Intravenous and Oral Tranexamic Acid are Equivalent at Reducing Blood Loss in Thoracolumbar Spinal Fusion: A Prospective Randomized Trial Phase 2

Intravenous and oral tranexamic acid are equivalent at reducing blood loss in thoracolumbar spinal fusion: a prospective randomized trial. Discussion and Conclusion: Patients treated with IV and PO TXA experienced the same perioperative blood loss after spinal fusions. Given its lower cost, PO TXA represents an excellent alternative to IV TXA in patients undergoing elective posterior thoracolumbar fusion and may improve healthcare cost-efficiency in the studied population. Results: 91 patients received IV TXA and 80 patients received PO TXA. Patient demographic factors were similar between groups except for Age, Weight, and BMI. The mean reduction of hemoglobin was similar between IV and PO groups (3.48 g/dL vs. 3.19 g/dL, respectively; P = 0.004, equivalence). Similarly, the calculated blood loss was equivalent (1274 mL vs. 1206 mL, respectively; P = 0.001 equivalence). In addition, higher ASA (American Society of Anesthesiologists) level and longer surgical time were associated with more hemoglobin reduction (P = 0.01 and P \u3c 0.001, respectively) and blood loss (P \u3c 0.01 and P \u3c 0.001, respectively). Methods: A prospective randomized trial of patients enrolled at a university affiliated tertiary medical center between February 2017 and October 2018. 171 patients undergoing thoracolumbar fusion were randomized to receive 1.95g of PO TXA 2 hours preoperatively or 2g IV TXA (1g before incision and 1g before wound closure) intraoperatively. The sample was further stratified into 3 categories based on number of levels fused (1-2 level fusions, 3-5, and \u3e5). The primary outcome was the reduction of hemoglobin. Secondary outcomes included calculated blood loss, drain output, postoperative transfusion, complications, and length of hospital stay. Equivalence analysis was performed with a two one-sided test (TOST). A P-value of \u3c0.05 suggested equivalence between treatments.Introduction: The use of antifibrinolytic agents such as tranexamic acid (TXA) to decrease operative blood loss and allogenic blood transfusions is well documented in the literature. While evidence supports the use of intravenous (IV) and topical formulations of TXA in spine surgery, the use of oral (PO) TXA has not been studied. The objective of the study is to compare perioperative blood loss in patients undergoing elective posterior thoracolumbar fusion who were treated with IV versus PO TXA.https://scholarlycommons.henryford.com/merf2019clinres/1041/thumbnail.jp

Observational study of visual testing efficacy in detecting cannabis usage

Drug recognition and examination programs are widely used to detect drug impairment in motor vehicle operators. Visual tests are a key assessment in the detection of cannabis-related impairment. Participants were recruited via social media from the medical cannabis community in Southwestern Ontario, Canada. Twenty-two participants completed the full observational trial design. The majority (n = 13 or 59.1%) were male, with a mean age of 36 years (SD = 9.4; range: 24–59). Participants underwent the following protocol: 1) First round of testing (vital signs, bio sample collection, visual tests, subjective data, neurocognitive testing) (Baseline phase); 2) Consumption of cannabis via inhalation; 3) Second round of testing 30 minutes following consumption (THC phase); 4) Additional rounds of testing at 90, 150, and 210 minutes following consumption (Recovery phase). Visual assessment data and vital signs did not follow typical patterns associated with acute cannabis intoxication. With blood THC levels more than double the Canadian legal limit (5 ng/mL), visual testing results were not diagnostic for cannabis impairment, as participants maintained normal pupil sizes and normal ocular convergence patterns. Visual testing is a key component in standardized examinations used for detecting cannabis-related impairment in Canadian drivers; however, our data indicate that visual testing may not be an effective diagnostic tool for the specific population of medical cannabis users

Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Li, S., Raychaudhuri, S., Lee, S. A., Brockmann, M. M., Wang, J., Kusick, G., Prater, C., Syed, S., Falahati, H., Ramos, R., Bartol, T. M., Hosy, E., & Watanabe, S. Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses. Nature Communications, 12(1), (2021): 677, https://doi.org/10.1038/s41467-021-21004-x.Neurotransmitter is released synchronously and asynchronously following an action potential. Our recent study indicates that the release sites of these two phases are segregated within an active zone, with asynchronous release sites enriched near the center in mouse hippocampal synapses. Here we demonstrate that synchronous and asynchronous release sites are aligned with AMPA receptor and NMDA receptor clusters, respectively. Computational simulations indicate that this spatial and temporal arrangement of release can lead to maximal membrane depolarization through AMPA receptors, alleviating the pore-blocking magnesium leading to greater activation of NMDA receptors. Together, these results suggest that release sites are likely organized to activate NMDA receptors efficiently.e also thank the Marine Biological Laboratory and their Neurobiology course for supporting the initial set of experiments (course supported by National Institutes of Health grant R25NS063307). S.W. and this work were supported by start-up funds from the Johns Hopkins University School of Medicine, Johns Hopkins Discovery funds, and the National Science Foundation (1727260), the National Institutes of Health (1DP2 NS111133-01 and 1R01 NS105810-01A1) awarded to S.W. S.W. is an Alfred P. Sloan fellow, McKnight Foundation Scholar, and Klingenstein and Simons Foundation scholar. G.K. was supported by a grant from the National Institutes of Health to the Biochemistry, Cellular and Molecular Biology Program of the Johns Hopkins University School of Medicine (T32 GM007445) and is a National Science Foundation Graduate Research Fellow (2016217537). E.H. and T.M.B. are supported by CRCNS-NIH-ANR grant AMPAR-T. The EM ICE high-pressure freezer was purchased partly with funds from an equipment grant from the National Institutes of Health (S10RR026445) awarded to Scot C Kuo

Oral- is as Effective as Intravenous Tranexamic Acid at Reducing Blood Loss in Thoracolumbar Spinal Fusions: A Prospective Randomized Trial

STUDY DESIGN: A prospective randomized trial at a university affiliated tertiary medical center between February 2017 and March 2020. OBJECTIVE: Compare perioperative blood loss in patients undergoing elective posterior thoracolumbar fusion who were treated with IV versus PO TXA. SUMMARY OF BACKGROUND DATA: The use of antifibrinolytic agents such as tranexamic acid (TXA) to decrease operative blood loss and allogenic blood transfusions is well documented in the literature. While evidence supports the use of intravenous (IV) and topical formulations of TXA in spine surgery, the use of oral (PO) TXA has not been studied. METHODS: 261 patients undergoing thoracolumbar fusion were randomized to receive 1.95 g of PO TXA 2 hours preoperatively or 2 g IV TXA (1 g before incision and 1 g before wound closure) intraoperatively. The sample was further stratified into 3 categories based on number of levels fused (1-2 level fusions, 3-5, and \u3e5). The primary outcome was the reduction of hemoglobin. Secondary outcomes included calculated blood loss, drain output, postoperative transfusion, complications, and length of hospital stay. Equivalence analysis was performed with a two one-sided test (TOST). RESULTS: 137 patients received IV and 124 received PO TXA. The average age was 62 ± 13 years (Mean ± SD), including 141 females and 120 males. Revision cases comprised of 67% of the total sample. Patient demographic factors were similar between groups except for weight, BMI, and preoperative platelet count. The mean reduction of hemoglobin was similar between IV and PO groups (3.56 vs. 3.28 g/dL, respectively; P = 0.002, equivalence). IV TXA group had a higher transfusion rate compared to PO TXA group (22 patients [19%] vs. 12 patients [10%]; P = 0.03). In addition, IV group had longer length of stay (LOS) than PO group (4.4 vs. 3.7 days; P = 0.02). CONCLUSION: Patients treated with IV and PO TXA experienced the same perioperative blood loss after small and large spinal fusions. In subgroup analysis, the intermediate (3-5 level) spinal fusions had less blood loss with PO TXA than IV TXA. Given its lower cost, PO TXA represents a superior alternative to IV TXA in patients undergoing elective posterior thoracolumbar fusion and may improve healthcare cost-efficiency in the studied population. Level of Evidence: 1

Facet Sparing Foraminal Decompression Using the Flexible Shaver Foraminotomy System: Nerve Safety, Pain Relief, and Patient Satisfaction.

Background: A number of surgical options exist for decompressing lumbar foraminal stenosis. Flexible shaver foraminotomy is a recent addition to this armamentarium. While the foraminotomy device has been incorporated into clinical practice, the literature on its safety and efficacy remain limited. We aimed to evaluate nerve safety, pain relief, and patient satisfaction in a series of patients treated with the iO-Flex shaver system (Amendia, Inc., Marietta, Georgia). Methods: Thirty-one consecutive patients with lumbar foraminal stenosis underwent foraminal decompression using the flexible microblade shaver system at 62 neuroforamina. The shavers were inserted into each foramen using an open hemilaminotomy and fluoroscopic guidance. Nerve mapping via mechanomyography (MMG) was used to ensure nerve safety. Perioperative charts were reviewed to find the incidence of neurologic complications and to quantify pain relief. Average office-based follow-up was 5.3 months. A 3-item questionnaire was administered to assess patient satisfaction during late follow-up, which occurred at an average of 21 months. Results: No planned iO-Flex foraminotomies were aborted. Neurologic complications included transient dysesthetic pain in 1 patient (3.2%, Conclusions: Decompression of lumbar foramina using the flexible shaver system and MMG nerve mapping is safe and effective, although the short-term sensory complication with this technique may be higher than previously reported. Patient satisfaction with iO-Flex foraminotomy is comparable to reported satisfaction outcomes for traditional lumbar decompression. Level of Evidence: 4

Verification of nerve decompression using mechanomyography.

BACKGROUND CONTEXT: Assessment of nerve root decompression in surgery is largely based on visualization and tactile feedback. Often times, visualization can be limited, such as in minimally invasive surgery, and tactile feedback is a subjective assessment that makes the evaluation of successful nerve decompression difficult. Electromyography (EMG) has been proposed as an assessment tool, but EMG responses are often difficult to quantify. Alternatively, mechanomyography (MMG) provides a quantifiable response with high signal-to-noise ratio compared with EMG. MMG provides a sensitive tool to accurately quantify mechanical responses to motor action potentials generated by electrical stimulus, allowing more reliable assessment of nerve decompression. PURPOSE: The aim of this study was to assess the ability of MMG to quantitatively demonstrate successful nerve root decompression. STUDY DESIGN: Prospective cohort, Therapeutic Level III, Urban Level I Trauma Center. PATIENT SAMPLE: A total of 46 patients (72 affected nerve roots) undergoing decompression procedures for lower extremity radiculopathy caused by nerve root compression were enrolled in the study. The study population included 15 patients with herniated nucleus pulposus (HNP) and 31 with lateral recess stenosis (LRS). OUTCOME MEASURE: Visual analog scale (VAS) score. METHODS: A total of 72 nerves roots in 46 patients undergoing lumbar decompression procedures, for lower extremity radicular symptoms, were tested using MMG. Nerves were stimulated upstream from the compression site, and the lowest threshold current needed to generate a muscle response was determined. Signal response sizes were recorded before and after decompression. VAS scores were collected pre- and postoperatively. RESULTS: Of the patients, 90% (65/72) had elevated stimulation thresholds (\u3e1 milliamp [mA]) before decompression. After decompression, 98% of patients (64/65) with elevated current thresholds exhibited a drop in threshold of ≥1 mA (p\u3c.001). A postdecompression increase in response amplitude was recorded in all patients. VAS scores improved postdecompression (6.8 vs. 1.1, p\u3c.001) with a positive correlation between decreased stimulation thresholds and degree of improvement in VAS scores (p\u3c.001). CONCLUSION: MMG is an effective tool that can be used to differentiate normal and compressed nerves by quantifying the mechanomyographic response to a stimulating current. MMG allows one to measure the effect of decompression, judge its effectiveness in real time, and eliminate the subjectivity seen in tactile feedback methods. When the adequacy of decompression is uncertain, MMG can guide the surgeon toward additional or alternative procedures to ensure complete nerve root decompression

Project management turnover: causes and effects on project performance

Changes in management personnel - variously termed displacement, succession or just turnover- have been found by many to have significant negative effects on project performance. However, researchers have often ignored the organizational context of succession, the timing of succession relative to the organizational life cycle, and the type of transfer undertaken in control surfaces. It has also been suggested that the idea of specifically choosing a project manager to see the project completely through its life cycle needs to be discarded in favour of selecting at each phase point, a new project manager best suited to the anticipated project environment. To examine this further, a web-based survey was designed and developed from a detailed literature review, with 67 completed surveys collected, equating to a 45% response rate. This aimed to: find the reasons for project management turnover; examine the extent to which project management turnover is associated with a particular phase of the project life cycle; and investigate the effects of project management turnover on project performance. The most significant findings are that project management turnover occurs predominantly in the execution phase of the project life cycle and that the main reasons for the turnover event are career motives, including the need for personal development, and dissatisfaction with the organisational culture and project management role. The results confirm that the turnover event disrupts and negatively affects the performance of the project team, the project, and potentially negates the competitive advantage of organisations in which it occurs

Intravenous and Oral Tranexamic Acid Are Equivalent at Reducing Blood Loss in Thoracolumbar Spinal Fusion: A Prospective Randomized Trial.

STUDY DESIGN: A prospective randomized trial of patients enrolled at a university affiliated tertiary medical center between February and December 2017. OBJECTIVE: To compare perioperative blood loss in patients undergoing elective posterior thoracolumbar fusion who were treated with intravenous (IV) versus oral (PO) tranexamic acid (TXA). SUMMARY OF BACKGROUND DATA: The use of antifibrinolytic agents such as TXA to decrease operative blood loss and allogenic blood transfusions is well documented in the literature. While evidence supports the use of IV and topical formulations of TXA in spine surgery, the use of PO TXA has not been studied. METHODS: Eighty-three patients undergoing thoracolumbar fusion were randomized to receive 1.95 g of PO TXA 2 hours preoperatively or 2 g IV TXA (1 g before incision and 1 g before wound closure) intraoperatively. The sample was further stratified into three categories based on number of levels fused (1-2 level fusions, 3-5, and \u3e5). The primary outcome was the reduction of hemoglobin. Secondary outcomes included calculated blood loss, drain output, postoperative transfusion, complications, and length of hospital stay. Equivalence analysis was performed with a two one-sided test (TOST). A P-value of \u3c0.05 suggested equivalence between treatments. RESULTS: Fourty three patients received IV TXA and 40 patients received PO TXA. Patient demographic factors were similar between groups except for body mass index (BMI). The mean reduction of hemoglobin was similar between IV and PO groups (3.36 g/dL vs. 3.43 g/dL, respectively; P = 0.01, equivalence). Similarly, the calculated blood loss was equivalent (1235 mL vs. 1312 mL, respectively; P = 0.02, equivalence). Eight patients (19%) in IV TXA group received a transfusion compared with five patients in PO TXA group (13%) (P = 0.44). One patient (2% and 3% in IV and PO, respectively) in each group experienced a deep venous thrombosis/pulmonary embolism (P = 0.96). CONCLUSION: Patients treated with IV and PO TXA experienced the same perioperative blood loss after spinal fusions. Given its lower cost, PO TXA represents an excellent alternative to IV TXA in patients undergoing elective posterior thoracolumbar fusion and may improve healthcare cost-efficiency in the studied population. LEVEL OF EVIDENCE: 1

Cervical nerve root to foraminal size ratio correlates with post-surgical patient-reported outcomes

INTRODUCTION: Changes in cervical neural foraminal (CNF) dimensions are considered a key factor in development of cervical radiculopathy due to their role in nerve root compression. However, cadaveric and in vivo studies indicate considerable variation in the size of nerve roots as well [1, 2], which, intuitively, should affect their risk of being compressed by the foramina. Recent studies reported a small but significant difference in nerve size between asymptomatic and symptomatic patients [3]; however, the relationship of nerve root size with clinical outcomes has not been studied in patients who have received surgical treatment of degenerative disease in their cervical spine and are at a time point significant for development of adjacent segment disease. This pilot study examined such relationships. We hypothesize that nerve root size (alone or relative to foraminal size) is associated with clinical symptoms. METHODS: Under local IRB approval, clinical MRI images obtained, using a 3D BTFE sequence (1.5 T, 0.65x0.65x1.5 mm voxel size) from 11 patients (7F, 35-75 years; 4M, 44-66 years; a convenience group) who had previously underwent either arthroplasty with an artificial disc (n=1) or anterior cervical discectomy and fusion (n=10) at the C5-6 level were used. At the time of imaging, average time post-surgery was 6.5 years (sd ±1.7 years). Resliced anterolateral views were prepared from axial images using multiplanar reconstruction (MPR) tools in Synedra View (v. 16.0.0.2, Innsbruck, Austria). Views were constructed parallel to and passing through the left and right nerve roots (approximately 50 degrees oblique to the sagittal plane) at C3-4, C4-5, C5-6 and C6-7 levels. Freehand selection tool was used to delineate the nerve and the foramen (Fig. 1). Foraminal area (FA) and width (FW), nerve root area (NA) and width (NW) and nerve root to foramen ratios of these variables (N/F.A and N/F.W) were calculated. All foraminal, nerve root and foramen to nerve root ratio variables measured within a patient were averaged over left and right sides and spine levels to obtain a single composite variable of each type for each patient. Each patient was assessed using the following validated patient reported outcome measures [4]: the visual analogue scale (VAS) for neck and arm pain, the modified Japanese Orthopedic Association (mJOA) score [5], the Neck Disability Index (NDI), and the EuroQol EQ-5D score. The VAS and NDI assess for pain and functional disability directly related to neck and arm symptoms (higher worse). The mJOA is a disease specific scale for assessing myelopathy (higher better) and the EQ-5D is a general health assessment (higher worse). The relationship between survey and image parameters were examined using correlation and regression analyses. For survey variables with a binary outcome, the correlations were examined using logistic regression. RESULTS: The average (±sd) composite NA, NW, N/F.A and N/F.W were 6.31 ± 0.72 mm2, 1.71 ± 0.14 mm, 0.103 ± 0.022 and 0.297 ± 0.044, respectively. No spine level was significantly more represented than others in composite variables. Increased overall NDI score was associated with decreased FW (R= -0.65, p\u3c0.05) and increased N/F.W (R= 0.68, p\u3c0.05) (Fig. 2). Increased FW was also associated with decreased scores in sections of NDI related to pain intensity (R= -0.88, p\u3c0.001), driving (R= -0.67, p\u3c0.04) and recreation (R= -0.75, p\u3c0.02) as well as neck and arm pain VAS (R= - 0.82, p\u3c0.004 and R= -0.81, p\u3c0.005, respectively), while N/F.W was associated with increased scores in sections of NDI related to pain intensity (R= 0.68, p\u3c0.05), reading (R= 0.74, p\u3c0.04), driving (R= 0.74, p\u3c0.03) and recreation (R= -0.75, p\u3c0.02). Additionally, increased N/F.A was associated with increased neck pain VAS (R= 0.79, p\u3c0.02). None of the image variables were significantly associated with the overall EQ-5D scores. However, increased FW was associated with decreased usual activities subscore (R= -0.76, p\u3c0.02) and increased N/F.A was associated with increased pain and discom ort subscore (R= 0.72, p\u3c0.03) of the survey. None of the image variables were significantly associated with the overall mJOA scores, except for a marginally significant positive correlation for FW (p=0.055). However, increased FW was associated with increased leg numbness subscore (R= 0.73, p\u3c0.02), increased NA was associated with increased urination subscore (R= 0.71, p\u3c0.04) and increased N/F.W was associated with decreased trunk numbness subscore (R= -0.67, p\u3c0.05) of the survey. DISCUSSION: To our knowledge, this is the first data on nerve root dimensions obtained over 6 years after cervical spine surgery, offering a connection between clinical outcomes and dimensions of nerve roots relative to foramina. The post-operative time of the examinations is significant in that it represents the onset of adjacent segment disease after initial surgery [6]. Our nerve root width and area measurements are generally in agreement with those of others measured in vivo via ultrasonography [2, 3, 7, 8] or from cadavers via dissection [1, 9]. The size of nerve roots relative to foramina were associated with worsening overall NDI and specific pain subscores of NDI and EQ-5D surveys. As expected, this is partially attributable to smaller foramina alone. However, foraminal size did not correlate with all variables that nerve to foramen ratio variables did, indicating that nerve size has value independently from foraminal size. Width variables were associated with survey variables more frequently than did area variables. While it is possible that foraminal and nerve root width are indeed more important than their respective height or area, this may be a result of anisotropic resolution in the images providing a higher resolution in the width direction. When nerve size was considered alone, greater nerve width was associated with worse personal care, driving and work subscores of the NDI survey, consistent with the idea that a larger nerve may be associated with an increased risk of compression. Interestingly, however, greater nerve area was associated with a better bladder function in the mJOA survey. This, and correlations to subscores such as leg numbness may be coincidental or indicative of underlying neurodegenerative disease or response to injury [10] rather than a causal association to mechanical stress. These results are considered preliminary due to the low number of patients examined, particularly those who are significantly symptomatic. Also, the measurements could not be performed at all locations of the cervical spine due to image artifacts caused by implants [11]. Future work is needed to further optimize imaging protocols for measurement of neuro-foraminal dimension variables and determine cut-off values for prediction of clinical outcomes in a prospective cohort. (Figure Presented)