What facets of physical function are most important to adults diagnosed with cancer?

PURPOSE: Successful patient-focused drug development involves selecting and measuring outcomes in clinical trials that are important to patients. The U.S. Food & Drug Administration's definition of clinical benefit includes how patients feel, function, or survive. Patients are considered the experts in describing how they feel and function. In cancer trials, patient-reported measures of physical function provide insight into how patients function at baseline, benefit from the interventions being studied, and the impact of treatment side effects. We conducted a qualitative study with adults diagnosed with cancer to describe facets of physical function from their perspective and to identify which facets are most important to this patient population. METHODS: Using concept elicitation and cognitive interviewing techniques, we conducted semi-structured interviews with 72 adults ≥ 22 years of age with cancer who received treatment with an anticancer drug or biologic within six months of the interview. We selected participants using purposive sampling with the aim to elicit diverse experiences regarding how they may interpret and respond to questions related to physical function. Participants were presented with patient-reported outcome (PRO) items representative of PRO measures used in cancer and general populations. RESULTS: Five facets of how physical function relates to activities were defined from the patient perspective: ability, difficulty, limitation, satisfaction, and completion. More than half of the participants indicated that ability was the most important facet of physical function. The next most important were satisfaction (18.3%), limitation (14.1%), difficulty (5.6%), and completion (2.8%). CONCLUSION: This study demonstrates that we must be more specific about the facets of physical function that we set out to assess when we use PRO measures to describe the patient experience. These results have implications for the specificity of physical function facets when measured in cancer clinical trials.

Computed Tomography Volumetry of Bone Cement: Retrospective Blinded Validation of Commercially Available Semi-automated Edge Detection Software.

OBJECTIVE: Cement volumes are increasingly linked to orthopedic oncology and neurosurgical outcomes (construct durability, adjacent fracture), but manual cement volumetry remains time prohibitive. The authors aim to report performance of PACS-integrated volumetric software specifically for barium-enhanced polymethylmethacrylate cement. METHODS: Institutional review board-approved single-institution retrospective review of patients from 2019-2022 undergoing kyphoplasty for pathological compression fractures with a quantitative cement infuser providing true cement volume. An operator blinded to true cement volumes retrospectively performed software-assisted volumetry on follow-up computed tomography scans. RESULTS: Included were 91 kyphoplasty levels in 56 patients: mean age, 62 years (range, 34-85 years), 73% female. True cement volume (available for 44 of 66 procedures) was mean 4.5 mL per level (range, 1.2-15.6 mL). Measured cement volume (available for all procedures) yielded a mean of 6.1 mL per level (range, 1.5-27.9 mL). For the 57 levels (39 patients) where both true and measured cement volumes were available, linear regression intercept and slope were 1.46 (95% CI = 0.97-1.95, P < 0.001) and 0.52 (CI = 0.47-0.57, P < 0.001), respectively, suggesting measured volume averaged 1.46 mL greater than true volume, with each additional milliliter of measured volume corresponding to approximately 0.52 mL of true volume. There was no significant difference in the relationship between estimated and actual cement volume in thoracic levels (intercept = -0.24, CI = -1.13 to 0.66, P = 0.61; slope = 0.03, CI = -0.14 to 0.19, P = 0.73) compared with lumbar levels. The goodness-of-fit of the regression model was strong (R2 = 0.81). Discrepancies ranged from 90% underestimation to 52% overestimation; average, 17% overestimation. CONCLUSIONS: Semi-automated volumetry maintained a strong correlation with true volumes across the thoracic and lumbar curvatures, overestimating cement volume by a mean of 17% or 1.46 mL.

High-Impact Chronic Pain Transition in Lumbar Surgery Recipients.

OBJECTIVE: High-impact chronic pain (HICP) is a term that characterizes the presence of a severe and troubling pain-related condition. To date, the prevalence of HICP in lumbar spine surgery recipients and their HICP transitions from before to after surgery are unexplored. The purpose was to define HICP prevalence, transition types, and outcomes in lumbar spine surgery recipients and to identify predictors of HICP outcomes. METHODS: In total, 43,536 lumbar surgery recipients were evaluated for HICP transition. Lumbar spine surgery recipients were categorized as having HICP preoperatively and at 3 months after surgery if they exhibited chronic and severe pain and at least one major activity limitation. Four HICP transition groups (Stable Low Pain, Transition from HICP, Transition to HICP, and Stable High Pain) were categorized and evaluated for outcomes. Multivariate multinomial modeling was used to predict HICP transition categorization. RESULTS: In this sample, 15.1% of individuals exhibited HICP preoperatively; this value declined to 5.1% at 3 months after surgery. Those with HICP at baseline and 3 months had more comorbidities and worse overall outcomes. Biological, psychological, and social factors predicted HICP transition or Stable High Pain; some of the strongest involved social factors of 2 or more to transition to HICP (OR = 1.43; 95% CI = 1.21-1.68), and baseline report of pain/disability (OR = 3.84; 95% CI = 3.20-4.61) and psychological comorbidity (OR = 1.78; 95% CI = 1.48-2.12) to Stable Stable High Pain. CONCLUSION: The percentage of individuals with HICP preoperatively (15.1%) was low, which further diminished over a 3-month period (5.1%). Postoperative HICP groups had higher levels of comorbidities and worse baseline outcomes scores. Transition to and maintenance of HICP status was predicted by biological, psychological, and social factors.

How dimensions can guide surgical planning and training: a systematic review of Kambin's triangle.

OBJECTIVE: The authors sought to analyze the current literature to determine dimensional trends across the lumbar levels of Kambin's triangle, clarify the role of imaging techniques for preoperative planning, and understand the effect of inclusion of the superior articular process (SAP). This compiled knowledge of the triangle is needed to perform successful procedures, reduce nerve root injuries, and help guide surgeons in training. METHODS: The authors performed a search of multiple databases using combinations of keywords: Kambin's triangle, size, measurement, safe triangle, and bony triangle. Articles were included if their main findings included measurement of Kambin's triangle. The PubMed, Scopus, Ovid, Cochrane, Embase, and Medline databases were systematically searched for English-language articles with no time frame restrictions through July 2022. RESULTS: Eight studies comprising 132 patients or cadavers were included in the study. The mean ± SD age was 66.69 ± 9.6 years, and 53% of patients were male. Overall, the size of Kambin's triangle increased in area moving down vertebral levels, with L5-S1 being the largest (133.59 ± 4.36 mm2). This trend followed a linear regression model when SAP was kept (p = 0.008) and removed (p = 0.003). There was also a considerable increase in the size of Kambin's triangle if the SAP was removed. CONCLUSIONS: Here, the authors have provided the first reported systematic review of the literature of Kambin's triangle, its measurements at each lumbar level, and key areas of debate related to the definition of the working safe zone. These findings indicate that CT is heavily utilized for imaging of the safe zone, the area of Kambin's triangle tends to increase caudally, and variation exists between patients. Future studies should focus on using advanced imaging techniques for preoperative planning and establishing guidelines for surgeons.

Scoping review on the state of racial disparities literature in the treatment of neurosurgical disease: a call for action.

OBJECTIVE: Racial disparities are ubiquitous across medicine in the US. This study aims to assess the evidence of racial disparities within neurosurgery and across its subspecialties, with a specific goal of quantifying the distribution of articles devoted to either identifying, understanding, or reducing disparities. METHODS: The authors searched the MEDLINE, EMBASE, and Scopus databases by using keywords to represent the concepts of neurosurgery, patients, racial disparities, and specific study types. Two independent reviewers screened the article titles and abstracts for relevance. A third reviewer resolved conflicts. Data were then extracted from the included articles and each article was categorized into one of three phases: identifying, understanding, or reducing disparities. This review was conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. RESULTS: Three hundred seventy-one studies published between 1985 and 2023 were included. The distribution of racial disparities literature was not equally spread among specialties, with spine representing approximately 48.3% of the literature, followed by tumor (22.1%) and general neurosurgery (12.9%). Most studies were dedicated to identifying racial disparities (83.6%). The proportion of literature devoted to understanding and reducing disparities was much lower (15.1% and 1.3%, respectively). Black patients were the most negatively impacted racial/ethnic group in the review (63.3%). The Hispanic or Latino ethnic group was the second most negatively impacted (25.1%). The following categories-other outcomes (28.0%), the offering of treatment (21.6%), complications (18.6%), and survival (16.7%)-represented the most frequently measured outcomes. CONCLUSIONS: Although strides have been taken to identify racial disparities within neurosurgery, fewer studies have focused on understanding and reducing these disparities. The tremendous rise of literature within this domain but the relative paucity of solutions necessitates the study of targeted interventions to provide equitable care for all patients undergoing neurosurgical treatment.

Systemic considerations for the surgical treatment of spinal metastatic disease: a scoping literature review.

Systemic assessment is a pillar in the neurological, oncological, mechanical, and systemic (NOMS) decision-making framework for the treatment of patients with spinal metastatic disease. Despite this importance, emerging evidence relating systemic considerations to clinical outcomes following surgery for spinal metastatic disease has not been comprehensively summarised. We aimed to conduct a scoping literature review of this broad topic. We searched MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL databases from Jan 1, 2000, to July 31, 2021. 61 articles were included, accounting for a total of 22 335 patients. Preoperative systemic variables negatively associated with postoperative clinical outcomes included demographics (eg, older age [>60 years], Black race, male sex, low or elevated body-mass index, and smoking status), medical comorbidities (eg, cardiac, pulmonary, hepatic, renal, endocrine, vascular, and rheumatological), biochemical abnormalities (eg, hypoalbuminaemia, atypical blood cell counts, and elevated C-reactive protein concentration), low muscle mass, generalised motor weakness (American Spinal Cord Injury Association Impairment Scale grade and Frankel grade) and poor ambulation, reduced performance status, and systemic disease burden. This is the first comprehensive scoping review to broadly summarise emerging evidence relevant to the systemic assessment component of the widely used NOMS framework for spinal metastatic disease decision making. Medical, surgical, and radiation oncologists can consider these findings when prognosticating spinal metastatic disease-related surgical outcomes on the basis of patients' systemic condition. These factors might inform a shared decision-making approach with patients and their families.

Juxtametallic Bipolar Bone Radiofrequency Ablation: Thermal Monitoring in an Ex-Vivo Model with Specimen MRI and Histopathologic Correlation.

PURPOSE: To measure the ablation zone temperature and nontarget tissue temperature during radiofrequency (RF) ablation in bone containing metal instrumentation versus no metal instrumentation (control group). MATERIALS AND METHODS: Ex vivo experiments were performed on 15 swine vertebrae (control, n = 5; titanium screw, n = 5; stainless steel screw, n = 5). Screws and RF ablation probe were inserted identically under fluoroscopy. During RF ablation (3 W, 5 minutes), temperature was measured 10 mm from RF ablation centerpoint and in muscle contacting the screw. Magnetic resonance (MR) imaging, gross pathologic, and histopathologic analyses were performed on 1 specimen from each group. RESULTS: Ablation zone temperatures at 2.5 and 5 minutes increased by 12.2 °C ± 2.6 °C and 21.5 °C ± 2.1 °C (control); 11.0 °C ± 4.1 °C and 20.0 °C ± 2.9 °C (juxta-titanium screw), and 10.0 °C ± 3.4 °C and 17.2 °C ± 3.5 °C (juxta-stainless steel) screw; differences among groups did not reach significance by analysis of variance (P = .87). Mixed-effects linear regression revealed a statistically significant increase in temperature over time in all 3 groups (4.2 °C/min ± 0.4 °C/min, P < .001). Compared with the control, there was no significant difference in the temperature change over time for titanium (-0.3 °C/min ± 0.5 °C/min, P = .53) or steel groups (-0.4 °C/min ± 0.5 °C/min, P = .38). The mean screw temperature at the final time point did not show a statistically significant change compared with baseline in either the titanium group (-1.2 °C ± 2.3 °C, P = .50) or steel group (2.6 °C ± 2.9 °C, P = .11). MR imaging and pathologic analyses revealed homogeneous ablation without sparing of the peri-hardware zones. CONCLUSIONS: Adjacent metallic instrumentation did not affect the rate of or absolute increase in temperature in the ablation zone, did not create peri-metallic ablation inhomogeneities, and did not result in significant nontarget heating of muscle tissue in contact with the metal instrumentation.

Management of unruptured incidentally found intracranial saccular aneurysms.

Unruptured intracranial saccular aneurysms occur in 3-5% of the general population. As the use of diagnostic medical imaging has steadily increased over the past few decades with the increased availability of computed tomography (CT) and magnetic resonance imaging (MRI), so has the detection of incidental aneurysms. The management of an unruptured intracranial saccular aneurysm is challenging for both patients and physicians, as the decision to intervene must weigh the risk of rupture and resultant subarachnoid hemorrhage against the risk inherent to the surgical or endovascular procedure. The purpose of this paper is to provide an overview of factors to be considered in the decision to offer treatment for unruptured intracranial aneurysms in adults. In addition, we review aneurysm and patient characteristics that favor surgical clipping over endovascular intervention and vice versa. Finally, the authors propose a novel, simple, and clinically relevant algorithm for observation versus intervention in unruptured intracranial aneurysms based on the PHASES scoring system.

Systematic review of charged-particle therapy for chordomas and sarcomas of the mobile spine and sacrum.

OBJECTIVE: Long-term local control in patients with primary chordoma and sarcoma of the spine and sacrum is increasingly reliant upon en bloc resection with negative margins. At many institutions, adjuvant radiation is recommended; definitive radiation is also recommended for the treatment of unresectable tumors. Because of the high off-target radiation toxicities associated with conventional radiotherapy, there has been growing interest in the use of proton and heavy-ion therapies. The aim of this study was to systematically review the literature regarding these therapies. METHODS: The PubMed, OVID, Embase, and Web of Science databases were queried for articles describing the use of proton, combined proton/photon, or heavy-ion therapies for adjuvant or definitive radiotherapy in patients with primary sarcoma or chordoma of the mobile spine and sacrum. A qualitative synthesis of the results was performed, focusing on overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS); local control; and postradiation toxicities. RESULTS: Of 595 unique articles, 64 underwent full-text screening and 38 were included in the final synthesis. All studies were level III or IV evidence with a high risk of bias; there was also significant overlap in the reported populations, with six centers accounting for roughly three-fourths of all reports. Five-year therapy outcomes were as follows: proton-only therapies, OS 67%-82%, PFS 31%-57%, and DFS 52%-62%; metastases occurred in 17%-18% and acute toxicities in 3%-100% of cases; combined proton/photon therapy, local control 62%-85%, OS 78%-87%, PFS 90%, and DFS 61%-72%; metastases occurred in 12%-14% and acute toxicities in 84%-100% of cases; and carbon ion therapy, local control 53%-100%, OS 52%-86%, PFS (only reported for 3 years) 48%-76%, and DFS 50%-53%; metastases occurred in 2%-39% and acute toxicities in 26%-48%. There were no studies directly comparing outcomes between photon and charged-particle therapies or comparing outcomes between radiation and surgical groups. CONCLUSIONS: The current evidence for charged-particle therapies in the management of sarcomas of the spine and sacrum is limited. Preliminary evidence suggests that with these therapies local control and OS at 5 years are comparable among various charged-particle options and may be similar between those treated with definitive charged-particle therapy and historical surgical cohorts. Further research directly comparing charged-particle and photon-based therapies is necessary.

Pseudarthrosis rate following anterior cervical discectomy with fusion using an allograft cellular bone matrix: a multi-institutional analysis.

OBJECTIVE: The use of osteobiologics, engineered materials designed to promote bone healing by enhancing bone growth, is becoming increasingly common for spinal fusion procedures, but the efficacy of some of these products is unclear. The authors performed a retrospective, multi-institutional study to investigate the clinical and radiographic characteristics of patients undergoing single-level anterior cervical discectomy with fusion performed using the osteobiologic agent Osteocel, an allograft mesenchymal stem cell matrix. METHODS: The medical records across 3 medical centers and 12 spine surgeons were retrospectively queried for patients undergoing single-level anterior cervical discectomy and fusion (ACDF) with the use of Osteocel. Pseudarthrosis was determined based on CT or radiographic imaging of the cervical spine. Patients were determined to have radiographic pseudarthrosis if they met any of the following criteria: 1) lack of bridging bone on CT obtained > 300 days postoperatively, 2) evidence of instrumentation failure, or 3) motion across the index level as seen on flexion-extension cervical spine radiographs. Univariate and multivariate analyses were then performed to identify independent preoperative or perioperative predictors of pseudarthrosis in this population. RESULTS: A total of 326 patients met the inclusion criteria; 43 (13.2%) patients met criteria for pseudarthrosis, of whom 15 (34.9%) underwent revision surgery. There were no significant differences between patients with and those without pseudarthrosis, respectively, for patient age (54.1 vs 53.8 years), sex (34.9% vs 47.4% male), race, prior cervical spine surgery (37.2% vs 33.6%), tobacco abuse (16.3% vs 14.5%), chronic kidney disease (2.3% vs 2.8%), and diabetes (18.6% vs 14.5%) (p > 0.05). Presence of osteopenia or osteoporosis (16.3% vs 3.5%) was associated with pseudarthrosis (p < 0.001). Implant type was also significantly associated with pseudarthrosis, with a 16.4% rate of pseudarthrosis for patients with polyetherethereketone (PEEK) implants versus 8.4% for patients with allograft implants (p = 0.04). Average lengths of follow-up were 27.6 and 23.8 months for patients with and those without pseudarthrosis, respectively. Multivariate analysis demonstrated osteopenia or osteoporosis (OR 4.97, 95% CI 1.51-16.4, p < 0.01) and usage of PEEK implant (OR 2.24, 95% CI 1.04-4.83, p = 0.04) as independent predictors of pseudarthrosis. CONCLUSIONS: In patients who underwent single-level ACDF, rates of pseudarthrosis associated with the use of the osteobiologic agent Osteocel are higher than the literature-reported rates associated with the use of alternative osteobiologics. This is especially true when Osteocel is combined with a PEEK implant.

Interhospital transfer status for spinal metastasis patients in the United States is associated with more severe clinical presentations and higher rates of inpatient complications.

OBJECTIVE: In patients with metastatic spinal disease (MSD), interhospital transfer can potentially impact clinical outcomes as the possible benefits of transferring a patient to a higher level of care must be weighed against the negative effects associated with potential delays in treatment. While the association of clinical outcomes and transfer status has been examined in other specialties, the relationship between transfer status, complications, and risk of mortality in patients with MSD has yet to be explored. The purpose of this study was to examine the impact of transfer status on in-hospital mortality and clinical outcomes in patients diagnosed with MSD. METHODS: The National (Nationwide) Inpatient Sample (NIS) database was retrospectively queried for adult patients diagnosed with vertebral pathological fracture and/or spinal cord compression in the setting of metastatic disease between 2012 and 2014. Demographics, baseline characteristics (e.g., metastatic spinal cord compression [MSCC] and paralysis), comorbidities, type of intervention, and relevant patient outcomes were controlled in a multivariable logistic regression model to analyze the association of transfer status with patient outcomes. RESULTS: Within the 10,360 patients meeting the inclusion and exclusion criteria, higher rates of MSCC (50.2% vs 35.9%, p < 0.001) and paralysis (17.3% vs 8.4%, p < 0.001) were observed in patients transferred between hospitals compared to those directly admitted. In univariable analysis, a higher percentage of transferred patients underwent surgical intervention (p < 0.001) when compared with directly admitted patients. After controlling for significant covariates and surgical intervention, transferred patients were more likely to develop in-hospital complications (OR 1.34, 95% CI 1.18-1.52, p < 0.001), experience prolonged length of stay (OR 1.33, 95% CI 1.16-1.52, p < 0.001), and have a discharge disposition other than home (OR 1.70, 95% CI 1.46-1.98, p < 0.001), with no significant difference in inpatient mortality rates. CONCLUSIONS: Patients with MSD who were transferred between hospitals demonstrated more severe clinical presentations and higher rates of inpatient complications compared to directly admitted patients, despite demonstrating no difference in in-hospital mortality rates.

Robotic-assisted percutaneous iliac screw fixation for destructive lumbosacral metastatic lesions: an early single-institution experience.

BACKGROUND: Robotic-assisted surgery is becoming more widely applied in surgical subspecialties due to its intraoperative and postoperative advantages such as minimally invasive approach, reduced blood loss, shorter hospital stay, and decreased incidence of postoperative complications. However, robotic devices were only recently introduced in the field of spinal surgery. Specifically, percutaneous approaches involving computer-assisted image guidance are relatively new in iliac screw fixation. Previous methods focused on the use of S2-alar-iliac (S2AI) screw fixation which allows for pelvic fixation without a need for side connectors. However, for patients with destructive lesions of the sacrum, placement of these S2AI screws may not be feasible. The purpose of this technical note is to illustrate the implementation of robotic-assisted percutaneous iliac screw fixation in two cases which allows for minimally invasive attachment to the proximal lumbar screws without a side connector and eliminates a potential source of instrumentation failure. METHODS: Robotic-assisted percutaneous iliac screw fixation was performed on two patients. The robotics system was used to merge the fluoroscopic images with intraoperative computed tomography (CT) images to plan the trajectories for placement of bilateral pedicle and iliac screws. Intraoperative CT scan was again performed to confirm proper placement of all screws. Rods were then engaged bilaterally with the pedicle and iliac screws without the use of side connectors. RESULTS: The patients did not experience immediate postoperative complications and had stable hardware at one-month follow-up. Our cases demonstrate the surgical efficiency of robotic-assisted lumbo-iliac instrumentation which obviates the need to use a side connector, which is commonly used in iliac fixation. This eliminates a step, which can reduce the possibility of instrumentation failure. CONCLUSION: Robotic-assisted percutaneous iliac screw fixation is a safe and feasible technique to improve operative and clinical outcomes in complex spinal instrumentation surgeries.

Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration.

Proteomics studies have revealed that SUMOylation is a widely used post-translational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown. Using a human proteome microarray-based activity screen, we identified over 2500 proteins that undergo SUMO E3-dependent SUMOylation. We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network. Protein kinases were significantly enriched among SUMOylation substrates, suggesting crosstalk between phosphorylation and SUMOylation. Cell-based analyses of tyrosine kinase, PYK2, revealed that SUMOylation at four lysine residues promoted PYK2 autophosphorylation at tyrosine 402, which in turn enhanced its interaction with SRC and full activation of the SRC-PYK2 complex. SUMOylation on WT but not the 4KR mutant of PYK2 further elevated phosphorylation of the downstream components in the focal adhesion pathway, such as paxillin and Erk1/2, leading to significantly enhanced cell migration during wound healing. These studies illustrate how our SUMO E3 ligase-substrate network can be used to explore crosstalk between SUMOylation and other PTMs in many biological processes.

The medicolegal impact of misplaced pedicle and lateral mass screws on spine surgery in the United States.

Spine surgery has been disproportionately impacted by medical liability and malpractice litigation, with the majority of claims and payouts related to procedural error. One common area for the potential avoidance of malpractice claims and subsequent payouts involves misplaced pedicle and/or lateral mass instrumentation. However, the medicolegal impact of misplaced screws on spine surgery has not been directly reported in the literature. The authors of the current study aimed to describe this impact in the United States, as well as to suggest a potential method for mitigating the problem.This retrospective analysis of 68 closed medicolegal cases related to misplaced screws in spine surgery showed that neurosurgeons and orthopedic spine surgeons were equally named as the defendant (n = 32 and 31, respectively), and cases were most commonly due to misplaced lumbar pedicle screws (n = 41, 60.3%). Litigation resulted in average payouts of $1,204,422 ± $753,832 between 1995 and 2019, when adjusted for inflation. The median time to case closure was 56.3 (35.2-67.2) months when ruled in favor of the plaintiff (i.e., patient) compared to 61.5 (51.4-77.2) months for defendant (surgeon) verdicts (p = 0.117).

Association of neurologic deficits with surgical outcomes and health-related quality of life after treatment for metastatic epidural spinal cord compression.

BACKGROUND: A critical knowledge gap exists regarding the impact of neurologic deficits on surgical outcomes and health-related quality of life (HRQOL) for patients surgically treated for metastatic epidural spinal cord compression (MESCC). METHODS: This prospective, multicenter and international study analyzed the impact of the neurologic status on functional status, HRQOL, and postoperative survival. The collected data included the patient demographics, overall survival, American Spinal Injury Association (ASIA) impairment scale, Spinal Instability Neoplastic Score, treatment details and complications and HRQOL measures, including version 2 of the 36-Item Short Form Health Survey (SF-36v2) and version 2.0 of the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0). RESULTS: A total of 239 patients surgically treated for spinal metastases were included. Six weeks after treatment, 99 of the 108 patients with a preoperative ASIA grade of E remained stable, 8 deteriorated to ASIA D, and 1 deteriorated to ASIA A. Of 55 patients with ASIA D, 27 improved to ASIA E, 27 remained stable and 1 deteriorated to ASIA C. Of 11 patients with ASIA A to C, 2 improved to ASIA E, 4 improved to ASIA D, and 5 remained stable. At the 6- and 12-week follow-up, better ASIA scores were associated with better scores on multiple SF-36v2 and SOSGOQ items. Postoperatively, patients with ASIA grades of A to D were more likely to have urinary tract infections and wound complications. Patients with a baseline ASIA grade of E or D survived significantly longer. CONCLUSIONS: Patients with neurologic deficits due to MESCC have worse HRQOL and decreased overall survival. Nevertheless, surgery can result in stabilization or improvement of neurologic function which may translate into better HRQOL. Postoperative care and follow-up are challenging for patients with neurologic deficits because they experience more complications.

Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms.

PURPOSE: Prostate circulating tumor cells escape into peripheral blood and enter bone marrow as disseminated tumor cells, representing an early step before conventionally detectable metastasis. It is unclear how frequently this occurs in localized disease and existing detection methods rely on epithelial markers with low specificity and sensitivity. We used multiple methodologies of disseminated tumor cell detection in bone marrow harvested at radical prostatectomy. MATERIALS AND METHODS: Bone marrow was harvested from 208 clinically localized cases, 16 controls and 5 metastatic cases with peripheral blood obtained from 37 metastatic cases. Samples were evaluated at 4 centers with 4 distinct platforms using antibody enrichment with the AdnaTest (Qiagen®) or VERSA (versatile exclusion based rare sample analysis), or whole sample interrogation with the RareCyte platform (Seattle, Washington) or HD-SCA (high definition single cell assay) using traditional epithelial markers and prostate specific markers. We investigated the sensitivity and specificity of these markers by evaluating expression levels in control and metastatic cases. RESULTS: EpCAM, NKX3.1 and AR were nonspecifically expressed in controls and in most samples using AdnaTest with no relation to perioperative variables. Only 1 patient with localized disease showed positive results for the prostate specific marker PSA. With the VERSA platform no localized case demonstrated disseminated tumor cells. With the RareCyte and HD-SCA platforms only a single patient had 1 disseminated tumor cell. CONCLUSIONS: Evaluation across multiple platforms revealed that epithelial markers are nonspecific in bone marrow and, thus, not suitable for disseminated tumor cell detection. Using prostate specific markers disseminated tumor cells were typically not detected in patients with localized prostate cancer.

Risk factors associated with short-term complications and mortality after pediatric spinal arthrodesis.

OBJECTIVE Spinal arthrodesis is routinely performed in the pediatric population. However, there is limited information on the short-term outcomes of pediatric patients who have undergone spine fusion. Thus, the authors conducted a retrospective review of the Pediatric National Surgical Quality Improvement Program (NSQIP) database to determine the short-term mortality, complication, reoperation, and readmission rates of pediatric patients who underwent spinal arthrodesis for all indications. METHODS The Pediatric NSQIP database was queried for all patients who underwent spinal arthrodesis between 2012 and 2014. Patient demographics, comorbidities, body mass index, American Society of Anesthesiologists classification, and operative time were abstracted. Short-term mortality, reoperation, and readmission rates and complications were also noted. Univariate and multivariate analyses were performed to delineate patient risk factors that influence short-term mortality, complications, reoperation, and readmission rates. RESULTS A total of 4420 pediatric patients who underwent spinal fusion were identified. Common indications for surgical intervention included acquired/idiopathic scoliosis or kyphoscoliosis (71.2%) and genetic/syndromic scoliosis (10.7%). The mean patient age was 13.7 ± 2.9 years, and 70% of patients were female. The overall 30-day mortality was 0.14%. Multivariate analysis showed that female sex and pulmonary comorbidities significantly increased the odds of reoperation, with odds ratios of 1.43 and 1.78, respectively. CONCLUSIONS In the NSQIP database for pediatric patients undergoing spinal arthrodesis for all causes, there was a 3.6% unplanned reoperation rate, a 3.96% unplanned readmission rate, and a 9.0% complication rate. This analysis provides data for risk stratification of pediatric patients undergoing spinal arthrodesis, allowing for optimized care.

Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis.

OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3-9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5-6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

A Screen for Extracellular Signal-Regulated Kinase-Primed Glycogen Synthase Kinase 3 Substrates Identifies the p53 Inhibitor iASPP.

UNLABELLED: The Kaposi's sarcoma-associated herpesvirus (KSHV) LANA protein is essential for the replication and maintenance of virus genomes in latently KSHV-infected cells. LANA also drives dysregulated cell growth through a multiplicity of mechanisms that include altering the activity of the cellular kinases extracellular signal-regulated kinase (ERK) and glycogen synthase kinase 3 (GSK-3). To investigate the potential impact of these changes in enzyme activity, we used protein microarrays to identify cell proteins that were phosphorylated by the combination of ERK and GSK-3. The assays identified 58 potential ERK-primed GSK-3 substrates, of which 23 had evidence for in vivo phosphorylation in mass spectrometry databases. Two of these, SMAD4 and iASPP, were selected for further analysis and were confirmed as ERK-primed GSK-3 substrates. Cotransfection experiments revealed that iASPP, but not SMAD4, was targeted for degradation in the presence of GSK-3. iASPP interferes with apoptosis induced by p53 family members. To determine the importance of iASPP to KSHV-infected-cell growth, primary effusion lymphoma (PEL) cells were treated with an iASPP inhibitor in the presence or absence of the MDM2 inhibitor Nutlin-3. Drug inhibition of iASPP activity induced apoptosis in BC3 and BCBL1 PEL cells but did not induce poly(ADP-ribose) polymerase (PARP) cleavage in virus-negative BJAB cells. The effect of iASPP inhibition was additive with that of Nutlin-3. Interfering with iASPP function is therefore another mechanism that can sensitize KSHV-positive PEL cells to cell death. IMPORTANCE: KSHV is associated with several malignancies, including primary effusion lymphoma (PEL). The KSHV-encoded LANA protein is multifunctional and promotes both cell growth and resistance to cell death. LANA is known to activate ERK and limit the activity of another kinase, GSK-3. To discover ways in which LANA manipulation of these two kinases might impact PEL cell survival, we screened a human protein microarray for ERK-primed GSK-3 substrates. One of the proteins identified, iASPP, showed reduced levels in the presence of GSK-3. Further, blocking iASPP activity increased cell death, particularly in p53 wild-type BC3 PEL cells.