Analysis of Responses to Kava Kava in the Feline Pulmonary Vascular Bed

Alan D. Kaye,Jason M. Hoover,Ikhlass N. Ibrahim,Aaron M. Fields,Todd A. Richards 한국식품영양과학회 2006 Journal of medicinal food Vol.9 No.1

This study was designed to test the hypothesis that kava kava induces a depressor response in the pulmonaryvascular bed of the cat and to identify the pathways involved in the mediation or modulation of these effects. In separate ex-periments, the effects of L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO), a nitric oxide synthase inhibitor, glibenclamide,an ATP-sensitive K. channel blocker, meclofenamate, a nonselective cyclooxygenase inhibitor, nicardipine, a calcium chan-nel blocker, bicuculline, a .-aminobutyric acid (GABA)A receptor antagonist, and saclofen, a GABAB antagonist, were in-vestigated on pulmonary arterial responses to kava kava (kava), pinacidil, an ATP-sensitive K. channel activator, bradykinin,an inducer of nitric oxide synthase, 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF-97541), a GABAB receptoragonist, and muscimol, a GABAA receptor agonist. Lobar arterial perfusion pressure and systemic pressure were continuouslymonitored, electronically averaged, and recorded. Under elevated tone conditions in the isolated left lower lobe of the felinevascular bed, kava induced a dose-dependent vasodepressor response that was not significantly altered after administration ofL-NIO, glibenclamide, meclofenamate, or saclofen. Responses to kava were significantly reduced after administration of ei-ther nicardipine or bicuculline. When the calcium channel blocker nicardipine was administered in addition to the GABAblocker bicuculline, there was near complete attenuation of the kava-induced vasodepressor responses. The results of this in-vestigation suggest that kava has potent vasodepressor activity in the feline lung bed and that this response is mediated ormodulated by both a calcium channel- and GABA receptor-sensitive pathway.

Therapeutic lumbar facet joint nerve blocks in the treatment of chronic low back pain: cost utility analysis based on a randomized controlled trial

( Laxmaiah Manchikanti ),( Vidyasagar Pampati ),( Alan D. Kaye ),( Joshua A. Hirsch ) 대한통증학회 2018 The Korean Journal of Pain Vol.31 No.1

Background: Related to escalating health care costs and the questionable effectiveness of multiple interventions including lumbar facet joint interventions, cost effectiveness or cost utility analysis has become the cornerstone of evidence-based medicine influencing coverage decisions. Methods: Cost utility of therapeutic lumbar facet joint nerve blocks in managing chronic low back pain was performed utilizing data from a randomized, double-blind, controlled trial with a 2-year follow-up, with direct payment data from 2016. Based on the data from surgical interventions, utilizing the lowest proportion of direct procedural costs of 60%, total cost utility per quality adjusted life year (QALY) was determined by multiplying the derived direct cost at 1.67. Results: Patients in this trial on average received 5.6 ± 2.6 procedures over a period of 2 years, with average relief over a period of 2 years of 82.8 ± 29.6 weeks with 19 ± 18.77 weeks of improvement per procedure. Procedural cost for one-year improvement in quality of life showed USD $2,654.08. Estimated total costs, including indirect costs and drugs with multiplication of direct costs at 1.67, showed a cost of USD $4,432 per QALY. Conclusions: The analysis of therapeutic lumbar facet joint nerve blocks in the treatment of chronic low back pain shows clinical effectiveness and cost utility at USD $2,654.08 for the direct costs of the procedures, and USD $4,432 for the estimated overall cost per one year of QALY, in chronic persistent low back pain non-responsive to conservative management. (Korean J Pain 2018; 31: 27-38)

Serotonin Reuptake Inhibitor Increases Pseudarthrosis Rates in Anterior Cervical Discectomy and Fusions

Lambrechts Mark James,D'Antonio Nicholas,Toci Gregory,Karamian Brian,Pezzulo Josuhu,Farronato Dominic,Canseco Jose,Kaye Ian David,Woods Barrett,Rihn Jeffrey,Kurd Mark,Lee Joseph,Hilibrand Alan,Kepler 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.2

Study Design: Retrospective cohort.Purpose: To determine (1) the effects of serotonin reuptake inhibitors in pseudarthrosis rates after anterior cervical decompression and fusion (ACDF) and (2) to identify patient-reported outcome measures in patients taking serotonin reuptake inhibitors. Overview of Literature: Recent literature suggests that selective serotonin reuptake inhibitors (SSRIs) may inhibit fracture healing via downregulation of osteoblast differentiation. Spinal fusion supplementation with osteoblast-rich substances enhances spinal fusion, thus SSRIs may be detrimental.Methods: Patients with 1-year postoperative dynamic cervical spine radiographs following ACDF were grouped into serotonin reuptake inhibitor prescriptions (SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) and no prescription (atypical antidepressant or no antidepressant). Pseudarthrosis was defined as ≥1 mm interspinous process motion on dynamic radiographs. Logistic regression models were controlled for confounding to analyze pseudarthrosis rates. Alpha was set at p - values of <0.05.Results: Of the 523 patients who meet the inclusion criteria, 137 (26.2%) were prescribed an SSRI, SNRI, or TCA. Patients with these prescriptions were more likely to have pseudarthrosis (p =0.008) but not a revision surgery due to pseudarthrosis (p =0.219). Additionally, these patients had worse 1-year postoperative mental component summary (MCS)-12 (p =0.015) and Neck Disability Index (NDI) (p =0.006). The multivariate logistic regression analysis identified SSRI/SNRI/TCA use (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.11–2.99; p =0.018) and construct length (OR, 1.91; 95% CI, 1.50–2.44; p <0.001) as pseudarthrosis predictors. A SSRI/SNRI/TCA prescription was a revision surgery predictor due to adjacent segment disease on univariate analysis (OR, 2.51; p =0.035) but not on multivariate logistic regression analysis (OR, 2.24; p =0.10).Conclusions: Patients taking serotonin reuptake-inhibiting antidepressants are at increased risk of worse postoperative outcome scores, including NDI and MCS-12, likely due to their underlying depression. This may contribute to their greater likelihood of having adjacent segment surgery. Additionally, preoperative use of serotonin reuptake inhibitors in patients undergoing an ACDF is a predictor of radiographic pseudarthrosis but not pseudarthrosis revision.

Correction of Spinal Sagittal Alignment after Posterior Lumbar Decompression: Does Severity of Central Canal Stenosis Matter?

Trenchfield Delano,Lee Yunsoo,Lambrechts Mark J.,D’Antonio Nicholas,Heard Jeremy,Paulik John,Somers Sydney,Rihn Jeffrey A.,Kurd Mark,Kaye David,Canseco Jose,Hilibrand Alan,Vaccaro Alexander Richard,Ke 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.6

Study Design: This study adopted a retrospective study design.Purpose: Our study aimed to investigate the impact of central canal stenosis severity on surgical outcomes and lumbar sagittal correction after lumbar decompression.Overview of Literature: Studies have evaluated sagittal correction in patients with central canal stenosis after lumbar decompression and the association of stenosis severity with worse preoperative sagittal alignment. However, none have evaluated the impact of spinal stenosis severity on sagittal correction.Methods: Patients undergoing posterior lumbar decompression (PLD) of ≤4 levels were divided into severe and non-severe central canal stenosis groups based on the Lee magnetic resonance imaging (MRI) grading system. Patients without preoperative MRI or inadequate visualization on radiographs were excluded. Surgical characteristics, clinical outcomes, and sagittal measurements were compared. Multivariate logistic regression was performed to determine the predictors of pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), and pelvic incidence minus lumbar lordosis (PI–LL).Results: Of the 142 patients included, 39 had severe stenosis, and 103 had non-severe stenosis. The mean follow-up duration for the cohort was 4.72 months. Patients with severe stenosis were older, had higher comorbidity indices and levels decompressed, and longer lengths of stay and operative times (<i>p</i> <0.001). Although those with severe stenosis had lower lordosis, lower SS, and higher PI–LL mismatch preoperatively, no differences in Delta LL, SS, PT, or PI–LL were observed between the two groups (<i>p</i> >0.05). On multivariate regression, severe stenosis was a significant predictor of a lower preoperative LL (estimate=−5.243, <i>p</i> =0.045) and a higher preoperative PI–LL mismatch (estimate=6.192, <i>p</i> =0.039). No differences in surgical or clinical outcomes were observed (<i>p</i> >0.05).Conclusion: Severe central lumbar stenosis was associated with greater spinopelvic mismatch preoperatively. Sagittal balance improved in both patients with severe and non-severe stenosis after PLD to a similar degree, with differences in sagittal parameters remaining after surgery. We also found no differences in postoperative outcomes associated with stenosis severity.

A Comparison of Radiographic Alignment between Bilateral and Unilateral Interbody Cages in Patients Undergoing Transforaminal Lumbar Interbody Fusion

Lambrechts Mark James,Heard Jeremy,D’Antonio Nicholas,Bodnar John,Schneider Gregory,Bloom Evan,Canseco Jose,Woods Barrett,Kaye Ian David,Kurd Mark Faisal,Rihn Jeffrey,Hilibrand Alan,Schroeder Gregory 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.4

Study Design: Retrospective cohort study.Purpose: To compare radiographic outcomes between unilateral and bilateral cage placement in transforaminal lumbar interbody fusions (TLIF) and to determine if the rate of fusion at the 1-year postoperative point was different in patients who received bilateral versus unilateral cages.Overview of Literature: There is no clear evidence to dictate whether bilateral or unilateral cages promote superior radiographic or surgical outcomes in TLIF.Methods: Patients >18 years old who underwent primary one- or two-level TLIFs at our institution were identified and propensitymatched in a 3:1 fashion (unilateral:bilateral). Patient demographics, surgical characteristics, and radiographic outcomes, including vertebral endplate obliquity, segmental lordosis, subsidence, and fusion status, were compared between groups.Results: Of the 184 patients included, 46 received bilateral cages. Bilateral cage placement was associated with greater subsidence (1.06±1.25 mm vs. 0.59±1.16 mm, <i>p</i>=0.028) and enhanced restoration of segmental lordosis (5.74°±14.1° vs. −1.57°±10.9°, <i>p</i>=0.002) at the 1-year postoperative point, while unilateral cage placement was associated with an increased correction of endplate obliquity (−2.02°±4.42° vs. 0.24°±2.81°, <i>p</i><0.001). Bilateral cage placement was significantly associated with radiographic fusion on bivariate analysis (89.1% vs. 70.3%, <i>p</i>=0.018) and significantly predicted radiographic fusion on multivariable regression analysis (estimate, 1.35; odds ratio, 3.87; 95% confidence interval, 1.51–12.05; <i>p</i>=0.010).Conclusions: Bilateral interbody cage placement in TLIF procedures was associated with restoration of lumbar lordosis and increased fusion rates. However, endplate obliquity correction was significantly greater for patients who received a unilateral cage.

The role of percutaneous neurolysis in lumbar disc herniation: systematic review and meta-analysis

( Laxmaiah Manchikanti ),( Emilija Knezevic ),( Nebojsa Nick Knezevic ),( Mahendra R. Sanapati ),( Alan D. Kaye ),( Srinivasa Thota ),( Joshua A. Hirsch ) 대한통증학회 2021 The Korean Journal of Pain Vol.34 No.3

Background: Recalcitrant disc herniation may result in chronic lumbar radiculopathy or sciatica. Fluoroscopically directed epidural injections and other conservative modalities may provide inadequate improvement in some patients. In these cases, percutaneous neurolysis with targeted delivery of medications is often the next step in pain management. Methods: An evidence-based system of methodologic assessment, namely, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used. Multiple databases were searched from 1966 to January 2021. Principles of the best evidence synthesis were incorporated into qualitative evidence synthesis. The primary outcome measure was the proportion of patients with significant pain relief and functional improvement (≥ 50%). Duration of relief was categorized as short-term (< 6 months) and long-term (≥ 6 months). Results: This assessment identified one high-quality randomized controlled trial (RCT) and 5 moderate-quality non-randomized studies with an application of percutaneous neurolysis in disc herniation. Overall, the results were positive, with level II evidence. Conclusions: Based on the present systematic review, with one RCT and 5 nonrandomized studies, the evidence level is II for percutaneous neurolysis in managing lumbar disc herniation.

Incidence, Risk Factors, and Outcomes of Incidental Durotomy during Lumbar Spine Decompression with or without Fusion

Toci Gregory,Lambrechts Mark James,Issa Tariq,Karamian Brian Abedi,Siegel Nicholas,Antonio Nicholas D’,Canseco Jose,Kurd Mark,Woods Barrett,Kaye Ian David,Hilibrand Alan,Kepler Christopher,Vaccaro Ale 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.4

Study Design: Retrospective cohort study.Purpose: The primary objective of this study was to determine the incidence and risk factors for incidental durotomies during lumbar decompression surgeries. In addition, we aimed to determine the changes in patient-reported outcome measures (PROMs) based on incidental durotomy status.Overview of Literature: There is limited literature investigating the affect of incidental durotomy on patient reported outcome measures. While the majority of research does not suggest differences in complications, readmission, or revision rates, many studies rely on public databases, and their sensitivity and specificity for identifying incidental durotomies is unknown.Methods: Patients undergoing lumbar decompression with or without fusion at a single tertiary care center were grouped based on the presence of a durotomy. Multivariate analysis was performed for length of stay (LOS), hospital readmissions, and changes in PROMs. To identify surgical risk factors for durotomy, 3:1 propensity matching was performed using stepwise logistic regression. The sensitivity and specificity of the International Classification of Disease, 10th revision (ICD-10) codes (G96.11 and G97.41) were also assessed.Results: Of the 3,684 consecutive patients who underwent lumbar decompressions, 533 (14.5%) had durotomies, and a complete set of PROMs (preoperative and 1-year postoperative) were available for 737 patients (20.0%). Incidental durotomy was an independent predictor of increased LOS but not hospital readmission or worse PROMs. The durotomy repair method was not associated with hospital readmission or LOS. However, repair with collagen graft and suture predicted reduced improvement in Visual Analog Scale back (<i>β</i> =2.56, <i>p</i>=0.004). Independent risk factors for incidental durotomies included revisions (odds ratio [OR], 1.73; <i>p</i><0.001), levels decompressed (OR, 1.11; <i>p</i>=0.005), and preoperative diagnosis of spondylolisthesis or thoracolumbar kyphosis. The sensitivity and specificity of ICD-10 codes were 5.4% and 99.9%, respectively, for identifying durotomies.Conclusions: The durotomy rate for lumbar decompressions was 14.5%. No differences in outcomes were detected except for increased LOS. Database studies relying on ICD codes should be interpreted with caution due to the limited sensitivity in identifying incidental durotomies.

Significance of Facet Fluid Index in Anterior Cervical Degenerative Spondylolisthesis

Lee Yunsoo,Heard Jeremy C.,Lambrechts Mark J.,Kern Nathaniel,Wiafe Bright,Goodman Perry,Mangan John J.,Canseco Jose A.,Kurd Mark F.,Kaye Ian D.,Hilibrand Alan S.,Vaccaro Alexander R.,Kepler Christophe 대한척추외과학회 2024 Asian Spine Journal Vol.18 No.1

Study Design: Retrospective cohort study.Purpose: To correlate cervical facet fluid characteristics to radiographic spondylolisthesis, determine if facet fluid is associated with instability in cervical degenerative spondylolisthesis, and examine whether vertebral levels with certain facet fluid characteristics and spondylolisthesis are more likely to be operated on.Overview of Literature: The relationship between facet fluid and lumbar spondylolisthesis is well-documented; however, there is a paucity of literature investigating facet fluid in degenerative cervical spondylolisthesis.Methods: Patients diagnosed with cervical degenerative spondylolisthesis were identified from a hospital’s medical records. Demographic and surgical characteristics were collected through a structured query language search and manual chart review. Radiographic measurements were made on preoperative MRIs for all vertebral levels diagnosed with spondylolisthesis and adjacent undiagnosed levels between C3 and C6. The facet fluid index was calculated by dividing the facet fluid measurement by the width of the facet. Bivariate analysis was conducted to compare facet characteristics based on radiographic spondylolisthesis and spondylolisthesis stability.Results: We included 154 patients, for whom 149 levels were classified as having spondylolisthesis and 206 levels did not. The average facet fluid index was significantly higher in patients with spondylolisthesis (0.26±0.07 vs. 0.23±0.08, p <0.001). In addition, both fluid width and facet width were significantly larger in patients with spondylolisthesis (p <0.001 each). Cervical levels in the fusion construct demonstrated a greater facet fluid index and were more likely to have unstable spondylolisthesis than stable spondylolisthesis (p <0.001 each).Conclusions: Facet fluid index is associated with cervical spondylolisthesis and an increased facet size and fluid width are associated with unstable spondylolisthesis. While cervical spondylolisthesis continues to be an inconclusive finding, vertebral levels with spondylolisthesis, especially the unstable ones, were more likely to be included in the fusion procedure than those without spondylolisthesis.