Reporting Compliance and Factors Influencing Timeliness of Stroke-Related Trial Results on ClinicalTrials.gov.

Since 2007, research groups are mandated by the Food and Drug Administration Amendments Act (FDAAA) to report clinical trial findings to ClinicalTrials.gov within 12 months of trial completion. This observational study aims to analyze compliance data of stroke-related randomized controlled trials subject to these mandates. Using a previously published algorithm, we identified clinical trials likely to be required to adhere to FDAAA mandates (highly likely applicable clinical trials, or HLACTs) from January 2008 to February 2023. We assessed the proportion of studies that reported results within 12 months of trial completion, as well as those that reported at any point within 5 years. Additionally, we utilized Kaplan-Meier and regression analysis to explore factors associated with on-time reporting. Among 357 stroke-related HLACTs on ClinicalTrials.gov that were terminated or completed between January 1, 2008, and February 1, 2023, 59 (16.5%) reported results within 12 months, while 320 (89.6%) reported results within 5 years. Median reporting times for industry funded, other government or academic institution funded, and National Institute of Health (NIH) funded studies were 18.5 months, 22 months, and 22.5 months, respectively. Open-label studies were less likely to report results by 12 months compared to double-blinded studies (p = 0.002). Biological trials exhibited a lower probability of reporting within 5 years compared to device and/or drug trials (p = 0.007). Clinical trial registries and FDAAA mandates aim to promote accountability and transparency in health sciences research. However, regardless of their funding source, only a minority of stroke-related randomized controlled trials comply with FDAAA's 12-month result reporting mandate.

Surgical vs. Conservative Management of Chronic Sciatica (>3 Months) Due to Lumbar Disc Herniation: Systematic Review and Meta-Analysis.

Sciatica, characterized by leg or back symptoms along the sciatic nerve pathway, often manifests as a chronic condition lasting over 12 weeks. Decision-making between nonoperative treatment and immediate microdiscectomy for chronic sciatica remains challenging, due to the complex relationship between symptom duration, severity, and lumbar discectomy outcomes. In this systematic review, we conducted a comprehensive search across Scopus, PubMed, Web of Science, and the Cochrane Library, identifying relevant two-arm clinical trials up to September 2023. Rigorous screening and data extraction were performed by two independent reviewers, with study quality evaluated using the risk of bias 2 (RoB) tool. This meta-analysis incorporated four studies comprising 352 participants. Our analysis revealed that conservative treatment was associated with a significant reduction in leg pain and improvement in, SF mental, and physical scores compared to surgical intervention. However surgical treatment demonstrated significant improvement in back pain. In conclusion, our findings suggest that surgical intervention may be more effective than non-surgical treatment for chronic sciatica-related back pain. Conservative treatment significantly reduces leg pain while improving mental and physical health outcomes. Ultimately, our findings support conservative as the initial approach unless surgery is warranted, particularly in cases with neurological deficits or cauda equina syndrome.

Bone Quality as Measured by Hounsfield Units More Accurately Predicts Proximal Junctional Kyphosis than Vertebral Bone Quality Following Long-Segment Thoracolumbar Fusion.

OBJECTIVE: To compare the prognostic power of Hounsfield units (HU) and Vertebral Bone Quality (VBQ) score for predicting proximal junctional kyphosis (PJK) following long-segment thoracolumbar fusion to the upper thoracic spine (T1-T6). METHODS: Vertebral bone quality around the upper instrumented vertebrae (UIV) was measured using HU on preoperative CT and VBQ on preoperative MRI. Spinopelvic parameters were also categorized according to the Scoliosis Research Society-Schwab classification. Univariable analysis to identify predictors of the occurrence of PJK and survival analyses with Kaplan-Meier method and Cox regression were performed to identify predictors of time to PJK (defined as ≥10° change in Cobb angle of UIV+2 and UIV). Sensitivity analyses showed thresholds of HU < 164 and VBQ > 2.7 to be most predictive for PJK. RESULTS: Seventy-six patients (mean age 66.0 ± 7.0 years; 27.6% male) were identified, of whom 15 suffered PJK. Significant predictors of PJK were high postoperative pelvic tilt (P = 0.038), high postoperative T1-pelvic angle (P = 0.041), and high postoperative PI-LL mismatch (P = 0.028). On survival analyses, bone quality, as assessed by the average HU of the UIV and UIV+1 was the only significant predictor of time to PJK (odds ratio [OR] 3.053; 95% CI 1.032-9.032; P = 0.044). VBQ measured using the UIV, UIV+1, UIV+2, and UIV-1 vertebrae approached, but did not reach significance (OR 2.913; 95% CI 0.797-10.646; P = 0.106). CONCLUSIONS: In larger cohorts, VBQ may prove to be a significant predictor of PJK following long-segment thoracolumbar fusion. However, Hounsfield units on CT have greater predictive power, suggesting preoperative workup for long-segment thoracolumbar fusion benefits from computed tomography versus magnetic resonance imaging alone to identify those at increased risk of PJK.

Ventriculoperitoneal Shunt Placement Safety in Idiopathic Normal Pressure Hydrocephalus: Anticoagulated Versus Non-Anticoagulated Patients.

BACKGROUND: Many patients with idiopathic normal pressure hydrocephalus (iNPH) have medical comorbidities requiring anticoagulation that could negatively impact outcomes. This study evaluated the safety of ventriculoperitoneal shunt placement in iNPH patients on systemic anticoagulation versus those not on anticoagulation. METHODS: Patients >60 years of age with iNPH who underwent shunting between 2018 and 2022 were retrospectively reviewed. Baseline demographics, comorbidities (quantified by modified frailty index and Charlson comorbidity index), anticoagulant/antiplatelet agent use (other than aspirin), operative details, and complications were collected. Outcomes of interest were the occurrence of postoperative hemorrhage and overdrainage. RESULTS: A total of 234 patients were included in the study (mean age 75.22 ± 6.04 years; 66.7% male); 36 were on anticoagulation/antiplatelet therapy (excluding aspirin). This included 6 on Warfarin, 19 on direct Xa inhibitors, 10 on Clopidogrel, and 1 on both Clopidogrel and Warfarin. Notably, 70% of patients (164/234) used aspirin alone or combined with anticoagulation or clopidogrel. Baseline modified frailty index was similar between groups, but those on anticoagulant/antiplatelet therapy had a higher mean Charlson comorbidity index (2.67 ± 1.87 vs. 1.75 ± 1.84; P = 0.001). Patients on anticoagulants were more likely to experience tract hemorrhage (11.1 vs. 2.5%; P = 0.03), with no significant difference in the rates of intraventricular hemorrhage or overdrainage-related subdural fluid collection. CONCLUSIONS: Anticoagulant and antiplatelet agents are common in the iNPH population, and patients on these agents experienced higher rates of tract hemorrhage following ventriculoperitoneal shunt placement; however, overall hemorrhagic complication rates were similar.

Injectable bioactive poly(propylene fumarate) and polycaprolactone based click chemistry bone cement for spinal fusion in rabbits.

Degenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano-hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano-hydroxyapatite (nHA) and the released rhBMP-2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.

Significant Reduction in Bone Density as Measured by Hounsfield Units in Patients with Ankylosing Spondylitis or Diffuse Idiopathic Skeletal Hyperostosis.

Background: Multisegmental pathologic autofusion occurs in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). It may lead to reduced vertebral bone density due to stress shielding. Methods: This study aimed to determine the effects of autofusion on bone density by measuring Hounsfield units (HU) in the mobile and immobile spinal segments of patients with AS and DISH treated at a tertiary care center. The mean HU was calculated for five distinct regions-cranial adjacent mobile segment, cranial fused segment, mid-construct fused segment, caudal fused segment, and caudal adjacent mobile segment. Means for each region were compared using paired-sample t-tests. Multivariable regression was used to determine independent predictors of mid-fused segment HUs. Results: One hundred patients were included (mean age 76 ± 11 years, 74% male). The mean HU for the mid-construct fused segment (100, 95% CI [86, 113]) was significantly lower than both cranial and caudal fused segments (174 and 108, respectively; both p < 0.001), and cranial and caudal adjacent mobile segments (195 and 115, respectively; both p < 0.001). Multivariable regression showed the mid-construct HUs were predicted by history of smoking (-30 HU, p = 0.009). Conclusions: HUs were significantly reduced in the middle of long-segment autofusion, which was consistent with stress shielding. Such shielding may contribute to the diminution of vertebral bone integrity in AS/DISH patients and potentially increased fracture risk.

Bioactive Moldable Click Chemistry Polymer Cement with Nano-Hydroxyapatite and Growth Factor-Enhanced Posterolateral Spinal Fusion in a Rabbit Model.

Spinal injuries or diseases necessitate effective fusion solutions, and common clinical approaches involve autografts, allografts, and various bone matrix products, each with limitations. To address these challenges, we developed an innovative moldable click chemistry polymer cement that can be shaped by hand and self-cross-linked in situ for spinal fusion. This self-cross-linking cement, enabled by the bioorthogonal click reaction, excludes the need for toxic initiators or external energy sources. The bioactivity of the cement was promoted by incorporating nanohydroxyapatite and microspheres loaded with recombinant human bone morphogenetic protein-2 and vascular endothelial growth factor, fostering vascular induction and osteointegration. The release kinetics of growth factors, mechanical properties of the cement, and the ability of the scaffold to support in vitro cell proliferation and differentiation were evaluated. In a rabbit posterolateral spinal fusion model, the moldable cement exhibited remarkable induction of bone regeneration and effective bridging of spine vertebral bodies. This bioactive moldable click polymer cement therefore presents a promising biomaterial for spinal fusion augmentation, offering advantages in safety, ease of application, and enhanced bone regrowth.

Biodegradable poly(caprolactone fumarate) 3D printed scaffolds for segmental bone defects within the Masquelet technique.

Segmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one-stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4-week implantation study. Histological analysis, including tissue staining and immunohistochemistry with bone-specific antibodies, was conducted for histomorphometry evaluation. The PCLF/PCL spacers demonstrated compressive properties within 6 ± 0.5 MPa (strength) and 140 ± 15 MPa (modulus). Both porous PCLF/PCL and Nonporous PMMA formed collagen-rich membranes (PCLF/PCL: 92% ± 1.3%, PMMA: 86% ± 1.5%) similar to those induced in the Masquelet technique, indicating PCLF/PCL's potential for one-stage healing. Immunohistochemistry confirmed biomarkers for tissue regeneration, underscoring PCLF/PCL's regenerative capabilities. This research highlights PCLF/PCL scaffolds' ability to induce membrane formation in critical-sized segmental bone defects, supporting their use in one-stage surgery. Both solid and porous PCLF/PCL spacers showed adequate compressive properties, with the porous variants exhibiting BMP-2 expression and woven bone formation, akin to clinical standard PMMA. Notably, the early ossification of the membrane into the pores of porous scaffolds suggests potential for bone interlocking and regeneration, potentially eliminating the need for a second surgery required for PMMA spacers. The biocompatibility and biodegradability of PCLF/PCL make them promising alternatives for treating critical bone defects, especially in vulnerable patient groups.

Reduced Bone Density Based on Hounsfield Units After Long-Segment Spinal Fusion with Harrington Rods.

BACKGROUND: Long-segment instrumentation, such as Harrington rods, offloads vertebrae within the construct, which may result in significant stress shielding of the fused segments. The present study aimed to determine the effects of spinal fusion on bone density by measuring Hounsfield units (HUs) throughout the spine in patients with a history of Harrington rod fusion. METHODS: Patients with a history of Harrington rod fusion treated at a single academic institution were identified. Mean HUs were calculated at 5 spinal segments for each patient: cranial adjacent mobile segment, cranial fused segment, midconstruct fused segment, caudal fused segment, and caudal adjacent mobile segment. Mean HUs for each level were compared using a paired-sample t test, with statistical significance defined by P < 0.05. Hierarchic multiple regression, including age, gender, body mass index, and time since original fusion, was used to determine predictors of midfused segment HUs. RESULTS: One hundred patients were included (mean age, 55 ± 12 years; 62% female). Mean HUs for the midconstruct fused segment (110; 95% confidence interval [CI], 100-121) were significantly lower than both the cranial and caudal fused segments (150 and 118, respectively; both P < 0.05), as well as both the cranial and caudal adjacent mobile segments (210 and 130, respectively; both P < 0.001). Multivariable regression showed midconstruct HUs were predicted only by patient age (-2.6 HU/year; 95% CI, -3.4 to -1.9; P < 0.001) and time since original surgery (-1.4 HU/year; 95% CI, -2.6 to -0.2; P = 0.02). CONCLUSIONS: HUs were significantly decreased in the middle of previous long-segment fusion constructs, suggesting that multilevel fusion constructs lead to vertebral bone density loss within the construct, potentially from stress shielding.

The Predictors of Incidental Durotomy in Patients Undergoing Pedicle Subtraction Osteotomy for the Correction of Adult Spinal Deformity.

Background: Pedicle subtraction osteotomy (PSO) is a powerful tool for sagittal plane correction in patients with rigid adult spinal deformity (ASD); however, it is associated with high intraoperative blood loss and the increased risk of durotomy. The objective of the present study was to identify intraoperative techniques and baseline patient factors capable of predicting intraoperative durotomy. Methods: A tri-institutional database was retrospectively queried for all patients who underwent PSO for ASD. Data on baseline comorbidities, surgical history, surgeon characteristics and intraoperative maneuvers were gathered. PSO aggressiveness was defined as conventional (Schwab 3 PSO) or an extended PSO (Schwab type 4). The primary outcome of the study was the occurrence of durotomy intraoperatively. Univariable analyses were performed with Mann-Whitney U tests, Chi-squared analyses, and Fisher's exact tests. Statistical significance was defined by p < 0.05. Results: One hundred and sixteen patients were identified (mean age 61.9 ± 12.6 yr; 44.8% male), of whom 51 (44.0%) experienced intraoperative durotomy. There were no significant differences in baseline comorbidities between those who did and did not experience durotomy, with the exception that baseline weight and body mass index were higher in patients who did not suffer durotomy. Prior surgery (OR 2.73; 95% CI [1.13, 6.58]; p = 0.03) and, more specifically, prior decompression at the PSO level (OR 4.23; 95% CI [1.92, 9.34]; p < 0.001) was predictive of durotomy. A comparison of surgeon training showed no statistically significant difference in durotomy rate between fellowship and non-fellowship trained surgeons, or between orthopedic surgeons and neurosurgeons. The PSO level, PSO aggressiveness, the presence of stenosis at the PSO level, nor the surgical instrument used predicted the odds of durotomy occurrence. Those experiencing durotomy had similar hospitalization durations, rates of reoperation and rates of nonroutine discharge. Conclusions: In this large multisite series, a history of prior decompression at the PSO level was associated with a four-fold increase in intraoperative durotomy risk. Notably the use of extended (versus) standard PSO, surgical technique, nor baseline patient characteristics predicted durotomy. Durotomies occurred in 44% of patients and may prolong operative times. Additional prospective investigations are merited.

Opportunistic CT-Based Hounsfield Units Strongly Correlate with Biomechanical CT Measurements in the Thoracolumbar Spine.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Hounsfield units (HUs) are known to correlate with clinical outcomes, no study has evaluated how they correlate with BCT and DXA measurements. SUMMARY OF BACKGROUND: Low bone mineral density (BMD) represents a major risk factor for fracture and poor outcomes following spine surgery. Dual-energy x-ray absorptiometry (DXA) can provide regional BMD measurements but has limitations. Opportunistic HUs provide targeted BMD estimates; however, they are not formally accepted for diagnosing osteoporosis in current guidelines. More recently, biomechanical computed tomography (BCT) analysis has emerged as a new modality endorsed by the International Society for Clinical Densitometry (ISCD) for assessing bone strength. METHODS: Consecutive cases from 2017-2022 at a single institution were reviewed for patients who underwent BCT in the thoracolumbar spine. BCT-measured vertebral strength, trabecular BMD, and the corresponding American College of Radiology (ACR) Classification were recorded. DXA studies within three months of the BCT were reviewed. Pearson Correlation Coefficients were calculated, and receiver-operating characteristic curves were constructed to assess the predictive capacity of HUs. Threshold analysis was performed to identify optimal HU values for identifying osteoporosis and low BMD. RESULTS: Correlation analysis of 114 cases revealed a strong relationship between HUs and BCT vertebral strength (r=0.69; P<0.0001; R2=0.47) and trabecular BMD (r=0.76; P<0.0001; R2=0.58). However, DXA poorly correlated with opportunistic HUs and BCT measurements. HUs accurately predicted osteoporosis and low BMD (Osteoporosis: C=0.95, 95% CI 0.89-1.00; Low BMD: C=0.87, 95% CI 0.79-0.96). Threshold analysis revealed that 106 and 122 HUs represent optimal thresholds for detecting osteoporosis and low BMD. CONCLUSION: Opportunistic HUs strongly correlated with BCT-based measures, while neither correlated strongly with DXA-based BMD measures in the thoracolumbar spine. HUs are easy to perform at no additional cost and provide accurate BMD estimates at non-instrumented vertebral levels across all ACR-designated BMD categories.