A. Karim Ahmed

Cellular GFP Toxicity and Immunogenicity: Potential Confounders in in Vivo Cell Tracking Experiments

Green Fluorescent protein (GFP), used as a cellular tag, provides researchers with a valuable method of measuring gene expression and cell tracking. However, there is evidence to suggest that the immunogenicity and cytotoxicity of GFP potentially confounds the interpretation of in vivo experimental data. Studies have shown that GFP expression can deteriorate over time as GFP tagged cells are prone to death. Therefore, the cells that were originally marked with GFP do not survive and cannot be accurately traced over time. This review will present current evidence for the immunogenicity and cytotoxicity of GFP in in vivo studies by characterizing these responses.

Impact of smoking on postoperative complications after anterior cervical discectomy and fusion

The relationship between smoking and the risk of postoperative complications among anterior cervical discectomy and fusion (ACDF) patients remains uncertain. We compared the postoperative complication rates following ACDF surgery among non-smokers, current smokers, and ever-smokers. Baseline and outcome data were obtained from the 2005- to 2014 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for patients over the age of 18 who underwent non-emergent ACDF surgery. Information on current smoking and ever-smoking status was extracted. Outcomes included development of at least one complication, development of a major complication, in-hospital mortality, and length of stay. ACDF patients were either current smokers (7847, 30.3%) or not current smokers (18,022, 69.7%); 33.0% of all patients (n=8542) had ever smoked. Current smoking status was not associated with increased odds of any one complication (P=0.584) or any major complication (P=0.138). In addition, using the number of pack-years as the primary independent variable, multivariate logistic regression analysis revealed that the number of pack-years was not significantly associated with greater odds of developing any one complication (P=0.276) or any major complication (P=0.334). However, ever-smoker status did present significantly higher odds of any major complication (OR, 1.333; 95% CI 1.007-1.764; P=0.044) than for non-smokers. These results suggest that any patient with a prior smoking history should be considered a higher risk surgical candidate when attempting ACDF.

Effect of Liberal Blood Transfusion on Clinical Outcomes and Cost in Spine Surgery Patients

BACKGROUND CONTEXT Blood transfusions in spine surgery are shown to be associated with increased patient morbidity. The association between transfusion performed using a liberal hemoglobin (Hb) trigger-defined as an intraoperative Hb level of ≥10 g/dL, a postoperative level of ≥8 g/dL, or a whole hospital nadir between 8 and 10 g/dL-and perioperative morbidity and cost in spine surgery patients is unknown and thus was investigated in this study. PURPOSE This study aimed to describe the perioperative outcomes and economic cost associated with liberal Hb trigger transfusion among spine surgery patients. STUDY DESIGN/SETTING This is a retrospective study. PATIENT SAMPLE The surgical billing database at our institution was queried for inpatients discharged between 2008 and 2015 after the following procedures: atlantoaxial fusion, anterior cervical fusion, posterior cervical fusion, anterior lumbar fusion, posterior lumbar fusion, lateral lumbar fusion, other procedures, and tumor-related surgeries. In total, 6,931 patients were included for analysis. OUTCOME MEASURES The primary outcome was composite morbidity, which was composed of (1) infection (sepsis, surgical-site infection, Clostridium difficile infection, or drug-resistant infection); (2) thrombotic event (pulmonary embolus, deep venous thrombosis, or disseminated intravascular coagulation); (3) kidney injury; (4) respiratory event; and (5) ischemic event (transient ischemic attack, myocardial infarction, or cerebrovascular accident). MATERIALS AND METHODS Data on intraoperative transfusion were obtained from an automated, prospectively collected anesthesia data management system. Data on postoperative hospital transfusion were obtained through a Web-based intelligence portal. Based on previous research, we analyzed the data using three definitions of a liberal transfusion trigger in patients who underwent red blood cell transfusion: a liberal intraoperative Hb trigger as a nadir Hb level of 10 g/dL or greater, a liberal postoperative Hb trigger as a nadir Hb level of 8 g/dL or greater, or a whole hospital nadir Hb level of 8-10 g/dL. Variables analyzed included in-hospital morbidity, mortality, length of stay, and total costs associated with a liberal transfusion strategy. RESULTS Among patients with a whole hospital stay nadir Hb between 8 and 10 g/dL, transfused patients demonstrated a longer in-hospital stay (median [interquartile range], 6 [5-9] vs. 4 [3-6] days; p<.0001) and a higher perioperative morbidity (n=145 [11.5%] vs. n=74 [6.1%], p<.0001) than those not transfused. Even after adjusting for age, gender, race, American Society of Anesthesiologists class, Charlson Comorbidity Index score, estimated blood loss, baseline Hb value, and surgery type, logistic regression analysis revealed that patients with a nadir Hb of 8-10 g/dL who were transfused had an independently higher risk of perioperative morbidity (odds ratio=2.11, 95% confidence interval, 1.44-3.09; p<.0001). Estimated additional costs associated with liberal trigger use, defined as a transfusion occurring in patients with a whole hospital stay nadir Hb of 8-10 g/dL, ranged from

Oncogenic MicroRNA-20a is downregulated by the HIF-1α/c-MYC pathway in IDH1 R132H-mutant glioma

202,675 to

Predicting survival for metastatic spine disease: a comparison of nine scoring systems

700,151 annually. CONCLUSIONS Transfusion using a liberal trigger is associated with increased morbidity, even after controlling for possible confounders. Our results suggest that modification of transfusion practice may be a potential area for improving patient outcomes and reducing costs.

Epstein-Barr virus-associated smooth muscle tumor involving the spine of an HIV-infected patient: Case report and review of the literature

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been identified as one of the earliest events in gliomagenesis, occurring in over 70% of low grade gliomas and are present in the vast majority of secondary glioblastoma (GBM) that develop from these low-grade lesions. The aim of this study was to investigate whether the IDH1 R132H mutation influences the expression of oncogenic miR-20a and shed light on the underlying molecular mechanisms. The findings of the current study demonstrate presence of the IDH1 R132H mutation in primary human glioblastoma cell lines with upregulated HIF-1α expression, downregulating c-MYC activity and resulting in a consequential decrease in miR-20a, which is responsible for cell proliferation and resistance to standard temozolomide treatment. Elucidating the mechanism of oncogenic miR-20a activity introduces its role among well-established signaling pathways (i.e. HIF/c-MYC) and may be a meaningful prognostic biomarker or target for novel therapies among patients with IDH1-mutant glioma.

Immediate improvement of intraoperative monitoring signals following CSF release for cervical spine stenosis: Case report

BACKGROUND CONTEXT Despite advances in spinal oncology, research in patient-based prognostic calculators for metastatic spine disease is lacking. Much of the literature in this area investigates the general predictive accuracy of scoring systems in heterogeneous populations, with few studies considering the accuracy of scoring systems based on patient specifics such as type of primary tumor. PURPOSE The aim of the present study was to compare the ability of widespread scoring systems to estimate both overall survival at various time points and tumor-specific survival for patients undergoing surgical treatment for metastatic spine disease in order to provide surgeons with information to determine the most appropriate scoring system for a specific patient and timeline. STUDY DESIGN This is a retrospective study. PATIENT SAMPLE Patients who underwent surgical resection for metastatic spine disease at a single institution were included. OUTCOME MEASURES Areas under the receiver operating characteristic curves were generated from comparison of actual survival of patients and survival as predicted by application of prevalent scoring systems. METHODS A preoperative score for all 176 patients was retrospectively calculated utilizing the Skeletal Oncology Research Group (SORG) Classic Scoring Algorithm, SORG Nomogram, original Tokuhashi, revised Tokuhashi, Tomita, original Bauer, modified Bauer, Katagiri, and van der Linden scoring systems. Univariate and multivariate Cox proportional hazard models were constructed to assess the association of patient variables with survival. Receiver operating characteristic analysis modeling was utilized to quantify the accuracy of each test at different end points and for different primary tumor subgroups. No funds were received in support of this work. The authors have no conflicts of interest to disclose. RESULTS Among all patients surgically treated for metastatic spine disease, the SORG Nomogram demonstrated the highest accuracy at predicting 30-day (area under the curve [AUC] 0.81) and 90-day (AUC 0.70) survival after surgery. The original Tokuhashi was the most accurate at predicting 365-day survival (AUC 0.78). Multivariate analysis demonstrated multiple preoperative factors strongly associated with survival after surgery for spinal metastasis. The accuracy of each scoring system in determining survival probability relative to primary tumor etiology and time elapsed since surgery was assessed. CONCLUSIONS Among the nine scoring systems assessed, the present study determined the most accurate scoring system for short-term (30-day), intermediate (90-day), and long-term (365-day) survival, relative to primary tumor etiology. The findings of the present study may be utilized by surgeons in a personalized effort to select the most appropriate scoring system for a given patient.

The Challenges of Renal Cell Carcinoma Metastatic to the Spine: A Systematic Review of Survival and Treatment:

Within the last two decades, there have been multiple reports of Epstein-Barr virus (EBV)-associated smooth muscle tumors in immunocompromised patients. This includes HIV-infected patients, post-transplant patients, and patients with congenital defects of their immune systems. Here we report the case of a 24-year-old African American female with congenital HIV presenting with progressive lower extremity weakness, constipation, aching pain in her shoulders, and subcostal anesthesia. Magnetic resonance imaging (MRI) revealed a large circumferential lesion extending from T1-T3 and a smaller left paraspinal lesion at C6-C7. The T1-T3 mass was excised via a right-sided costotransversectomy with laminectomy and fusion from T1-T3. Highly active antiretroviral therapy (HAART) was started postoperatively, and adjuvant radiotherapy was initiated but patient was lost to follow-up. Surgical pathology demonstrated a smooth muscle tumor diffuse nuclear positivity for EBV-encoded small RNA 1 by in situ hybridization. Although eight studies have reported HIV patients with EBV-associated smooth muscle tumors of the spine, to the authors knowledge, this is the first review comprised solely of patients with spinal involvement with the addition of our patient case.

Crizotinib and erlotinib inhibits growth of c-Met+/EGFRvIII+ primary human glioblastoma xenografts

Cervical spondylotic myelopathy (CSM) is a degenerative pathology characterized by partial or complete conduction block on intraoperative neuromonitoring. We describe a case treated using osseoligamentous decompression and durotomy for cerebrospinal fluid (CSF) release. Intraoperative monitoring demonstrated immediate signal improvement with CSF release, suggesting that clinical improvement in CSM may result from resolution of CSF flow anomalies.

Impact of frailty on complications in patients with thoracic and thoracolumbar spinal fracture

Study Design: Systematic review. Objectives: The objective of this systematic review was to answer 2 key questions: (1) What is the clinical presentation and probability of symptomatic improvement following treatment for patients with renal cell carcinoma (RCC) of the spine? (2) What is the overall survival of patients diagnosed with spinal metastases from RCC? Methods: A literature review was performed to identify articles that reported on survival, clinical outcomes, and/or prognostic factors in the RCC population with spinal metastases from 1986 to 2016. Results: Forty-eight articles (807 patients) were included. The Fuhrman Nuclear Grade has been significantly associated with survival in previous studies but was underpowered in the current study. The Memorial Sloan-Kettering Cancer Center Score (MSKCC/Motzer) was also underpowered in the current study. From the time of spinal metastasis, the mean and median survival for patients with previously diagnosed primary RCC was 8.75 and 11.7 months, respectively, whereas synchronously diagnosed patients (primary RCC and spinal metastasis) had a mean and median survival of 6.75 and 11 months, respectively. Patients with a “low” (0-8), “intermediate” (9-11), or “high” (12-15) revised Tokuhashi score at initial presentation had a median survival of 5.4, 11.7, and 32.9 months, respectively. Conclusion: Patients with either a synchronous or latent diagnosis of RCC survived greater than 6 months from the time of presentation. Initial Furhman grade, Tokuhashi score, and MSKCC/Motzer can be useful tools in informing patient-specific prognosis for those with metastatic RCC of the spine.