Domain-Specific Diaschisis: Lesions to Parietal Action Areas Modulate Neural Responses to Tools in the Ventral Stream.

Neural responses to small manipulable objects ("tools") in high-level visual areas in ventral temporal cortex (VTC) provide an opportunity to test how anatomically remote regions modulate ventral stream processing in a domain-specific manner. Prior patient studies indicate that grasp-relevant information can be computed about objects by dorsal stream structures independently of processing in VTC. Prior functional neuroimaging studies indicate privileged functional connectivity between regions of VTC exhibiting tool preferences and regions of parietal cortex supporting object-directed action. Here we test whether lesions to parietal cortex modulate tool preferences within ventral and lateral temporal cortex. We found that lesions to the left anterior intraparietal sulcus, a region that supports hand-shaping during object grasping and manipulation, modulate tool preferences in left VTC and in the left posterior middle temporal gyrus. Control analyses demonstrated that neural responses to "place" stimuli in left VTC were unaffected by lesions to parietal cortex, indicating domain-specific consequences for ventral stream neural responses in the setting of parietal lesions. These findings provide causal evidence that neural specificity for "tools" in ventral and lateral temporal lobe areas may arise, in part, from online inputs to VTC from parietal areas that receive inputs via the dorsal visual pathway.

Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration.

Although mesenchymal stem cells (MSCs) transplantation into the IVD (intervertebral disc) may be beneficial in inhibiting apoptosis of nucleus pulposus cells (NPCs) and alleviating IVD degeneration, the underlying mechanism of this therapeutic process has not been fully explained. The purpose of this study was to explore the protective effect of MSC-derived exosomes (MSC-exosomes) on NPC apoptosis and IVD degeneration and investigate the regulatory effect of miRNAs in MSC-exosomes and associated mechanisms for NPC apoptosis. MSC-exosomes were isolated from MSC medium, and its anti-apoptotic effect was assessed in a cell and rat model. The down-regulated miRNAs in apoptotic NPCs were identified, and their contents in MSC-exosomes were detected. The target genes of eligible miRNAs and possible downstream pathway were investigated. Purified MSC-exosomes were taken up by NPCs and suppressed NPC apoptosis. The levels of miR-21 were down-regulated in apoptotic NPCs while MSC-exosomes were enriched in miR-21. The exosomal miR-21 could be transferred into NPCs and alleviated TNF-α induced NPC apoptosis by targeting phosphatase and tensin homolog (PTEN) through phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Intradiscal injection of MSC-exosomes alleviated the NPC apoptosis and IVD degeneration in the rat model. In conclusion, MSC-derived exosomes prevent NPCs from apoptotic process and alleviate IVD degeneration, at least partly, via miR-21 contained in exosomes. Exosomal miR-21 restrains PTEN and thus activates PI3K/Akt pathway in apoptotic NPCs. Our work confers a promising therapeutic strategy for IVD degeneration.

Molecular and clinical characterization of PTPN2 expression from RNA-seq data of 996 brain gliomas.

BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas. RNA-seq data of a cohort of 325 patients with glioma were available from the Chinese Glioma Genome Atlas and 671 from The Cancer Genome Atlas. R language, GraphPad Prism 5, and SPSS 22.0 were used to analyze data and draw figures. RESULTS: PTPN2 transcript levels increased significantly with higher grades of glioma and in isocitrate dehydrogenase (IDH) wild-type and mesenchymal subtype gliomas. A comprehensive biological analysis was conducted, which indicated a crucial role of PTPN2 in the immune and inflammation responses in gliomas. Specifically, PTPN2 was positively associated with HCK, LCK, MHC II, and STAT1 but negatively related to IgG and interferon. Moreover, canonical correlation analysis showed a positive correlation of PTPN2 with infiltrating immune cells, such as macrophages, neutrophils, and CD8+ T cells. Clinically, higher levels of PTPN2 were associated with a worse overall survival both in patients with gliomas and glioblastomas. CONCLUSION: PTPN2 expression level was increased in glioblastomas and associated with gliomas of the IDH wild-type and mesenchymal subtype. There was a close correlation between PTPN2 and the immune response and inflammatory activity in gliomas. Our results show that PTPN2 is a promising immunotherapy target and may provide additional treatment strategies.

Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein.

OBJECTIVES: Circular RNAs (circRNAs) have been proven to function as competing endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression of miRNA target mRNAs. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of intervertebral disc degeneration (IVDD). METHODS: The role and mechanism of a circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and degenerative NP tissues from patients and rat models. The interaction between circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of-apoptosis protein (XIAP), was examined. RESULTS: The decreased expression of XIAP in the inflammatory cytokines-treated NP cells and the degenerative NP tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix. miR-200c regulated NP cell viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of miR-200c and functioned in NP cells through targeting miR-200c and XIAP. Intradiscal injection of circVMA21 alleviated IVDD in the rat model. CONCLUSIONS: CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and imbalance between anabolism and catabolism of extracellular matrix through miR-200c-XIAP pathway. It provides a potentially effective therapeutic strategy for IVDD.

The expression profile of PD-L1 and CD8+ lymphocyte in pituitary adenomas indicating for immunotherapy.

BACKGROUND: Pituitary adenomas (PAs) are the second most common brain tumors, and mostly are benign tumors. However, there exists subtypes of PAs refractory to common treatments, and need novel therapy. Programmed death 1 (PD-1) blockade has shown durable objective response in a variety of malignancies, and the key predictive markers for this immunotherapy were PD-L1 and CD8+ tumor-infiltrating lymphocyte (TILs) expression. To evaluate the potential immunotherapy for PAs, we investigated the expression of these two immune markers in PAs. METHODS: Immunohistochemistry (IHC) was performed to detect the expression of PD-L1 and CD8+ TILs in PAs. The ratio of positive expression of PD-L1 and CD8+ TILs was compared with chi-squared tests among different subtypes of PAs. The association between their expression profile and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate. RESULTS: One hundred and ninety one patients with PAs were retrospectively involved in this study, consisting of 106 non-functioning PAs (NF-PAs, 55.5%), 40 PRL-secreting PAs (PRL-PAs, 20.9%), 31 GH-secreting PAs (GH-PAs, 16.2%), 9 ACTH-secreting PAs (ACTH-PAs, 4.7%) and 5 plurihormonal adenomas (2.6%) respectively. 36.6% of them were PD-L1 positive and 86.9% were CD8+ TILs positive. The positive PD-L1 immunostaining presented more frequently in functioning PAs (58.8%), compared with that (34.3%) in nonfunctioning group (p = 0.000). Moreover, the rates of PD-L1 expression were more associated with increased blood levels of PRL, GH, ACTH and cortisol. Contrastly, positive CD8+ TILs immunostaining was only correlated with elevated blood level of GH. For the analysis of immune markers with pathological results, PD-L1 expression was associated with PRL and GH immunostaining and higher Ki-67 index. But CD8+ TILs was only correlated with PRL immunostaining. CONCLUSION: Our results showed that PD-L1 was frequently expressed in functioning PAs with association of aggressive behaviors in PAs. The immunotherapy could be a promising treatment option of PAs.

Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Diphtheria toxin-based targeted toxin therapy for brain tumors.

Targeted toxins (TT) are molecules that bind cell surface antigens or receptors such as the transferrin or interleukin-13 receptor that are overexpressed in cancer. After internalization, the toxin component kills the cell. These recombinant proteins consist of an antibody or carrier ligand coupled to a modified plant or bacterial toxin such as diphtheria toxin (DT). These fusion proteins are very effective against brain cancer cells that are resistant to radiation therapy and chemotherapy. TT have shown an acceptable profile for toxicity and safety in animal studies and early clinical trials have demonstrated a therapeutic response. This review summarizes the characteristics of DT-based TT, the animal studies in malignant brain tumors and early clinical trial results. Obstacles to the successful treatment of brain tumors include poor penetration into tumor, the immune response to DT and cancer heterogeneity.

Return to play after cervical spine injury in sports.

Spinal cord injuries (SCIs) resulting from sports now represent 8.9% of the total causes of SCI. Regardless of cause, there are bound to be return-to-play decisions to be made for athletes. Since catastrophic cervical spine injuries are among the most devastating injuries in all of sports, returning from a cervical spine injury is one of the most difficult decisions in sports medicine. Axial loading is the primary mechanism for catastrophic cervical spine injuries. Axial loading occurs as a result of intentional or unintentional head-down contact and spearing. Most would agree that the athlete returning to a contact or collision sport after a cervical spine injury must be asymptomatic, have full strength, and have full active range of motion; however, each situation is unique. The following review discusses the pathophysiology of these conditions and suggests guidelines for return to contact sports after traumatic cervical SCI.

Structure-based discovery of a novel inhibitor targeting the ß-catenin/Tcf4 interaction.

Overactivation or overexpression of ß-catenin in the Wnt (wingless) signaling pathway plays an important role in tumorigenesis. Interaction of ß-catenin with T-cell factor (Tcf) DNA binding proteins is a key step in the activation of the proliferative genes in response to upstream signals of this Wnt/ß-catenin pathway. Recently, we identified a new small molecule inhibitor, named BC21 (C(32)H(36)Cl(2)Cu(2)N(2)O(2)), which effectively inhibits the binding of ß-catenin with Tcf4-derived peptide and suppresses ß-catenin/Tcf4 driven reporter gene activity. This inhibitor decreases the viability of ß-catenin overexpressing HCT116 colon cancer cells that harbor the ß-catenin mutation, and more significantly, it inhibits the clonogenic activity of these cells. Down-regulation of c-Myc and cyclin D1 expression, the two important effectors of the Wnt/ß-catenin signaling, is confirmed by treating HCT116 cells with BC21. This compound represents a new and modifiable potential anticancer candidate that targets ß-catenin/Tcf-4 interaction.

Intracerebral infusion of the bispecific targeted toxin DTATEGF in a mouse xenograft model of a human metastatic non-small cell lung cancer.

The aim of this study is to investigate the anti-cancer effect of the bispecific diphtheria toxin (DT) based immunotoxin DTATEGF, which targets both the epidermal growth factor (EGF) receptor (EGFR) and the urokinase-type plasminogen activator (uPA) receptor (uPAR) in vitro and in vivo when delivered by convection-enhanced delivery (CED) via an osmotic minipump in a human metastatic non-small cell lung cancer (NSCLC) brain tumor mouse xenograft model. The effects of the bispecific immunotoxin DTATEGF, and monospecific DTAT, DTEGF and control DT at various concentrations were tested for their ability to inhibit the proliferation of human metastatic NSCLC PC9-BrM3 cells in vitro by MTT assay. A xenograft model of human metastatic NSCLC intracranial model was established in nude mice using the human NSCLC PC9-BrM3 cell line genetically marked with a firefly luciferase reporter gene. One microgram of DTATEGF in the treatment group or control DT in the control group was delivered intracranially by CED via an osmotic minipump. The bioluminescent imaging (BLI) was performed at day 7, 14, 1 month, 2 months, and 3 months. Kaplan-Meier survival curves for the two groups were generated. The brain tissue samples were stained by hematoxylin and eosin for histopathological assessment. In vitro, DTATEGF could selectively kill PC9-BrM3 cells and showed an IC(50) less than 0.001 nM, representing a more than 100- to 1000-fold increase in activity as compared to monospecific DTAT and DTEGF. In vivo, mice with tumors were treated intracranially with drug via CED where the results showed the treatment was successful in providing a survival benefit with the median survival of mice treated with DTATEGF being significantly prolonged relative to controls (87 vs. 63 days, P = 0.006). The results of these experiments indicate that DTATEGF kills the NSCLC PC9-BrM3 cell line in vitro, and when it is delivered via CED intracranially, it is highly efficacious against metastatic NSCLC brain tumors. DTATEGF is a safe and effective drug where further preclinical and clinical development is warranted for the management of metastatic brain tumors.

Laterally placed expandable interbody spacers with and without adjustable lordosis improve patient outcomes: A preliminary one-year chart review.

BACKGROUND/OBJECTIVES: Minimally invasive lateral lumbar interbody fusion (MIS LLIF) has been employed to treat degenerative disc disease, with reduced complication profiles in comparison to other open anterior and posterior techniques. The technique permits the use of larger, coronal-spanning interbody spacers to restore height and alignment. However, large static spacers have historically been associated with iatrogenic complications during trialing and insertion. Developments in expandable technology have the potential for incrementally larger increases in both height and lordosis in a controlled expansion in situ, minimizing endplate violation. However, further clinical and radiographic data are needed to investigate the effect of expansion technology. METHODS: A retrospective, single-surgeon chart review was performed on 103 consecutive patients, all of whom underwent MIS LLIF surgery at 1-2 contiguous level(s) with expandable spacers [66/103 patients were implanted with lordotically actuated (adjustable lordosis) spacers, and 37/103 with non-adjustable lordosis spacers]. Clinical and radiographic functional outcomes were collected and compared at both preoperative and postoperative time points up to 12-month follow-up. Parametric and nonparametric tests were utilized when they were appropriate, with a P value < 0.05 being significant. RESULTS: One-hundred twenty-five levels were instrumented on 103 consecutive cases. Average age was 58.2 ± 12.1 years; 42.1% (45/107) were female; 78.6% (81/103) were 1-level cases; 21.4% (22/103) were 2-level cases; 44.8% (56/125) were performed at L4-L5 and 34.4% (43/125) at L3-4. Average estimated blood loss was 24.6 ± 12.3cc. Mean operative time was 61.0 ± 19.1 min, and mean fluoroscopic time was 28.2 ± 14.6 s. Visual Analog Scale (VAS) back and leg pain scores decreased significantly by an average of 6.5 ± 1.3 points at 12 months (P < 0.001). Oswestry Disability Index (ODI) scores significantly decreased at final follow-up by a mean of 62.0 ± 12.4 points (P < 0.001). Lumbar lordosis significantly improved by a mean of 3.1 ± 8.8°, while segmental lordosis significantly improved by 3.9 ± 3.1° at 12 months (P < 0.001). Anterior, middle, and posterior disc heights all experienced significant increases at 12 months by averages of 5.1 ± 3.1, 4.5 ± 2.9, and 2.4 ± 2.2 mm, respectively (P < 0.001). Neuroforaminal height significantly increased at 12 months by a mean of 3.7 ± 3.7 mm (P < 0.001). There was 99% fusion at all levels, with no findings of radiolucency and 1% pseudarthrosis observed. Only 1 (1/125, 0.8%) case of subsidence and 7 (7/125, 5.6%) cases of suspected, asymptomatic radiographic adjacent segment degeneration were reported, with no secondary revision surgeries through 12-month follow-up. CONCLUSION: Significant improvement of disc height, neuroforaminal height, segmental lordosis, and indirect decompression was achieved and maintained up to 1-year follow-up from baseline. Clinical outcomes were significantly improved based on appreciable decreases in VAS pain and ODI scores at final follow-up. Minimal complications were reported, with significant radiographic and patient reported outcomes observed. The use of expandable spacers, with and without adjustable lordosis, was shown to improve outcomes for the studied patient population.

Spontaneous acute subdural hematoma as the initial manifestation of chronic myeloid leukemia.

Spontaneous acute subdural hematoma is rare and limited to sporadic case reports, associated with neoplasm, aneurysm, arteriovenous malformation and cocaine use. Subdural hematoma has also been reported in association with leukemic malignancies, either during therapy or after diagnosis. However, there are no reports of spontaneous acute subdural hematoma as the primary initial presenting manifestation of a chronic myeloid leukemia. Here we describe one case of a 53-year-old male that presented with severe right-sided headache and intermittent left-sided paresthesias. CT scan showed non-traumatic right-sided acute subdural hematoma. Further evaluation revealed that the patient had chronic myeloid leukemia. His peripheral white blood count normalized after Gleevec and hydroxyurea chemotherapy. Furthermore, he had no neurological deficits after his subdural collection was adequately evacuated.

Familial Chiari malformation: case series.

Chiari malformations (Types I-IV) are abnormalities of the posterior fossa that affect the cerebellum, brainstem, and the spinal cord with prevalence rates of 0.1%-0.5%. Case reports of familial aggregation of Chiari malformation, twin studies, cosegregation of Chiari malformation with known genetic conditions, and recent gene and genome-wide association studies provide strong evidence of the genetic underpinnings of familial Chiari malformation. The authors report on a series of 3 family pairs with Chiari malformation Type I: 2 mother-daughter pairs and 1 father-daughter pair. The specific genetic causes of familial Chiari malformation have yet to be fully elucidated. The authors review the literature and discuss several candidate genes. Recent advances in the understanding of the genetic influences and pathogenesis of familial Chiari malformation are expected to improve management of affected patients and monitoring of at-risk family members.

Expandable Technology Improves Clinical and Radiographic Outcomes of Minimally Invasive Lateral Lumbar Interbody Fusion for Degenerative Disc Disease.

BACKGROUND: Static interbody spacers are standard of care for minimally invasive lateral lumbar interbody fusion (MIS LLIF). However, placement of large static interbody spacers typically requires multiple trialing, endplate preparation, and forceful impaction. A lateral expandable interbody spacer with adjustable lordosis can be inserted at a reduced height, to optimize the endplate-to-endplate fit. This study describes radiographic and clinical outcomes in patients treated using lateral titanium expandable interbody spacers with adjustable lordosis using MIS LLIF. METHODS: This is a single-surgeon, retrospective, institutional review board-exempt chart review of 24 consecutive patients who underwent MIS LLIF at 1-2 contiguous level(s) using expandable spacers with adjustable lordosis. Radiographic and clinical functional outcomes were collected and compared at preoperative and postoperative time points up to 24 months. Parametric and nonparametric tests were used when appropriate. Statistical results were significant if P < .05. RESULTS: Twenty-four consecutive patients were evaluated with an average age of 57.8 ± 12.6 years; 45.8% were female. Visual analog scale for back pain improved by 7.3 ± 1.0 points, whereas Oswestry Disability Index scores improved by a mean of 67.5 ± 11.3 points at 24 months (P < .001). Lumbar lordosis improved by a mean of 6.3 ± 10.1° at 24 months (P < .001). There were 29 spinal levels, with 41.4% at L4-5 and 34.5% at L3-4. Anterior, middle, and posterior disc height significantly increased at 24 months by means of 4.5 ± 2.9 mm, 4.0 ± 2.8 mm, and 2.6 ± 1.9 mm, respectively (P < .001). Neuroforaminal height significantly improved by 3.3 ± 3.9 mm at 24 months (P < .001). Segmental lordosis improved by 3.6 ± 3.0° at 24 months. CONCLUSIONS: This study showed significant positive clinical and radiographic outcomes for patients who underwent MIS LLIF using expandable interbody spacers with adjustable lordosis. Correction of sagittal alignment was achieved and maintained up to 2-year follow-up. The use of expandable spacers with adjustable lordosis was shown to be safe and effective in this cohort. LEVEL OF EVIDENCE: 3.

Comparative Effectiveness of Laterally Placed Expandable versus Static Interbody Spacers: A 1-Year Follow-Up Radiographic and Clinical Outcomes Study.

STUDY DESIGN: Retrospective chart review. PURPOSE: This study compared the clinical and radiographic outcomes of patients treated with expandable and static interbody spacers following minimally invasive lateral lumbar interbody fusion (MIS-LLIF) with 12-month follow-up. OVERVIEW OF LITERATURE: A common surgical option for the treatment of degenerative disk disease (DDD) is MIS-LLIF using static or expandable spacers to restore disk height (DH), neuroforaminal height (NH), and segmental lordosis. Static spacers may require excessive trialing and aggressive impaction, potentially leading to endplate disruption and subsidence. Expandable spacers allow for in situ expansion to help address complications associated with static spacers. METHODS: This is an Institutional Review Board-exempt review of 69 patients (static, n=32; expandable, n=37) diagnosed with DDD who underwent MIS-LLIF at 1-2 contiguous level(s) using static or expandable spacers. Radiographic and clinical outcomes were collected and compared at pre- and postoperative time points up to 12 months. RESULTS: The expandable group had a significantly higher mean change in Visual Analog Scale (VAS) scores at 6 weeks, 6 months, and 12 months vs. static (∆VAS at 12 months: expandable, 6.7±1.3; static, 5.1±2.6). Mean improvement of Oswestry Disability Index (ODI) scores at 3, 6, and 12 months were significantly better for the expandable group vs. static (∆ODI at 12 months: expandable, 63.2±13.2; static, 29.8±23.4). Mean DH and NH significantly increased at final follow-up for both groups, with no significant difference in DH improvement between groups. The expandable mean NH improvement at 6 weeks and 6 months was significantly greater vs. static. Segmental lordosis significantly improved in the expandable group at all time intervals vs static. Subsidence rate at 12 months was significantly lower in the expandable group (1/46, 2.2%) vs. static (12/37, 32.4%). CONCLUSIONS: Expandable spacers resulted in a significantly lower subsidence rate, improve segmental lordosis, and VAS and ODI outcomes at 12 months vs. static.

Retrospective Review of Revision Surgery After Image-guided Instrumented Spinal Surgery Compared With Traditional Instrumented Spinal Surgery.

STUDY DESIGN: Retrospective cohort series. OBJECTIVE: The objective of this study was to determine if the use of image-guided navigation offers a clinically significant advantage over fluoroscopy-assisted pedicle screw and non-navigated screw placement in reducing the risk of revision surgery for malpositioned screws in instrumented spinal surgery. SUMMARY OF BACKGROUND DATA: Use image-guided navigation has become increasingly commonplace in instrumented spine surgery, but there is a lack of information regarding differences in the rates of clinically relevant screw malposition with image-guided compared with non-navigated screw placement. MATERIALS AND METHODS: This is a retrospective cohort series of consecutive patients who underwent instrumented spinal surgery by the senior authors at 2 academic tertiary care centers in New York. RESULTS: A total of 663 instrumented spinal surgeries were analyzed, including 271 instances with image-guided navigation. For the image-guided navigation cohort, 110 of the patients underwent screw placement using O-Arm image-guidance, yielding data on 1115 screws. The remaining 161 surgeries utilizing image-guided screw placement were performed using Brainlab Spine Navigation, for a total of 1001 screws. A fluoroscopy-assisted technique or freehand technique was used in 419 instances, with a total of 3689 screws. Of the non-navigated cohort, 10 patients required a surgical revision of screw placement, for a total of 15 malpositioned screws. Amongst the image-guided navigation cohort, 1 patient in the O-Arm group and 2 in the Brainlab group required revision surgery, with 3 malpositioned screws in total. The rate of revision surgery for a malpositioned screw placed via non-navigated techniques was 2.39%. This risk was decreased to 1.11% with the use of the intraoperative image-guided navigation. However, no comparisons between non-navigated and image-guided screw placement reached statistical significance. CONCLUSION: Although not reaching statistical significance, these data suggest there may be an advantage offered by image-guided screw placement in instrumented spinal surgery.

Descriptive Analysis of 1972 Cervical Corpectomy Patients and 30-Day Postoperative Outcomes.

BACKGROUND: There exists no large, multi-institutional analysis of patients undergoing cervical corpectomy for common degenerative spinal disease, including patient demographics and comorbidities as well as postoperative complications. METHODS: Using Current Procedural Terminology and International Classification of Diseases codes, 1972 patients who underwent a cervical corpectomy for degenerative spinal disease were identified from the American College of Surgeons National Surgical Quality Improvement Program data sets from 2012 to 2015. A descriptive analysis of the patients who underwent the procedure as well as 30-day outcomes and adverse events were collected. Multivariate logistic regression models were used to determine the effect of any preoperative factors identified from a univariate logistic regression analysis (variables with P < .10) of complications. RESULTS: The total complication rate, defined as major or minor adverse event, mortality, unplanned readmission, unplanned reoperation, or admission >30 days, was 13.28%. The percentage of patients who had ≥1 major or minor adverse events was 5.02%. Several factors commonly associated with an increased risk of perioperative complications, including smoking and diabetes, were found not to be independently associated with complications in this cohort. CONCLUSIONS: This study is the largest analysis of cervical corpectomies. The results of the multivariate analysis provide guidance on risk factors associated with perioperative complications. These data could help develop risk-appropriate strategies for minimizing the effects of certain preoperative factors on perioperative complications.

Surgical Management and Adjuvant Therapy for Patients With Neurological Deficits From Vertebral Hemangiomas: A Meta-Analysis.

STUDY DESIGN: Meta-analysis. OBJECTIVE: To understand the benefits and limitations of surgical management and adjuvant therapies for patients presenting with neurological deficits from vertebral hemangiomas (VH). SUMMARY OF BACKGROUND DATA: VH is the most common benign spine tumor but rarely causes symptoms. Patients with back pain alone are treated with conservative management (kyphoplasty and radiation therapy), while those with neurological deficits require complex multi-modal treatment plans. METHODS: A PubMed literature search for "symptomatic vertebral hemangioma with spinal cord compression" identified 47 articles. From these articles and their references, 19 observational studies on patients who underwent surgery for VH met inclusion criteria. Meta-analyses were performed comparing outcomes of the surgical and adjuvant therapies using Stata13 software. For those with insufficient data for meta-analyses, descriptive analyses of variables were completed. RESULTS: One hundred ninety seven surgical cases of VH with neurologic deficits were identified. Surgery provided a complete remission of symptoms in 84% of patients, however 18% of patients had recurrence of hemangioma. Adjuvant interventions included radiation, embolization, and kyphoplasty. Radiation therapy (XRT) was associated with a lower recurrence rate and an increase in minor transient adverse effects. Preoperative embolization performed in 98 patients was associated with improved symptoms, reduced complications, lower recurrence rate, less blood loss, and higher incidence of pathologic vertebral fractures. Meta-analyses did not yield statistically significant results, likely due to the heterogeneity amongst the studies and small sample sizes, but the results compiled together provide insight on potential benefits of preoperative embolization for symptomatic relief and reduced risk of recurrence with XRT that deserves further study. CONCLUSION: For patients with neurologic deficits from spinal cord or nerve root compression, surgery provides improvement in symptoms. Recurrence of VH and symptoms refractory to surgery can be further reduced by adjuvant therapies such as embolization, kyphoplasty, and radiation with some unique risks to each therapy. LEVEL OF EVIDENCE: 2.

Second primary malignancies among cancer patients.

BACKGROUND: Rate of second primary malignancies (SPM) is steadily increasing over the last decades. New therapies, early diagnostic markers, screening tests for a larger number of individuals contribute to the increase prevalence of SPM. In the current study, we try to described the demographic composition of SPM victims, distribution of primary sites, and the impact of related factors on prognosis. METHODS: We conducted a retrospective study identifying patients over the age of 18 who were diagnosed with SPM from the 16 most common cancer sites between 2000 and 2013 from Surveillance, Epidemiology, and End Results data. Cox proportional hazards regression was used to analyze the relationship between different factors associated to the prognosis of SPM. Standard incidence rate of multiple primary (MP-SIR) was also calculated. RESULTS: A total of 303,753 patients were diagnosis with SPM and 76,168 of whom (25.08%) were included in our analytic cohort. Patients with prostate cancer was vulnerable to SPM, accounting for 34.59%, and SPM was prone to occur in lung and bronchus, accounting for 24.90%. The heat map shows that esophagus cancer survivors have the highest risk of developing stomachache tumors (SIR =5.08). The result of Cox regression suggests that a history of liver was associated with the shortest survival time (HR =1.64, 95% CI, 1.54-1.75, P<0.001). CONCLUSIONS: With the advancement of medical standards, the survival time of cancer patients is prolonged, but the occurrence of SPM is also increasing, and the prognosis is not optimistic. More attention needs to be invested in the prevention and treatment of SPM.

Risk factors and associated complications with unplanned intubation in patients with craniotomy for brain tumor.

Patients undergoing surgical resection of a brain tumor have the potential risk for beingintubated post-operatively, which may be associated with significant morbidity and/or mortality after surgery. This study was analyzed various preoperative patient characteristics, postoperative outcomes, and complications to identify risk factors for unplanned intubation (UI) in adult patients undergoing craniotomy for a brain tumor and created a risk score framework for that cohort. Patients undergoing surgery for a brain tumor were identified according to primary Current Procedural Terminology codes, and information found in The American College of Surgeons (ACS) National Surgical Quality Improvement Project (NSQIP) database from 2012 to 2015 was reviewed. A total of 18,642 adult brain tumor patients were included in the ACS-NSQIP. The rate of unplanned intubation in this cohort was 2.30% (4 2 8). The mortality rate of patients who underwent UI after surgical resection of brain tumor was 24.78% compared to an overall mortality of 2.46%. During the first 30 days after surgery, 33% of patients who underwent UI had an unplanned reoperation, compared to 4.76% of patients who did not undergo unplanned intubation. Bivariate and multivariate analyses identified several predictors and computed a risk score for UI. A risk score based on patient factors for those undergoing a craniotomy for a brain tumor predicts the postoperative UI rate. This could aid in surgical decision-making by identify patients at a higher risk of UI, while modifying perioperative management may help prevent UI.