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104. Zoledronic acid decreases infection burden in mouse model of spine implant Infection
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Proceedings of the 34th Annual Meeting of the North American Spine Society / The Spine Journal 19 (2019) S1−S58
Eve C. Tsai, MD, PhD, FRCSC9, Julio C. Furlan, MD, PhD10; 1 Saint John, NB, Canada; 2 Stan Cassidy Centre for Rehabilitation, Fredericton, NB, Canada; 3 Vancouver, BC, Canada; 4 Rick Hansen Institute, Vancouver, BC, Canada; 5 University of Manitoba/HSC, Winnipeg, MB, Canada; 6 University Health Network, Toronto, ON, Canada; 7 U of Western Ontario/London Health Sciences Centre, London, ON, Canada; 8 QE II Health Sciences Centre, Halifax, NS, Canada; 9 C2 Neurosciences Unit, Ottawa, ON, Canada; 10 Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada BACKGROUND CONTEXT: Traumatic cauda equina injury (TCEI) is usually caused by spine injury at L1 or below, and can result in motor and/ or sensory impairments and/or neurogenic bowel and bladder. PURPOSE: This study was undertaken to examine the factors that can potentially predict motor, sensory, bowel, and bladder function to aid in prognosis and optimal management. STUDY DESIGN/SETTING: Prospective cohort study. PATIENT SAMPLE: The study cohort included individuals with any neurological severity of injury (American Spinal Injury Association Impairment Scale [AIS] A to D) and single neurological levels from L1 up to and including S3 at admission to acute care at an RHSCIR facility as assessed using the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI). Patients were not required to have bowel and/or bladder dysfunction at admission to acute care. OUTCOME MEASURES: Lower extremity motor score (LEMS), neurological level of injury, and voluntary anal contraction (VAC) were obtained from the admission and discharge International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. Change in bowel and bladder function was assessed by the Functional Independence Measure (FIM), and walking status was assessed by either FIM or Spinal Cord Independence (SCIM) at admission and discharge. METHODS: Multiple logistic regression analysis was used to determine which of the following variables were associated with independent walking in a predictive model: age at the time of injury, sex, neurological level of injury (categorized as 3 groups), time from injury to surgery, LOS in an acute care facility, LOS in a rehabilitation facility, and rehabilitation onset. Multiple linear regression analyses were performed to determine which of the above variables were associated with the following dependent variables: (a) change in LEMS; and (b) change in bowel and bladder scores. Stepwise variable selection methods (p-values for a variable to enter and stay in the model set to 0.30 and 0.10 respectively) were applied to all regression models. Four final models obtained included significant predictors from stepwise variable. RESULTS: The cohort included 214 participants who were predominantly male (76.6%) with a mean age of 39.9§17.3 years who mostly had a fallrelated injury (48.8%) at the L1 neurological level (48.1%). Multiple logistic regression analysis indicated that independent walking at discharge was associated with male sex, surgery later than 24 hours from injury, and longer length of stay (LOS) in the acute and rehabilitation facilities. Multiple linear regression analysis showed that shorter time from injury to rehabilitation facilities and longer rehabilitation LOS were significant independent predictors of improvement in bowel function. Further, older age, female sex, and longer rehabilitation LOS were associated with improvement in bladder function. Greater LEMS improvement was associated with having a spine injury at the L1 level (vs L3-S3). CONCLUSIONS: Our results suggest that independent walking after TCEI is associated with sex, time of surgery, and in-patient LOS. Bowel and bladder function recovery was improved in those with longer rehabilitation LOS, and bladder function recovery was improved in females. Older age and longer time to surgery were associated with improved bladder function. This study provides key information for rehabilitation goal planning and communication with individuals and their families with regards to prognostication. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2019.05.116
Wednesday, September 25, 2019 2:05 − 3:05 PM Section on Biologics and Basic Research 104. Zoledronic acid decreases infection burden in mouse model of spine implant Infection Chad Ishmael, MD1, Peter P. Hsiue, MD2, Zachary Burke, MD3, Kellyn R. Hori, BS3, Justo Caballero, BS3, Vishal Hegde, MD2, Clark J. Chen, BS1, Brian K. Zukotynski, BS3, Sam I. Uweh, BS3, Cristina Villalpando, BS3, Nicolas A. Cevallos, BS4, Nicole Truong, BS5, Douglas M. Dang3, Alexandra Stavrakis, MD6, Nicholas Bernthal, MD7; 1 University of California Los Angeles, Los Angeles, CA, US; 2 UCLA Department of Orthopaedic Surgery, Los Angeles, CA, US; 3 Los Angeles, CA, US; 4 Bernthal Lab, Los Angeles, CA, US; 5 Orthopaedic Hospital Research Center, Los Angeles, CA, US; 6 Santa Monica, CA, US; 7 UCLA, Santa Monica, CA, US BACKGROUND CONTEXT: Bisphosphonates are commonly used in the orthopedic patient population to manage osteoporosis and other metabolic bone diseases. There is also increasing support for bisphosphonate use in the perioperative setting, to minimize osteolysis and bone loss. Additionally, bisphosphonates are known to affect the host immune system; however, their effect on implant infections, which are notoriously difficult to treat, remains largely unknown. PURPOSE: The purpose of this study was to assess the effect of zoledronic acid (ZA) on spinal implant infection in our validated mouse model. METHODS: Twenty-six 8-week-old C57BL/6 mice were included in the study. Twelve were treated with 250 ug/kg of ZA,12 with normal saline via retro-orbital injection on the day of surgery, and the remaining 2 were sterile controls. A stainless steel pin was then placed into the L4 spinous processes of all mice and site was inoculated with 1E+3 CFUs of bioluminescent Xen36 Staphylococcus aureus in experimental groups. Infection burden was monitored with in vivo bioluminescence imaging at pre-determined intervals. RESULTS: Following an initial similar increase after surgery and inoculation, mice treated with ZA showed a decreased bacterial burden as compared to infected control group (p<0.05) at all time points after postoperative day (POD) 3. This resulted in a significantly lower infection burden through POD 21 when both experimental group’s bioluminescence decreased to levels similar to that in sterile controls. CONCLUSIONS: The indications for ZA use continue to expand, and it is often used in the perioperative setting. In our validated mouse model of spine implant infection, ZA decreases bacterial burden as compared to controls. Further investigation is required to determine the effects of dosing, location of infection and to explore possible mechanisms by which ZA exerts this effect. These findings may suggest a further benefit to bisphosphonate use in the perioperative setting. FDA DEVICE/DRUG STATUS: Unavailable from authors at time of publication. https://doi.org/10.1016/j.spinee.2019.05.117
105. Sex-based differential response in rhBMP-2-mediated spinal fusion in vivo Mitchell Hallman, BA1, Jonathan T. Yamaguchi, BS2, David J. Ellenbogen, BA1, Allison Greene, BS3, Vivek P. Shah, BS4, Soyeon Jeong, MS5, Joseph G. Lynons, BS1, Mark A. Plantz, BS5, Tejas Nandurkar, MS1, Chawon Yun, PhD5, Wellington K. Hsu, MD5, Erin L. Hsu, PhD5; 1 Chicago, IL, US; 2 Hsu Lab, Simpson Querrey Institute, Chicago, IL, US; 3 NU FSM, Dept of Orthopaedic Surgery, Chicago, IL, US; 4 Robert H. Lurie Medical Research Center of Northwestern University, Chicago, IL, US; 5 Northwestern University, Chicago, IL, US BACKGROUND CONTEXT: Sex-based differences in clinical outcomes for spinal fusion have been investigated with conflicting results. Estrogen is well known to have a major influence on bone and interacts
Refer to onsite annual meeting presentations and postmeeting proceedings for possible referenced figures and tables. Authors are responsible for accurately reporting disclosure and FDA device/drug status at time of abstract submission.
Proceedings of the 34th Annual Meeting of the North American Spine Society / The Spine Journal 19 (2019) S1−S58
Eve C. Tsai, MD, PhD, FRCSC9, Julio C. Furlan, MD, PhD10; 1 Saint John, NB, Canada; 2 Stan Cassidy Centre for Rehabilitation, Fredericton, NB, Canada; 3 Vancouver, BC, Canada; 4 Rick Hansen Institute, Vancouver, BC, Canada; 5 University of Manitoba/HSC, Winnipeg, MB, Canada; 6 University Health Network, Toronto, ON, Canada; 7 U of Western Ontario/London Health Sciences Centre, London, ON, Canada; 8 QE II Health Sciences Centre, Halifax, NS, Canada; 9 C2 Neurosciences Unit, Ottawa, ON, Canada; 10 Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada BACKGROUND CONTEXT: Traumatic cauda equina injury (TCEI) is usually caused by spine injury at L1 or below, and can result in motor and/ or sensory impairments and/or neurogenic bowel and bladder. PURPOSE: This study was undertaken to examine the factors that can potentially predict motor, sensory, bowel, and bladder function to aid in prognosis and optimal management. STUDY DESIGN/SETTING: Prospective cohort study. PATIENT SAMPLE: The study cohort included individuals with any neurological severity of injury (American Spinal Injury Association Impairment Scale [AIS] A to D) and single neurological levels from L1 up to and including S3 at admission to acute care at an RHSCIR facility as assessed using the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI). Patients were not required to have bowel and/or bladder dysfunction at admission to acute care. OUTCOME MEASURES: Lower extremity motor score (LEMS), neurological level of injury, and voluntary anal contraction (VAC) were obtained from the admission and discharge International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. Change in bowel and bladder function was assessed by the Functional Independence Measure (FIM), and walking status was assessed by either FIM or Spinal Cord Independence (SCIM) at admission and discharge. METHODS: Multiple logistic regression analysis was used to determine which of the following variables were associated with independent walking in a predictive model: age at the time of injury, sex, neurological level of injury (categorized as 3 groups), time from injury to surgery, LOS in an acute care facility, LOS in a rehabilitation facility, and rehabilitation onset. Multiple linear regression analyses were performed to determine which of the above variables were associated with the following dependent variables: (a) change in LEMS; and (b) change in bowel and bladder scores. Stepwise variable selection methods (p-values for a variable to enter and stay in the model set to 0.30 and 0.10 respectively) were applied to all regression models. Four final models obtained included significant predictors from stepwise variable. RESULTS: The cohort included 214 participants who were predominantly male (76.6%) with a mean age of 39.9§17.3 years who mostly had a fallrelated injury (48.8%) at the L1 neurological level (48.1%). Multiple logistic regression analysis indicated that independent walking at discharge was associated with male sex, surgery later than 24 hours from injury, and longer length of stay (LOS) in the acute and rehabilitation facilities. Multiple linear regression analysis showed that shorter time from injury to rehabilitation facilities and longer rehabilitation LOS were significant independent predictors of improvement in bowel function. Further, older age, female sex, and longer rehabilitation LOS were associated with improvement in bladder function. Greater LEMS improvement was associated with having a spine injury at the L1 level (vs L3-S3). CONCLUSIONS: Our results suggest that independent walking after TCEI is associated with sex, time of surgery, and in-patient LOS. Bowel and bladder function recovery was improved in those with longer rehabilitation LOS, and bladder function recovery was improved in females. Older age and longer time to surgery were associated with improved bladder function. This study provides key information for rehabilitation goal planning and communication with individuals and their families with regards to prognostication. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2019.05.116
Wednesday, September 25, 2019 2:05 − 3:05 PM Section on Biologics and Basic Research 104. Zoledronic acid decreases infection burden in mouse model of spine implant Infection Chad Ishmael, MD1, Peter P. Hsiue, MD2, Zachary Burke, MD3, Kellyn R. Hori, BS3, Justo Caballero, BS3, Vishal Hegde, MD2, Clark J. Chen, BS1, Brian K. Zukotynski, BS3, Sam I. Uweh, BS3, Cristina Villalpando, BS3, Nicolas A. Cevallos, BS4, Nicole Truong, BS5, Douglas M. Dang3, Alexandra Stavrakis, MD6, Nicholas Bernthal, MD7; 1 University of California Los Angeles, Los Angeles, CA, US; 2 UCLA Department of Orthopaedic Surgery, Los Angeles, CA, US; 3 Los Angeles, CA, US; 4 Bernthal Lab, Los Angeles, CA, US; 5 Orthopaedic Hospital Research Center, Los Angeles, CA, US; 6 Santa Monica, CA, US; 7 UCLA, Santa Monica, CA, US BACKGROUND CONTEXT: Bisphosphonates are commonly used in the orthopedic patient population to manage osteoporosis and other metabolic bone diseases. There is also increasing support for bisphosphonate use in the perioperative setting, to minimize osteolysis and bone loss. Additionally, bisphosphonates are known to affect the host immune system; however, their effect on implant infections, which are notoriously difficult to treat, remains largely unknown. PURPOSE: The purpose of this study was to assess the effect of zoledronic acid (ZA) on spinal implant infection in our validated mouse model. METHODS: Twenty-six 8-week-old C57BL/6 mice were included in the study. Twelve were treated with 250 ug/kg of ZA,12 with normal saline via retro-orbital injection on the day of surgery, and the remaining 2 were sterile controls. A stainless steel pin was then placed into the L4 spinous processes of all mice and site was inoculated with 1E+3 CFUs of bioluminescent Xen36 Staphylococcus aureus in experimental groups. Infection burden was monitored with in vivo bioluminescence imaging at pre-determined intervals. RESULTS: Following an initial similar increase after surgery and inoculation, mice treated with ZA showed a decreased bacterial burden as compared to infected control group (p<0.05) at all time points after postoperative day (POD) 3. This resulted in a significantly lower infection burden through POD 21 when both experimental group’s bioluminescence decreased to levels similar to that in sterile controls. CONCLUSIONS: The indications for ZA use continue to expand, and it is often used in the perioperative setting. In our validated mouse model of spine implant infection, ZA decreases bacterial burden as compared to controls. Further investigation is required to determine the effects of dosing, location of infection and to explore possible mechanisms by which ZA exerts this effect. These findings may suggest a further benefit to bisphosphonate use in the perioperative setting. FDA DEVICE/DRUG STATUS: Unavailable from authors at time of publication. https://doi.org/10.1016/j.spinee.2019.05.117
105. Sex-based differential response in rhBMP-2-mediated spinal fusion in vivo Mitchell Hallman, BA1, Jonathan T. Yamaguchi, BS2, David J. Ellenbogen, BA1, Allison Greene, BS3, Vivek P. Shah, BS4, Soyeon Jeong, MS5, Joseph G. Lynons, BS1, Mark A. Plantz, BS5, Tejas Nandurkar, MS1, Chawon Yun, PhD5, Wellington K. Hsu, MD5, Erin L. Hsu, PhD5; 1 Chicago, IL, US; 2 Hsu Lab, Simpson Querrey Institute, Chicago, IL, US; 3 NU FSM, Dept of Orthopaedic Surgery, Chicago, IL, US; 4 Robert H. Lurie Medical Research Center of Northwestern University, Chicago, IL, US; 5 Northwestern University, Chicago, IL, US BACKGROUND CONTEXT: Sex-based differences in clinical outcomes for spinal fusion have been investigated with conflicting results. Estrogen is well known to have a major influence on bone and interacts
Refer to onsite annual meeting presentations and postmeeting proceedings for possible referenced figures and tables. Authors are responsible for accurately reporting disclosure and FDA device/drug status at time of abstract submission.