Drug Administration Investigational Device Exemption Research Articles

Pulsed Field Ablation to Treat Paroxysmal Atrial Fibrillation: Safety and Effectiveness in the AdmIRE Pivotal Trial.

Evidence from clinical trials of early pulsed field ablation (PFA) systems in treating atrial fibrillation has demonstrated their promising potential to reduce complications associated with conventional thermal modalities while maintaining efficacy. However, the lack of a fully integrated mapping system, a staple technology of most modern electrophysiology procedures, poses limitations in lesion creation and workflow options. A novel variable-loop PFA catheter integrated with an electroanatomic mapping system has been developed that allows for real-time nonfluoroscopic procedural guidance and lesion indexing as well as feedback of tissue-to-catheter proximity. AdmIRE (Assessment of Safety and Effectiveness in Treatment Management of Atrial Fibrillation With the Bosense-Webster Irreversible Electroporation Ablation System), a multicenter, single-arm, Food and Drug Administration investigational device exemption study, evaluated the long-term safety and effectiveness of this integrated PFA system in a large United States-based drug-refractory symptomatic paroxysmal atrial fibrillation patient population. Using the PFA catheter with a compatible electroanatomic mapping system, patients with drug-refractory symptomatic paroxysmal atrial fibrillation underwent pulmonary vein isolation. The primary safety end point was primary adverse event within 7 days of ablation. The primary effectiveness end point was a composite end point that included 12-month freedom from documented atrial tachyarrhythmia (ie, atrial fibrillation, atrial tachycardia, atrial flutter) episodes, failure to achieve pulmonary vein isolation, use of a nonstudy catheter for pulmonary vein isolation, repeat procedure (except for one redo during blanking), taking a new or previously failed class I or III antiarrhythmic drug at higher dose after blanking, or direct current cardioversion after blanking. At 30 centers, 277 patients with paroxysmal atrial fibrillation (61.5±10.3 years of age; 64.3% male) in the pivotal cohort underwent PFA. More than 25% of the procedures were performed without fluoroscopy. Median (Q1, Q3) pulmonary vein isolation procedure, fluoroscopy, and transpired PFA application times were 81.0 (61.0, 112.0), 7.1 (0.00, 14.3), and 31.0 (24.8, 40.9) minutes, respectively. The primary adverse event rate was 2.9% (8 of 272), with the most common complication being pericardial tamponade. The 12-month primary effectiveness end point was 74.6%. The 1-year freedom from atrial fibrillation, atrial tachycardia, or atrial flutter recurrence rate after blanking was 75.4%. Substantial improvements in quality of life were observed as early as 3 months after the procedure, concurrent with a reduction in multiple health care use measures. AdmIRE confirmed the safety and effectiveness of the variable-loop PFA catheter, with short procedure and PFA application times and low fluoroscopy exposure. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05293639.

Five-year Follow-up of a Prospective Food and Drug Administration Investigational Device Exemption Trial Evaluating a PEEK-on-Ceramic Cervical Disc Replacement.

Prospective trial comparing the investigation group to propensity matched historic control group. To evaluate 5-year results of single-level PEEK-on-ceramic cervical total disc replacement (TDR) compared to a propensity matched anterior cervical discectomy and fusion (ACDF) control group. Cervical TDR has gained acceptance as treatment for symptomatic disc degeneration. The design and materials used in these devices continue to evolve. Data were collected in the Food and Drug Administration Investigational Device Exemption trial for the PEEK-on-ceramic Simplify(®) Cervical Artificial Disc (n=150) with comparison to a propensity matched ACDF control group (n=117). All patients were treated for single-level cervical disc degeneration with radiculopathy and/or myelopathy. Clinical outcome was based on composite clinical success (CCS), Neck Disability Index (NDI), visual analog scales (VAS) assessing pain, re-operations, and satisfaction. Radiographic measures included segmental range of motion (ROM), disc space height, and heterotopic ossification (HO). Evaluations were performed pre-operatively and post-operatively within 2 and 6 weeks, and 3, 6, 12 months, and annually thereafter. At 5-year follow-up, CCS was significantly greater with TDR than ACDF (91.1% vs. 74.6%; P<0.01). In the TDR group, the mean NDI score was 63.3 pre-operatively, reduced significantly to 23.1 at 6 weeks and remained below 20 throughout 5-year follow-up. In the ACDF group, the mean pre-operative NDI score was 62.4, decreasing to 33.7 at 6 weeks, and ranged from 25.9 to 21.5 throughout follow-up. Mean NDI scores were significantly lower in TDR group at all post-operative points (P<0.05). Mean TDR ROM was 7.3o pre-operatively and 10.1o at 5 years. Bridging HO occurred in 9%. With TDR, there were 6 re-operations (4.0%) vs. 11 (9.4%) with ACDF (P>0.40). PEEK-on-ceramic TDR produced significantly improved outcomes maintained throughout 5-year follow-up, were similar or superior to ACDF, supporting TDR in appropriately selected patients.

Lumbar Facet Arthroplasty Versus Fusion for Grade-I Degenerative Spondylolisthesis with Stenosis: A Prospective Randomized Controlled Trial.

The comparative effectiveness of decompression plus lumbar facet arthroplasty versus decompression plus instrumented lumbar spinal fusion in patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis is unknown. In this randomized, controlled, Food and Drug Administration Investigational Device Exemption trial, we assigned patients who had single-level lumbar spinal stenosis and grade-I degenerative spondylolisthesis to undergo decompression plus lumbar facet arthroplasty (arthroplasty group) or decompression plus fusion (fusion group). The primary outcome was a predetermined composite clinical success score. Secondary outcomes included the Oswestry Disability Index (ODI), visual analog scale (VAS) back and leg pain, Zurich Claudication Questionnaire (ZCQ), Short Form (SF)-12, radiographic parameters, surgical variables, and complications. A total of 321 adult patients were randomized in a 2:1 fashion, with 219 patients assigned to undergo facet arthroplasty and 102 patients assigned to undergo fusion. Of these, 113 patients (51.6%) in the arthroplasty group and 47 (46.1%) in the fusion group who had either reached 24 months of postoperative follow-up or were deemed early clinical failures were included in the primary outcome analysis. The arthroplasty group had a higher proportion of patients who achieved composite clinical success than did the fusion group (73.5% versus 25.5%; p < 0.001), equating to a between-group difference of 47.9% (95% confidence interval, 33.0% to 62.8%). The arthroplasty group outperformed the fusion group in most patient-reported outcome measures (including the ODI, VAS back pain, and all ZCQ component scores) at 24 months postoperatively. There were no significant differences between groups in surgical variables or complications, except that the fusion group had a higher rate of developing symptomatic adjacent segment degeneration. Among patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis, lumbar facet arthroplasty was associated with a higher rate of composite clinical success than fusion was at 24 months postoperatively. Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Prosthesis design and likelihood of achieving physiological range of motion after cervical disc arthroplasty: analysis of range of motion data from 1,173 patients from 7 IDE clinical trials

BACKGROUND CONTEXTThe functional goals of cervical disc arthroplasty (CDA) are to restore enough range of motion (ROM) to reduce the risk of accelerated adjacent segment degeneration but limit excessive motion to maintain a biomechanically stable index segment. This motion-range is termed the “Physiological mobility range.” Clinical studies report postoperative ROM averaged over all study subjects but they do not report what proportion of reconstructed segments yield ROM in the Physiological mobility range following CDA surgery. PURPOSETo calculate the proportion of reconstructed segments that yield flexion-extension ROM (FE-ROM) in the Physiological mobility range (defined as 5°-16°) by analyzing the 24-month postoperative data reported by clinical trials of various cervical disc prostheses. STUDY DESIGN/SETTINGAnalysis of 24-month postoperative FE-ROM data from clinical trials. PATIENT SAMPLEData from 1,173 patients from single-level disc replacement clinical trials of 7 cervical disc prostheses. OUTCOME MEASURES24-month postoperative index-level FE-ROM. METHODSThe FE-ROM histograms reported in Food and Drug Administration-Investigational Device Exemption (FDA-IDE) submissions and available for this analysis were used to calculate the frequencies of implanted levels with postoperative FE-ROM in the following motion-ranges: Hypomobile (0°–4°), Physiological (5°–16°), and Hypermobile (≥17°). The ROM histograms also allowed calculation of the average ROM of implanted segments in each of the 3 motion-ranges. RESULTSOnly 762 of 1,173 patients (implanted levels) yielded 24-month postCDA FE-ROM in the physiological mobility range (5°–16°). The proportions ranged from 60% to 79% across the 7 disc-prostheses, with an average of 65.0%±6.2%. Three-hundred and two (302) of 1,173 implanted levels yielded ROM in the 0°–4° range. The proportions ranged from 15% to 38% with an average of 25.7%±8.9%. One-hundred and nine (109) of 1,173 implanted levels yielded ROM of ≥17° with a range of 2%-21% and an average proportion of 9.3%±7.9%. The prosthesis with built-in stiffness due to its nucleus-annulus design yielded the highest proportion (103/131, 79%) of implanted segments in the physiological mobility range, compared to the cohort average of 65% (p<.01). Sixty-five of the 350 (18.6%) discs implanted with the 2 mobile-core designs in this cohort yielded ROM≥17° as compared to the cohort average of 9.3% (109/1,173) (p<.05). At 2-year postCDA, the “hypomobile” segments moved on average 2.4±1.2°, those in the “physiological-mobility” group moved 9.4±3.2°, and the hypermobile segments moved 19.6±2.6°. CONCLUSIONSProsthesis design significantly influenced the likelihood of achieving FE-ROM in the physiological mobility range, while avoiding hypomobility or hypermobility (p<.01). Postoperative ROM averaged over all study subjects provides incomplete information about the prosthesis performance - it does not tell us how many implanted segments achieve physiological mobility and how many end up with hypomobility or hypermobility. We conclude that the proportion of index levels achieving postCDA motions in the physiological mobility range (5°–16°) is a more useful outcome measure for future clinical trials.

Comparative Safety of Pulsed Field Ablation and Cryoballoon Ablation Technologies for Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation: A Critical Literature Review and Indirect Treatment Comparison.

Cryoballoon ablation (CBA) is a standard catheter ablation technology with demonstrated clinical effectiveness for the treatment of paroxysmal atrial fibrillation (PAF); however, it can be associated with major adverse events, including phrenic nerve paralysis. Pulsed field ablation (PFA) is a novel, minimally thermal technology with comparable effectiveness and low safety risk. This study aimed to compare the safety profiles of PFA and CBA through critical analyses of the literature and indirect treatment comparisons. Studies were identified by searching the MEDLINE database and the Clinicaltrials.gov registry. Registered clinical trials and/or Food and Drug Administration Investigation Device Exemption (FDA IDE) studies evaluating PFA or CBA in adult patients with drug-refractory PAF between January 2008 and March 2023 were selected. Comparative safety between PFA and CBA was assessed for major and prespecified adverse events. Indirect comparisons were conducted using the proportion of patients experiencing adverse events and confirmed with single-arm meta-analyses and sensitivity analyses. Data were extracted from three PFA publications including a total of 497 patients and six CBA studies including a total of 1113 patients. The analysis revealed that PFA was associated with significantly lower risk of major adverse events {risk difference-4.3% [95% confidence interval (CI)-5.8,-2.8]; risk ratio 0.16 [95% CI 0.07, 0.45]} and prespecified adverse events [risk difference -2.5% (95% CI-4.4,-0.5); risk ratio 0.53 (95% CI 0.31, 0.96)]. Meta-analyses confirmed the lower rate of major adverse events for PFA [0.4% (95% CI 0.0, 1.3)] vs. CBA [5.6% (95% CI 2.6, 8.6)] and prespecified adverse events for PFA [2.7% (95% CI 1.2, 4.1)] vs. CBA [5.8% (95% CI 2.7, 9.0)]. Sensitivity analyses exploring heterogeneity across studies confirmed robustness of the main analyses. The findings of this study show that PFA has a more favorable safety profile than CBA, with significantly lower risks of major and prespecified adverse events. These indirect comparisons help contextualize the safety of PFA compared to CBA for the treatment of drug-refractory PAF in the absence of head-to-head studies.

EsophAguS Deviation During RadiofrequencY Ablation of Atrial Fibrillation: The EASY AF Trial

BackgroundInjury to the esophagus has been reported in a high percentage of patients undergoing ablation of atrial fibrillation (AF). ObjectivesThis study assessed the incidence of esophageal injury in patients undergoing ablation of AF with and without an esophageal deviating device. MethodsThis prospective, randomized, multicenter, double-blinded, controlled Food and Drug Administration investigational device exemption trial compared the incidence of ablation-related esophageal lesions, as assessed by endoscopy, in patients undergoing AF ablation assigned to a control group (luminal esophageal temperature [LET] monitoring alone) compared with patients randomized to a deviation group (esophagus deviation device + LET). This novel deviating device uses vacuum suction and mechanical deflection to deviate a segment of the esophagus, including the trailing edge. ResultsThe data safety and monitoring board recommended stopping the study early after randomizing 120 patients due to deviating device efficacy. The primary study endpoint, ablation injury to the esophageal mucosa, was significantly less in the deviation group (5.7%) in comparison to the control group (35.4%; P < 0.0001). Control patients had a significantly higher severity and greater number of ablation lesions per patient. There was no adverse event assigned to the device. By multivariable analysis, the only feature associated with reduced esophageal lesions was randomization to deviating device (OR: 0.13; 95% CI: 0.04-0.46; P = 0.001). Among control subjects, there was no difference in esophageal lesions with high power/short duration (31.8%) vs other radiofrequency techniques (37.2%; P = 0.79). ConclusionsThe use of an esophageal deviating device resulted in a significant reduction in ablation-related esophageal lesions without any adverse events.

Current and Expanded Indications for Cervical Disc Arthroplasty: Beyond the FDA IDE Studies.

The widespread success of cervical disc arthroplasty (CDA) has led to an interest in expanding indications beyond those outlined in the initial Food and Drug Administration investigational device exemption studies. Some of these off-label indications currently include 3-level and 4-level CDA, hybrid constructs with adjacent segment anterior cervical discectomy and fusion or corpectomy constructs, pre-existing kyphosis, revision of a failed anterior cervical discectomy and fusion to a CDA, CDA in the setting of significant degenerative disc disease and/or facet joint arthropathy, CDA for congenital cervical stenosis, and CDA in the presence of ossification of the posterior longitudinal ligament. This review article will summarize the current literature pertaining to the aforementioned indications.

499 Prospective, Randomized and Controlled Multicenter Study of Posterior Lumbar Facet Arthroplasty for the Treatment of Spondylolisthesis

INTRODUCTION: Prospective, Randomized and Controlled Multicenter Study of Posterior Lumbar Facet Arthroplasty for the Treatment of Spondylolisthesis. METHODS: The study was a prospective, randomized, controlled Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial evaluating the investigational TOPS device to the control, transforaminal interbody fusion (TLIF) and pedicle screw fixation. Follow-up duration was a minimum twenty-four months. RESULTS: A total of 249 patients were evaluated comparing the investigational TOPS group (n = 170) to the control TLIF group (n = 79. There were no statistically significant differences between implanted levels (L4-5 TOPS 95%; L4-5 TLIF 95%) or blood loss. The overall composite measure for clinical success was statistically significantly higher in the TOPS group, 85%, compared to the fusion group, 64% (p = 0.0138). The percentage of subjects reporting minimum 15-point improvement in ODI showed a statistically significant difference (p-value = 0.037) favoring TOPS (94.0%) over TLIF (79.4%). CONCLUSIONS: This study demonstrates that posterior lumbar decompression and dynamic stabilization with the TOPS device is safe and efficacious in the treatment of lumbar stenosis with degenerative spondylolisthesis. Additionally, decompression and dynamic stabilization with the TOPS device maintains segmental motion.

Cervical Disk Arthroplasty and Range of Motion at 7 Years: Impact on Adjacent Level Degeneration.

Secondary analysis of data collected in a prospective, randomized, noninferiority Food and Drug Administration (FDA) Investigational Device Exemption (IDE) clinical trial. The objective of this study was to evaluate the impact of range of motion (ROM) following single-level cervical disk arthroplasty (CDA) on the development of radiographic adjacent level degeneration (ALD). The rationale for CDA is that maintenance of index-level ROM will decrease adjacent level stresses and ultimately reduce the development of ALD compared with anterior cervical discectomy and fusion. However, little information is available on the impact of hypermobility on the development of ALD after CDA. Radiographic assessments were evaluated for index-level flexion-extension ROM and ALD. Continuous data was assessed using 1-way analysis of variance. The relationship between ALD progression and ROM was evaluated using χ 2 tests. The α was set at 0.05. More ALD progression was observed after anterior cervical discectomy and fusion than CDA ( P =0.002 at the superior and P =0.049 at the inferior level). Furthermore, there was an association between ALD progression and ROM ( P =0.014 at the superior level and P =0.050 at the inferior level) where patients with mid-ROM after CDA experienced the lowest frequency of ALD progression at the superior and inferior levels. Patients with the lowest and highest ROM after CDA experienced a greater increase in ALD score at the inferior level ( P =0.046). Sex and age were associated with ROM groups ( P =0.001 and 0.023, respectively). While maintenance of index-level ROM is protective after CDA, patients with the highest ROM after CDA have similar rates of ALD progression to the lowest ROM and greater increases in ALD compared with mid-ROM after CDA. High ROM after CDA may contribute to ALD progression.

A Prospective Study of Lumbar Facet Arthroplasty in the Treatment of Degenerative Spondylolisthesis and Stenosis: Results from the Total Posterior Spine System (TOPS) IDE Study.

Prospective randomized Food and Drug Administration investigational device exemption clinical trial. The purpose of the present study is to report the 1-year clinical and radiographic outcomes and safety profile of patients who underwent lumbar facet arthroplasty through implantation of the Total Posterior Spine System (TOPS) device. Lumbar facet arthroplasty is one proposed method of dynamic stabilization to treat grade-1 spondylolisthesis with stenosis; however, there are currently no Food and Drug Administration-approved devices for facet arthroplasty. Standard demographic information was collected for each patient. Radiographic parameters and patient-reported outcome measures were assessed preoperatively and at regular postoperative intervals. Complication and reoperation data were also collected for each patient. At the time of this study, 153 patients had undergone implantation of the TOPS device. The mean surgical time was 187.8 minutes and the mean estimated blood loss was 205.7cc. The mean length of hospital stay was 3.0 days. Mean Oswestry Disability Index, Visual Analog Score leg and back, and Zurich Claudication Questionnaire scores improved significantly at all postoperative time points ( P >0.001). There were no clinically significant changes in radiographic parameters, and all operative segments remained mobile at 1-year follow-up. Postoperative complications occurred in 11 patients out of the 153 patients (7.2%) who underwent implantation of the TOPS device. Nine patients (5.9%) underwent a total of 13 reoperations, 1 (0.6%) of which was for device-related failure owing to bilateral L5 pedicle screw loosening. Lumbar facet arthroplasty with the TOPS device demonstrated a statistically significant improvement in all patient-reported outcome measures and the ability to maintain motion at the index level while limiting sagittal translation with a low complication rate.

Effect of epidural spinal cord stimulation after chronic spinal cord injury on volitional movement and cardiovascular function: study protocol for the phase II open label controlled E-STAND trial

IntroductionSpinal cord injury (SCI) leads to significant changes in morbidity, mortality and quality of life (QOL). Currently, there are no effective therapies to restore function after chronic SCI. Preliminary studies...

Feasibility of a Combined Neuromodulation and Yoga Intervention for Mild Traumatic Brain Injury and Chronic Pain: Protocol for an Open-label Pilot Trial.

BackgroundMild traumatic brain injury (mTBI) and chronic pain often co-occur and worsen rehabilitation outcomes. There is a need for improved multimodal nonpharmacologic treatments that could improve outcomes for both conditions. Yoga is a promising activity-based intervention for mTBI and chronic pain, and neuromodulation through transcranial magnetic stimulation is a promising noninvasive, nonpharmacological treatment for mTBI and chronic pain. Intermittent theta burst stimulation (iTBS) is a type of patterned, excitatory transcranial magnetic stimulation. iTBS can induce a window of neuroplasticity, making it ideally suited to boost the effects of treatments provided after it. Thus, iTBS may magnify the impacts of subsequently delivered interventions as compared to delivering those interventions alone and accordingly boost their impact on outcomes.ObjectiveThe aim of this study is to (1) develop a combined iTBS+yoga intervention for mTBI and chronic pain, (2) assess the intervention’s feasibility and acceptability, and (3) gather preliminary clinical outcome data on quality of life, function, and pain that will guide future studies.MethodsThis is a mixed methods, pilot, open-labeled, within-subject intervention study. We will enroll 20 US military veteran participants. The combined iTBS+yoga intervention will be provided in small group settings once a week for 6 weeks. The yoga intervention will follow the LoveYourBrain yoga protocol—specifically developed for individuals with TBI. iTBS will be administered immediately prior to the LoveYourBrain yoga session. We will collect preliminary quantitative outcome data before and after the intervention related to quality of life (TBI-quality of life), function (Mayo-Portland Adaptability Index), and pain (Brief Pain Inventory) to inform larger studies. We will collect qualitative data via semistructured interviews focused on intervention acceptability after completion of the intervention.ResultsThis study protocol was approved by Edward Hines Jr Veterans Administration Hospital Institutional Review Board (Hines IRB 1573116-4) and was prospectively registered on ClinicalTrials.gov (NCT04517604). This study includes a Food and Drug Administration Investigational Device Exemption (IDE: G200195). A 2-year research plan timeline was developed. As of March 2022, a total of 6 veterans have enrolled in the study. Data collection is ongoing and will be completed by November 2022. We expect the results of this study to be available by October 2024.ConclusionsWe will be able to provide preliminary evidence of safety, feasibility, and acceptability of a novel combined iTBS and yoga intervention for mTBI and chronic pain—conditions with unmet treatment needs.Trial RegistrationClinicalTrials.gov NCT04517604; https://www.clinicaltrials.gov/ct2/show/NCT04517604International Registered Report Identifier (IRRID)DERR1-10.2196/37836

Intervertebral Disk Health Following Vertebral Body Tethering for Adolescent Idiopathic Scoliosis: A Preliminary Study.

Interest in vertebral body tethering (VBT) as an alternative to posterior spinal fusion for adolescent idiopathic scoliosis (AIS) continues to grow. The purpose of this study was to prospectively assess intervertebral disk health on magnetic resonance imaging (MRI) at 1 year following VBT in AIS patients. AIS patients were enrolled in a prospective surgeon-sponsored Food and Drug Administration (FDA) Investigational Device Exemption (IDE) Study and underwent MRI at 1-year following VBT. All spanned disks and the untethered disks immediately adjacent to the upper instrumented vertebra and lowest instrumented vertebra levels were evaluated according to Pfirrmann grading criteria. Associations between patient factors and preoperative and postoperative disk health and patient-reported outcomes were evaluated. Twenty-two patients were enrolled with a postoperative MRI (25 curves, 188 disks), and 7 patients (7 curves) had both preoperative and postoperative MRIs (67 disks). The mean age was 12.7 years. Most were Risser 0 (65%) and either Sanders Skeletal Maturity Score 3 (35%) or 4 (53%). In the 7 patients with preoperative and postoperative MRI, the mean Pfirrmann grade of the disks spanned by the tether was 1.88 preoperatively and 2.31 postoperatively ( P =0.0075). No statistically significant differences in preoperative versus postoperative Pfirrmann grade were identified in the disks adjacent to the upper or lower instrumented vertebrae. No association was found between patient-reported outcomes and Pfirrmann grade. At 1 year postoperatively, increased degenerative changes in disks spanned by the tether was identifiable on MRI without evidence of adjacent segment disk disease. These changes were not associated with patient-reported outcomes. Level III.

Myopic Shift at 10-Year Follow-up in the Infant Aphakia Treatment Study

We studied the myopic shift and anisometropia at 10.6 (+/-0.3) years of age in the Infant Aphakia Treatment Study. We found myopic shift continues in the operated eye from 5-10.5 years at a lower rate than that prior to age five years while anisometropia increases proportionally. The Infant Aphakia Treatment Study (IATS) is a randomized clinical trial initially designed to compare outcomes in infants under seven months of age who underwent primary implantation of an intraocular lens (IOL) versus being left aphakic and receiving a contact lens correction following cataract surgery in infancy.1 Patients were enrolled from 2004 through 2009 with the last 10-year follow-up exam completed in 2019. The study design was approved by the institutional review boards of the 12 participating sites and followed the tenets of the Declaration of Helsinki. The off-label use of the AcrySof SN60AT and MA60AC IOLs (Alcon Laboratories, Fort Worth Tx.) was covered under the United States Food and Drug Administration investigational device exemption. The trial is registered at www.ClinicalTrials.gov (identifier, NCT00212134).

Prospective Pilot Study of Robotic-Assisted Harvest of the Latissimus Dorsi Muscle: A 510(k) Approval Study with U.S. Food and Drug Administration Investigational Device Exemption.

There are no U.S. Food and Drug Administration (FDA)-approved indications for robotic plastic surgery. This study was designed to demonstrate safety and efficacy of the robotic latissimus dorsi harvest for FDA approval. This prospective, single-arm study was conducted under an investigational device exemption through the FDA for obtaining 510(k) approval. The primary safety endpoint was adverse events attributable to harvest. Primary efficacy endpoints included muscle viability after harvest and conversion to open technique. Secondary endpoints included postoperative pain and upper extremity function. Fifteen patients enrolled, with a mean age of 50 ± 10 years and a mean body mass index of 25 ± 4 kg/m2. There were no adverse events, all muscles were viable after harvest, and there were zero conversions to open procedures. Visual analogue scale scores for pain progressively decreased postoperatively and returned to baseline, indicating resolution of postoperative pain. Physical therapy assessment demonstrated recovery of function in all range-of-movement domains by 36 weeks. There was no difference in function of the operated extremity between baseline and 36 weeks' follow-up for Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire (p = 0.87); QuickDASH Work Module (p > 0.05); and QuickDASH Sports Module (p > 0.05). The use of the da Vinci Robotic Surgical System is safe based on zero adverse events attributable to harvest and efficacious based on 100 percent muscle viability after harvest and zero conversions to open technique. There appears to be little to no long-term functional deficit or pain from muscle harvest. Given these results and their own prestudy guidelines, the robotic latissimus dorsi qualifies for 510(k) submission by Intuitive Surgical and approval by the U.S. FDA. Therapeutic, IV.

Cervical Total Disk Replacement: Available Implant Size Matters.

This study was a post hoc analysis of data collected from 2 Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trials. The purposes of this study were to: (1) measure disk space heights adjacent to the level to be treated with a total disk replacement (TDR); (2) analyze cervical disk space heights to be replaced with TDR; and (3) investigate the frequency of use of a smaller height TDR when available. Cervical TDR produces outcomes noninferior or superior to anterior cervical discectomy and fusion. While the restoration of the height of a collapsed, degenerated disk is a surgical goal, there are potential problems with overdistracting the segment with an implant. Disk heights were measured using radiographs from the 1-level Simplify Cervical Artificial Disk IDE trial, producing values for 259 levels adjacent to the treated level and 162 treated levels. The device is available in 4, 5, and 6 mm heights. The 4 mm height became available only after treatment was 13% complete in the single-level trial and was available for all of the 2-level trial. Measurements of 259 adjacent levels found that 55.2% of disk spaces had a height of <4 mm. Among operated levels, 82.7% were <4 mm. When a 4 mm TDR was available, it was used in 38.4% of operated levels in the 1-level trial and 54.3% of levels in the 2-level trial. Among nonoperated levels, 55.2% were of height <4 mm, suggesting that TDRs of greater heights may potentially overdistract the disk space. The 4 mm TDR was selected by surgeons in 49.4% of all implanted levels, suggesting a preference for smaller TDR height. Further investigation is warranted to determine if the lower height implants are related to clinical and/or radiographic outcomes. Level III.

A randomized comparison of loss of resistance versus loss of resistance plus electrical stimulation: effect on success of thoracic epidural placement

BackgroundLoss of resistance (LOR) for epidural catheter placement has been utilized for almost a century. LOR is a subjective endpoint associated with a high failure rate. Nerve stimulation (NS) has been described as an objective method for confirming placement of an epidural catheter. We hypothesized that the addition of NS to LOR would improve the success of epidural catheter placement.MethodsOne-hundred patients were randomized to thoracic epidural analgesia (TEA) utilizing LOR-alone or loss of resistance plus nerve stimulation (LOR + NS). The primary endpoint was rate of success, defined as loss of sensation following test dose. Secondary endpoints included performance time. An intention-to-treat analysis was planned, but a per-protocol analysis was performed to investigate the success rate when stimulation was achieved.ResultsIn the intention-to-treat analysis there was no difference in success rates (90% vs 82% [LOR + NS vs LOR-alone]; P = 0.39). The procedural time increased in the LOR + NS group (33.9 ± 12.8 vs 24.0 ± 8.0 min; P < 0.001). The per-protocol analysis found a statistically higher success rate for the LOR + NS group compared to the LOR-alone group (98% vs. 82%; P = 0.017) when only patients in whom stimulation was achieved were included.ConclusionsAddition of NS technique did not statistically improve the success rate for epidural placement when analyzed in an intention-to-treat format and was associated with a longer procedural time. In a per-protocol analysis a statistically higher success rate for patients in whom stimulation was obtained highlights the potential benefit of adding NS to LOR.Trial registrationClinicalTrials.gov identifier NCT03087604 on 3/22/2017; Institutional Review Board Wake Forest School of Medicine IRB00039522, Food and Drug Administration Investigational Device Exemption: G160273.

Five-year Outcomes of the COMMENCE Trial Investigating Aortic Valve Replacement With RESILIA Tissue

BackgroundThe COMMENCE trial was conducted to evaluate the safety and effectiveness of aortic valve replacement using a bioprosthesis with novel RESILIA tissue (Edwards Lifesciences). RESILIA tissue is incorporated in the INSPIRIS RESILIA aortic valve (Edwards Lifesciences). MethodsPatients underwent clinically indicated surgical aortic valve replacement with a bovine pericardial bioprosthesis (model 11000A; Edwards Lifesciences) in a prospective, multinational, multicenter (n = 27), US Food and Drug Administration Investigational Device Exemption trial. Events were adjudicated by an independent clinical events committee, and echocardiograms were analyzed by an independent core laboratory. Outcomes through an observational period of 5 years are reported. ResultsBetween January 2013 and March 2016, 689 patients received the study valve. Mean patient age was 66.9 ± 11.6 years; Society of Thoracic Surgeons Predicted Risk of Mortality was 2.0% ± 1.8%; and 23.8%, 49.9%, and 24.4% of patients were New York Heart Association functional class I, II, and III at baseline, respectively. Through December 11, 2020 the follow-up duration was 4.3 ± 1.4 years, and the completeness of follow-up over the observational period was 95.5%. Early (<30 days) all-cause mortality was 1.2%, stroke 1.6%, and major paravalvular leak 0.1%. Five-year actuarial freedom from all-cause mortality, structural valve deterioration, and all-cause reintervention were 89.2%, 100%, and 98.7%, respectively. At 5 years the effective orifice area was 1.6 ± 0.5 cm2, mean gradient was 11.5 ± 6.0 mm Hg, 97.8% of patients were class I/II, and 97.8% and 96.3% of patients had none/trace paravalvular and transvalvular regurgitation, respectively. ConclusionsThe safety and hemodynamic performance of this aortic bioprosthesis with RESILIA tissue through 5 years are encouraging, with clinically stable hemodynamics, minimal regurgitation, and no evidence of structural valve deterioration.

Incidence and Resolution Strategies for Early-Onset Postoperative Leg Pain Following Lumbar Total Disc Replacement.

Lumbar total disc replacement (TDR) has produced results similar or superior to fusion in treating symptomatic disc degeneration. Some patients have reported onset of leg pain early after surgery. Little information is available specifically on this problem. The purpose of this study was to investigate the incidence of early-onset postoperative leg pain following lumbar TDR and to describe strategies for its treatment. The study was based on a post hoc analysis of prospectively collected adverse event data from 283 patients in the activL Food and Drug Administration investigational device exemption study. Early-onset leg pain was defined as occurring between 0 and 4 weeks postprocedure, and the baseline visual analog scale score in the affected leg(s) was <25 (of 100). The treatment types these patients received were analyzed. Among 283 patients, 26 (9.2%) had an early-onset leg pain event. The majority of these events resolved (20/26, 76.9%). Of those resolving, 55% (11/20) did so within 3 months. Most patients received at least 1 drug treatment for leg pain (92.3%). Of those receiving drug therapy, the most common type was neurogenic (61.5%), followed by narcotics (46.2%). Steroid use was prescribed in 30.8%. The majority of resolved cases were not on narcotics and resolved with neurogenic drugs. Three patients went on to have surgery, none of whom benefited from it. Age, body mass index, and baseline disability scores were predictive of time to resolution. Early-onset postoperative leg pain occurred in approximately 10% of lumbar TDR patients. The majority of events resolved, often within 3 months. Treatment with conservative care, including medication(s), was more effective in resolving symptoms rather than surgery. This study provides useful information for providers and patients on the incidence, treatment, and resolution of leg pain with onset after lumbar TDR and not related to direct neural compression identified by imaging. 2.

4. Single-level cervical disc replacement using a PEEK-on-ceramic implant: Results of a multicenter FDA IDE trial with 24-month follow up

<h3>BACKGROUND CONTEXT</h3> Many early cervical total disc replacements (TDRs) produced motion through a ball-and-socket action, with metal endplates articulating with a plastic core. PEEK is used increasingly for spinal implants due to its mechanical properties and lack of artifact on imaging. A cervical TDR was designed with commercially pure titanium-coated PEEK endplates and a biconvex zirconia toughened alumina ceramic core. <h3>PURPOSE</h3> The purpose of this study was to compare this PEEK-on-ceramic TDR to anterior cervical discectomy and fusion (ACDF) to treat single-level cervical disc degeneration. <h3>STUDY DESIGN/SETTING</h3> This was a prospective, nonrandomized, multicenter Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial comparing the investigational group to a propensity-matched historic control group. <h3>PATIENT SAMPLE</h3> Patients received the PEEK-on-ceramic Simplify® Cervical Artificial Disc (n=150 patients from 16 sites). The historic control group included 117 propensity-matched ACDF patients from an earlier cervical TDR IDE trial employing the same inclusion/exclusion criteria. All patients were treated for single-level symptomatic cervical disc degeneration. <h3>OUTCOME MEASURES</h3> The primary outcome was a composite 5-point success classification at 24-month follow-up requiring: >15 point (of 100) improvement in Neck Disability Index (NDI) score; 2) maintenance/improvement in neurologic status; 3) no device failure; 4) no reoperation/revision/removal and/or supplemental fixation at the index level, and 5) no major adverse events. Outcome measures included NDI, visual analog scale (VAS) assessing neck and arm pain, neurological status, adverse events and subsequent surgery. Radiographic assessment included flexion/extension range of motion. Facet joints were assessed at 24 months comparing pre- to postoperative MRI images using a published 4-point scale. <h3>METHODS</h3> Evaluations were performed preoperatively and postoperatively within 2 and 6 weeks, and 3, 6, 12 and 24 months. The control was propensity match with ACDF patients from an earlier TDR vs ACDF trial, which used the same inclusion criteria and primary outcome assessments. <h3>RESULTS</h3> The overall composite success rate was significantly greater in the TDR group vs ACDF (93.0% vs 73.6%; p<0.001). Mean NDI, neck pain and arm pain scores improved significantly in both groups at all follow-up points. Mean NDI scores in the TDR group were significantly lower than ACDF scores at all follow-up points all p<0.01). Secondary surgical intervention was undertaken in 4 (2.7%) patients at the index level in the TDR group and 6 (5.1%) in the ACDF group. There were no significant differences in the rates of serious adverse events when comparing the two groups. The mean segmental range of motion of the treated level in the TDR group was 7.3° prior to surgery. This increased to 8.6° at 3-month follow-up and continued to increase to 9.6° at 24 months (p<0.001). Facet joint assessment by MRI at 24-month follow-up in the TDR group showed little change from preoperative. <h3>CONCLUSIONS</h3> The results of this study found that the Simplify® Cervical Artificial Disc produced outcomes similar or superior on some measures, including superiority in the composite success classification, compared with ACDF, for the treatment of single-level symptomatic cervical disc degeneration. ROM at the treated level increased from the preoperative value and was maintained throughout follow-up. Safety of the PEEK-on-ceramic disc was established with no device failures in the series. These results support that the device is a viable alternative to ACDF. <h3>FDA DEVICE/DRUG STATUS</h3> Simplify Cervical Disc Replacement (Approved for this indication)