2.Adreno-Muscarinic Synergy of Contractile Responses From Human Hyperplastic Prostate
Ben T. BLAKE-JAMES ; Basu CHAKRABARTY ; Christopher H. FRY
International Neurourology Journal 2024;28(Suppl 1):46-54
Purpose:
Adreno-muscarinic synergy, a supra-additional contractile response to simultaneous application of α-adrenoreceptor and muscarinic receptor agonists, is a feature of several lower urinary tract regions that have dual sympathetic and parasympathetic innervation. We tested the hypothesis that synergy is also a feature of prostate tissue obtained from men with benign prostatic enlargement.
Methods:
Isolated tissue strips were dissected from prostate ‘chips’, collected after transurethral prostate resection procedures for in vitro experiments, to measure isometric tension at 36°C.
Results:
Added separately to the superfusate, phenylephrine and carbachol generated contractions with mean pEC50 (-log10EC50) values of 5.36 and 5.58, respectively, although phenylephrine maximal responses were about six-fold greater. In the presence of carbachol, the mean phenylephrine pEC50 was significantly increased to 5.84 and maximal response increased by 28%; overall, a significant synergistic response was demonstrated. The synergistic response was reduced by muscarinic receptor antagonists, most potently by the M3-selective agent 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide), and less so by M2 and M1-selective inhibitors gallamine and pirenzepine, but with an overall profile indicating M3/M2 mediation of the synergistic response. The magnitude of the synergistic response was variable between prostate chips that provided isolated preparations suggesting regional heterogenicity, although their zonal origin could not be determined.
Conclusions
These experiments show that adreno-muscarinic contractile synergy is a feature of human hyperplastic prostate tissue. This has implications for the use of a combination therapy of α-blockers and anti-muscarinic agent to relieve secondary symptoms associated with benign prostatic hyperplasia, at least in men who can tolerate antimuscarinics without a risk of retention.
3.Symptomatic perianeursymal cyst development 20 years after endovascular treatment of a ruptured giant aneurysm: Case report and updated review
Amy J. WANG ; Justin E. VRANIC ; Robert W. REGENHARDT ; Adam A. DMYTRIW ; Christine K. LEE ; Cameron SADEGH ; James D. RABINOV ; Christopher J. STAPLETON
Journal of Cerebrovascular and Endovascular Neurosurgery 2024;26(2):187-195
Perianeurysmal cysts are a rare and poorly understood finding in patients both with treated and untreated aneurysms. While the prior literature suggests that a minority of perianeurysmal cysts develop 1-4 years following endovascular aneurysm treatment, this updated review demonstrates that nearly half of perianeurysmal cysts were diagnosed following aneurysm coiling, with the other half diagnosed concurrently with an associated aneurysm prior to treatment. 64% of perianeurysmal cysts were surgically decompressed, with a 39% rate of recurrence requiring re-operation. We report a case of a 71-year-old woman who presented with vertigo and nausea and was found to have a 3.4 cm perianeurysmal cyst 20 years after initial endovascular coiling of a ruptured giant ophthalmic aneurysm. The cyst was treated with endoscopic fenestration followed by open fenestration upon recurrence. The case represents the longest latency from initial aneurysm treatment to cyst diagnosis reported in the literature and indicates that the diagnosis of perianeurysmal cyst should remain on the differential even decades after treatment. Based on a case discussion and updated literature review, this report highlights proposed etiologies of development and management strategies for a challenging lesion.
4.Intracranial stenting compared to medical treatment alone for intracranial atherosclerosis patients: An updated meta-analysis
Adam A. DMYTRIW ; Jerry KU ; Ahmed Y. AZZAM ; Osman ELAMIN ; Nicole CANCELLIERE ; Anish KAPADIA ; James D. RABINOV ; Christopher J. STAPLETON ; Robert W. REGENHARDT ; Vitor Mendes PEREIRA ; Aman B. PATEL ; Victor X.D. YANG
Journal of Cerebrovascular and Endovascular Neurosurgery 2024;26(2):152-162
Objective:
Stroke is the second-leading cause of death globally. Intracranial atherosclerotic stenosis (ICAS) represents 10-15% of ischemic strokes in Western countries and up to 47% in Asian countries. Patients with ICAS have an especially high risk of stroke recurrence. The aim of this meta-analysis is to reassess recurrent stroke, transient ischemic attack (TIA), and other outcomes with stenting versus best medical management for symptomatic ICAS.
Methods:
The search protocol was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The OVID Medline, Embase, Web of Science, and Cochrane Library databases were searched from inception to August 14th, 2022.
Results:
This Meta-analysis Included Four Randomized Controlled Trials (Rcts), With A Total Number Of 991 Patients. The Mean Age Of Participants Was 57 Years. The Total Number Of Intracranial Stenting Patients Was 495, And The Number Of Medical Treatment Patients Was 496. The Included Studies Were Published Between 2011 And 2022. Two Studies Were Conducted In The Usa, And The Other Two In China. All Included Studies Compared Intracranial Stenting To Medical Treatment For Icas.
Conclusions
In patients with ischemic stroke due to symptomatic severe intracranial atherosclerosis, the rate of 30-day ischemic stroke, 30-day intracerebral hemorrhage, one-year stroke in territory or mortality favored the medical treatment alone without intracranial stenting. The risk of same-territory stroke at last follow-up, disabling stroke at last follow-up, and mortality did not significantly favor either group. Intracranial stenting for atherosclerosis did not result in significant benefit over medical treatment.
5.Modified Frailty Index as a Predictor of Postoperative Complications and Patient-Reported Outcomes after Posterior Cervical Decompression and Fusion
Mark James LAMBRECHTS ; Khoa TRAN ; William CONAWAY ; Brian Abedi KARAMIAN ; Karan GOSWAMI ; Sandi LI ; Patrick O'CONNOR ; Parker BRUSH ; Jose CANSECO ; Ian David KAYE ; Barrett WOODS ; Alan HILIBRAND ; Gregory SCHROEDER ; Alexander VACCARO ; Christopher KEPLER
Asian Spine Journal 2023;17(2):313-321
Methods:
Patients undergoing elective PCDF at our urban academic medical center from 2014 to 2020 were included. Patients were categorized by mFI scores (0–0.08, 0.09–0.17, 0.18–0.26, and ≥0.27). Univariate statistics compared demographics, comorbidities, and clinical/surgical outcomes. Multiple linear regression analysis evaluated the magnitude of improvement in PROMs at 1 year.
Results:
A total of 165 patients were included and grouped by mFI scores: 0 (n=36), 0.09 (n=62), 0.18 (n=42), and ≥0.27 (n=30). The severe frailty group (mFI ≥0.27) was significantly more likely to be diabetic (p <0.001) and have a greater Elixhauser comorbidity index (p =0.001). They also had worse baseline Physical Component Score-12 (PCS-12) (p =0.011) and modified Japanese Orthopaedic Association (mJOA) (p =0.012) scores and worse 1-year postoperative PCS-12 (p =0.008) and mJOA (p =0.001) scores. On regression analysis, an mFI score of 0.18 was an independent predictor of greater improvement in ΔVisual Analog Scale neck (β =−2.26, p =0.022) and ΔVAS arm (β =−1.76, p =0.042). Regardless of frailty status, patients had similar 90-day readmission rates (p =0.752), complication rates (p =0.223), and revision rates (p =0.814), but patients with severe frailty were more likely to have longer hospital length of stay (p =0.006) and require non-home discharge (p <0.001).
Conclusions
Similar improvements across most PROMs can be expected irrespective of the frailty status of patients undergoing PCDF. Complication rates, 90-day readmission rates, and revision rates are not significantly different when stratified by frailty status. However, patients with severe frailty are more likely to have longer hospital stays and require non-home discharge.
6.Serotonin Reuptake Inhibitor Increases Pseudarthrosis Rates in Anterior Cervical Discectomy and Fusions
Mark James LAMBRECHTS ; Nicholas D'ANTONIO ; Gregory TOCI ; Brian KARAMIAN ; Josuhu PEZZULO ; Dominic FARRONATO ; Jose CANSECO ; Ian David KAYE ; Barrett WOODS ; Jeffrey RIHN ; Mark KURD ; Joseph LEE ; Alan HILIBRAND ; Christopher KEPLER ; Alexander Richard VACCARO ; Gregory SCHROEDER
Asian Spine Journal 2023;17(2):304-312
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.
7.Effect of Drain Duration and Output on Perioperative Outcomes and Readmissions after Lumbar Spine Surgery
Brian KARAMIAN ; Parth KOTHARI ; Gregory TOCI ; Mark James LAMBRECHTS ; Jose CANSECO ; Jennifer MAO ; Raj NARAYAN ; Samuel ALFONSI ; Francis SIRCH ; Nadim KHEIR ; Nicholas SEMENZA ; Barrett WOODS ; Jeffrey RIHN ; Mark KURD ; Kris RADCLIFF ; Ian David KAYE ; Alan HILIBRAND ; Christopher KEPLER ; Alexander Richard VACCARO ; Gregory SCHROEDER
Asian Spine Journal 2023;17(2):262-271
Methods:
Patients aged ≥18 years who underwent lumbar fusion with a postoperative drain between 2017 and 2020 were included and grouped based on hospital readmission status, last 8-hour drain output (<40 mL cutoff), or drain duration (2 days cutoff). Total output of all drains, total output of the primary drain, drain duration in days, drain output per day, last 8-hour output, penultimate 8-hour output, and last 8-hour delta (last 8-hour output subtracted by penultimate 8-hour output) were collected. Continuous and categorical data were compared between groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis were performed to determine whether drain variables can predict hospital readmission, postoperative blood transfusions, and postoperative anemia. Alpha was 0.05.
Results:
Our cohort consisted of 1,166 patients with 111 (9.5%) hospital readmissions. Results of regression analysis did not identify any of the drain variables as independent predictors of hospital readmission, postoperative blood transfusion, or postoperative anemia. ROC analysis demonstrated the drain variables to be poor predictors of hospital readmission, with the highest area under curve of 0.524 (drain duration), corresponding to a sensitivity of 61.3% and specificity of 49.9%.
Conclusions
Drain output or duration did not affect readmission rates following lumbar spine surgery.
8.A Comparison of Radiographic Alignment between Bilateral and Unilateral Interbody Cages in Patients Undergoing Transforaminal Lumbar Interbody Fusion
Mark James LAMBRECHTS ; Jeremy HEARD ; Nicholas D’ANTONIO ; John BODNAR ; Gregory SCHNEIDER ; Evan BLOOM ; Jose CANSECO ; Barrett WOODS ; Ian David KAYE ; Mark KURD ; Jeffrey RIHN ; Alan HILIBRAND ; Gregory SCHROEDER ; Alexander VACCARO ; Christopher KEPLER
Asian Spine Journal 2023;17(4):666-675
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, p=0.028) and enhanced restoration of segmental lordosis (5.74°±14.1° vs. −1.57°±10.9°, p=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°, p<0.001). Bilateral cage placement was significantly associated with radiographic fusion on bivariate analysis (89.1% vs. 70.3%, p=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; p=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.
9.Incidence, Risk Factors, and Outcomes of Incidental Durotomy during Lumbar Spine Decompression with or without Fusion
Gregory TOCI ; Mark James LAMBRECHTS ; Tariq ISSA ; Brian KARAMIAN ; Nicholas SIEGEL ; Nicholas D’ ANTONIO ; Jose CANSECO ; Mark KURD ; Barrett WOODS ; Ian David KAYE ; Alan HILIBRAND ; Christopher KEPLER ; Alexander VACCARO ; Gregory SCHROEDER
Asian Spine Journal 2023;17(4):647-655
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 (β =2.56, p=0.004). Independent risk factors for incidental durotomies included revisions (odds ratio [OR], 1.73; p<0.001), levels decompressed (OR, 1.11; p=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.
10.Effect of Interbody Composition on the Development of Pseudarthrosis Following Anterior Cervical Discectomy and Fusion
Nicholas D’ANTONIO ; Mark James LAMBRECHTS ; Jeremy HEARD ; Emily BERTIAUME ; Gregory TOCI ; Brian KARAMIAN ; Garrett BREYER ; John BODNAR ; Jose CANSECO ; Alan HILIBRAND ; Gregory SCHROEDER ; Alexander Richard VACCARO ; Christopher KEPLER
Asian Spine Journal 2023;17(3):518-528
Methods:
All patients aged >18 years who underwent primary one- to four-level ACDF at a single institution were retrospectively identified. Propensity matching was performed to compare patients’ PEEK or titanium alloy cages with structural allograft. Multivariate logistic regression analysis was performed to measure the effect of interbody spacer composition on the likelihood of pseudarthrosis development.
Results:
Of the 502 patients who received structural allograft and had 1-year postoperative dynamic radiographs, 96 patients were propensity matched to 32 patients who received a PEEK cage, and 162 patients were propensity matched to 54 patients who received a titanium alloy cage. Multivariate logistic regression analysis identified that PEEK cage implants (odds ratio [OR], 3.34; p =0.007) predicted pseudarthrosis development compared with structural allograft implantation. Titanium alloy cage (OR, 1.64; p =0.156) implantation was not predictive of pseudarthrosis. One-year postoperative PROMs were not significantly different between patients who received PEEK or titanium alloy cages and those who received structural allograft (all p >0.05).
Conclusions
Compared with structural allograft, receiving a PEEK cage increased the risk of pseudarthrosis development following ACDF, whereas receiving a titanium alloy cage had no significant effect on pseudarthrosis development. One-year postoperative patient-reported outcomes were similar between patients who received structural allograft, PEEK, and titanium alloy interbody spacers.

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