 97.5% confidence interval. RESULTS: A total of 18,689 eligible one- and two-level decompression surgeries were identified. The matched study cohorts consisted of 5016 patients in each group. Nonroutine discharge was slightly less common in the outpatient group (0.6% vs 0.3%, p = 0.01). The 30-day readmission rates were 4.4% and 4.3% for the outpatient and inpatient groups, respectively, while the 30-day reoperation rates were 1.4% and 1.5%. The 3-month readmission rates were 6.3% for both groups, and the 3-month reoperation rates were 3.1% for the outpatient cases and 2.9% for the inpatient cases. Overall satisfaction at 3 months was 88.8% for the outpatient group and 88.4% for the inpatient group. Noninferiority of outpatient surgery was documented for readmissions, reoperations, and patient-reported satisfaction from surgery. CONCLUSIONS: Outpatient lumbar decompression surgery demonstrated slightly lower nonroutine discharge rates in comparison with inpatient surgery. Noninferiority in clinical outcomes at 30 days and 3 months after surgery was documented for outpatient compared with inpatient decompression surgery. Additionally, outpatient decompression surgery performed noninferiorly to inpatient surgery in achieving patient satisfaction from surgery.

Minimally invasive versus open lumbar spinal fusion: a matched study investigating patient-reported and surgical outcomes.

OBJECTIVE: With the expanding indications for and increasing popularity of minimally invasive surgery (MIS) for lumbar spinal fusion, large-scale outcomes analysis to compare MIS approaches with open procedures is warranted. METHODS: The authors queried the Quality Outcomes Database for patients who underwent elective lumbar fusion for degenerative spine disease. They performed optimal matching, at a 1:2 ratio between patients who underwent MIS and those who underwent open lumbar fusion, to create two highly homogeneous groups in terms of 33 baseline variables (including demographic characteristics, comorbidities, symptoms, patient-reported scores, indications, and operative details). The outcomes of interest were overall satisfaction, decrease in Oswestry Disability Index (ODI), and back and leg pain, as well as hospital length of stay (LOS), operative time, reoperations, and incidental durotomy rate. Satisfaction was defined as a score of 1 or 2 on the North American Spine Society scale. Minimal clinically important difference (MCID) in ODI was defined as ≥ 30% decrease from baseline. Outcomes were assessed at the 3- and 12-month follow-up evaluations. RESULTS: After the groups were matched, the MIS and open groups consisted of 1483 and 2966 patients, respectively. Patients who underwent MIS fusion had higher odds of satisfaction at 3 months (OR 1.4, p = 0.004); no difference was demonstrated at 12 months (OR 1.04, p = 0.67). Lumbar stenosis, single-level fusion, higher American Society of Anesthesiologists Physical Status Classification System grade, and absence of spondylolisthesis were most prominently associated with higher odds of satisfaction with MIS compared with open surgery. Patients in the MIS group had slightly lower ODI scores at 3 months (mean difference 1.61, p = 0.006; MCID OR 1.14, p = 0.0495) and 12 months (mean difference 2.35, p < 0.001; MCID OR 1.29, p < 0.001). MIS was also associated with a greater decrease in leg and back pain at both follow-up time points. The two groups did not differ in operative time and incidental durotomy rate; however, LOS was shorter for the MIS group. Revision surgery at 12 months was less likely for patients who underwent MIS (4.1% vs 5.6%, p = 0.032). CONCLUSIONS: In patients who underwent lumbar fusion for degenerative spinal disease, MIS was associated with higher odds of satisfaction at 3 months postoperatively. No difference was demonstrated at the 12-month follow-up. MIS maintained a small, yet consistent, superiority in decreasing ODI and back and leg pain, and MIS was associated with a lower reoperation rate.

Bilateral Decompressive Hemicraniectomy for Diffuse Cerebral Edema and Medically Refractory Elevated Intracranial Pressure in Aneurysmal Subarachnoid Hemorrhage: A Case Series.

Decompressive hemicraniectomy (DCHC) may be indicated in the setting of subarachnoid hemorrhage (SAH) complicated by persistent elevated intracranial pressure (ICP) that is refractory to medical interventions. Outcomes can be variable as indications for surgery can include focal hematomas, infarctions, and regional or diffuse edema. Bilateral DCHC for medically refractory elevated ICP in the setting of SAH is not well described in the literature, and the viability of this option in terms of patient outcomes is unclear. We describe the cases of four patients with medically refractory ICP secondary to diffuse cerebral edema who underwent bilateral DCHC in the setting of SAH. This is a retrospective case review of four patients with aneurysmal SAH who underwent bilateral DCHC for management of diffuse global edema resulting in medically refractory ICP. We describe two patients who made impressive recoveries after bilateral DCHC and two patients who required significant continued care needs despite ICP control in all patients. Bilateral DCHC is a viable option for control of refractory elevated ICP in SAH patients who develop diffuse cerebral edema. Bilateral DCHC in this setting can be considered after exhaustion of other therapeutic options.

Preoperative Acetazolamide Challenge in Pediatric Chiari I Malformation.

PURPOSE: In patients who present with headaches and Chiari 1 malformation without cranial nerve or brainstem dysfunction or syrinx formation, the decision to decompress can be difficult to make. We present a case series examining the use of acetazolamide as a diagnostic aid to determine candidacy for decompression. METHODS: A single pediatric neurosurgeon's (M.M.H.) experience from 2003 to 2018 was retrospectively reviewed. All cases evaluated in the clinic for CPT code of Chiari 1 malformation were analyzed. Inclusion criteria were patients with diagnosis of Chiari 1 malformation and headache-predominant symptoms who underwent an acetazolamide challenge test. Exclusion criteria included age over 18, syrinx, or significant clinical evidence of brainstem compression or cranial nerve dysfunction. Data were recorded with respect to response to acetazolamide. Surgical outcomes were assessed using the Chicago Chiari Outcome Scale (CCOS) pain category and the improve/same/worse (IWS) scale. Overall satisfaction from surgery was also recorded. RESULTS: Forty-five patients met inclusion criteria and underwent acetazolamide challenge. Thirty-three (73.3%) patients showed improvement of their symptoms with acetazolamide challenge (responders). Of the 33 responders, 25 (75.8%) underwent Chiari decompression. The remaining 8 (24.2%) responders experienced persistent improvement of their symptoms after the acetazolamide trial and did not require intervention. Twelve (26.7%) patients did not improve with acetazolamide (nonresponders) of which 11 (91.7% of nonreponders) never required intervention. One nonresponder eventually underwent Chiari decompression due to progressively worsening and debilitating headaches. All twenty-five (100%) responders improved after surgery and 24 (96%) were satisfied with the outcome of surgery. The average responder CCOS pain score was 3.52 out of 4. The nonresponder who did not improve with acetazolamide had persistent severe headaches after decompression. The CCOS pain score for this nonresponder was 2 out of 4. CONCLUSION: Pediatric headache-predominant Chiari 1 malformation presents a difficult diagnostic dilemma. The authors describe a trial of acetazolamide as a preoperative diagnostic tool to aid the decision to decompress. Further studies will need to be performed to determine the effectiveness of preoperative acetazolamide in identifying which patients may benefit from surgical decompression.

Reversible cerebral vasoconstriction syndrome successfully treated by intrathecal nicardipine.

Reversible cerebral vasoconstriction syndrome (RCVS) presents with a thunderclap headache, often prompting brain imaging. Most patients fully recover with supportive care and time, but oral calcium channel blockers are often used in patients with severe vasoconstriction. In this case report, we present a patient with severe vasoconstriction leading to weakness refractory to oral calcium channel blockers. Intrathecal nicardipine was administered via an external ventricular drain and the patient subsequently showed improvement of her weakness and significant improvement of vasospasm on Computed Tomography Angiography. We suggest further studies to determine the efficacy of intrathecal nicardipine in patients with RCVS not responsive to oral calcium channel blockers.

1-Year Mortality and Surgery Incidence in Older US Adults with Cervical Spine Fracture.

BACKGROUND: Traumatic cervical spinal cord injuries (SCIs) can be lethal and are especially dangerous for older adults. Falls from standing and risk factors for a cervical fracture and spinal cord injury increase with age. This study estimates the 1-year mortality for patients with a cervical fracture and resultant SCI and compares the mortality rate with that from an isolated cervical fracture. METHODS: We performed a retrospective cohort study of U.S. Medicare patients older than 65 years of age. International Classification of Diseases (ICD)-9 codes were used to identify patients with a cervical fracture without SCI and patients with a cervical fracture with SCI between 2007 and 2014. Our primary outcome was 1-year mortality cumulative incidence rate; our secondary outcome was the cumulative incidence rate of surgical intervention. Propensity weighted analysis was performed to balance covariates between the groups. RESULTS: The SCI cohort had a 1-year mortality of 36.5%, compared with 31.1% in patients with an isolated cervical fracture (risk difference 5.4% (2.9%-7.9%)). Patients with an SCI were also more likely to undergo surgical intervention compared with those without a SCI (23.1% and 10.3%, respectively; risk difference 12.8% (10.8%-14.9%)). CONCLUSIONS: Using well-adjusted population-level data in older adults, this study estimates the 1-year mortality after SCI in older adults to be 36.5%. The mortality after a cervical fracture with SCI was 5 percentage points higher than in patients without SCI, and this difference is smaller than one might expect, likely representing the frailty of this population and unmeasured covariates.

Author Correction: Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been established. We show that, to our surprise, suppression of KRAS increased autophagic flux, as did pharmacological inhibition of its effector ERK MAPK. Furthermore, we demonstrate that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. We speculated that ERK inhibition might thus enhance PDAC dependence on autophagy, in part by impairing other KRAS- or ERK-driven metabolic processes. Accordingly, we found that the autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specific autophagy regulators synergistically enhanced the ability of ERK inhibitors to mediate antitumor activity in KRAS-driven PDAC. We conclude that combinations of pharmacologic inhibitors that concurrently block both ERK MAPK and autophagic processes that are upregulated in response to ERK inhibition may be effective treatments for PDAC.

KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers with a dismal 7% 5-year survival rate and is projected to become the second leading cause of cancer-related deaths by 2020. KRAS is mutated in 95% of PDACs and is a well-validated driver of PDAC growth and maintenance. However, despite comprehensive efforts, an effective anti-RAS drug has yet to reach the clinic. Different paths to inhibiting RAS signaling are currently under investigation in the hope of finding a successful treatment. Recently, direct RAS binding molecules have been discovered, challenging the perception that RAS is an "undruggable" protein. Other strategies currently being pursued take an indirect approach, targeting proteins that facilitate RAS membrane association or downstream effector signaling. Unbiased genetic screens have identified synthetic lethal interactors of mutant RAS. Most recently, metabolic targets in pathways related to glycolytic signaling, glutamine utilization, autophagy, and macropinocytosis are also being explored. Harnessing the patient's immune system to fight their cancer is an additional exciting route that is being considered. The "best" path to inhibiting KRAS has yet to be determined, with each having promise as well as potential pitfalls. We will summarize the state-of-the-art for each direction, focusing on efforts directed toward the development of therapeutics for pancreatic cancer patients with mutated KRAS.