Summary of the FDA virtual public workshop on spinal device clinical review held on September 17, 2021.

The mission of Food and Drug Administration (FDA)'s Center for Devices and Radiological Health is to protect and promote public health. It assures that patients and providers have timely and continued access to safe, effective, and high-quality medical devices and safe radiation-emitting products by providing meaningful and timely information about the products we regulate and the decisions we make. On September 17, 2021, an FDA workshop was held to provide information to stakeholders, including members of the spine community, device manufacturers, regulatory affairs professionals, clinicians, patients, and the general public regarding FDA regulations, guidance and regulatory pathways related to spinal device clinical review. It was not intended to communicate any new policies, processes, or interpretations regarding medical device marketing authorizations. This workshop consisted of individual presentations, group discussions, question and answer sessions, and audience surveys. Information-sharing included discussions related to patient-reported outcomes, clinician-reported outcomes, observer-reported outcomes, and performance outcomes. Discussions involving external subject matter experts covered topics related to spinal device clinical studies including definition of a target population, enrollment criteria, strategies for inclusion of under-represented patient groups, reporting of adverse event and secondary surgical procedures, clinical study endpoints, and clinical outcome assessments. A meeting transcript and webcast workshop link are currently posted on the FDA website. Important related issues and challenges were discussed, and an exciting range of new ideas and concepts were shared which hold promise to advance regulatory science, patient care and future innovation related to spinal devices.

Determination of Work Relative Value Units for Management of Lumbar Spinal Stenosis by Open Decompression and Interlaminar Stabilization.

BACKGROUND: Effective January 1, 2017, open surgical decompression and interlaminar stabilization (ILS) received a Category I Current Procedural Terminology (CPT®) code 22867. The current work relative value units (wRVUs) assigned to the procedure of 13.5 are not reflective of the amount of work involved. During the survey process, CPT® 22867 was erroneously assessed with a percutaneous "sister" code (CPT® 22869), which is performed with no decompression (but within the same new "family") and primarily by nonsurgeons. However, similar CPT® code descriptors assigned to each of these new codes undermined their procedural differences during the survey process and generated confusion among physician survey responders, the American Medical Association/Specialty Society Relative Value Scale Update Committee (RUC), and ultimately the Centers for Medicare and Medicaid Services (CMS) regarding the value of ILS. The resulting physician payment determination for the ILS procedure has had severe deleterious effects on this procedure being offered to lumbar spinal stenosis (LSS) patients. Our independent society-driven survey presents new data that assess the accuracy of the assigned wRVUs for CPT® 22867. METHODS: An independent survey was driven by the International Society for the Advancement of Spine Surgery (ISASS) in November 2018 and sent to 58 US surgeons with experience performing open decompression with ILS (CPT® 22867) and without financial conflicts of interest as analogous to RUC survey financial disclosure requests. Respondents were asked to compare CPT® 22867 with a list of 10 other comparator CPT® codes reflective of common spine surgeries. The survey presented each comparator CPT® code with its code descriptor and corresponding wRVUs alongside the code descriptor for CPT® 22867. A patient vignette was also provided that describes a typical clinical scenario for the surveyed procedure. Respondents were then asked to indicate which comparator CPT® code on the reference list is most similar to the survey code descriptor and typical patient/service vignette provided, as well as specify estimated wRVUs for CPT® 22867 relative to their selected comparator CPT® code. The surgeons' responses were analyzed to determine comparator CPT® codes and estimated wRVUs. RESULTS: Among the 28 surgeons who responded to the survey, both open decompression codes (57.1%) and fusion codes (42.9%) were chosen as most similar to the typical patient/service for CPT® 22867. Furthermore, the laminectomy procedure (CPT® 63047) was chosen as the surveyed surgeons' model response for a reference procedure in terms of similar work intensity and time for CPT® 22867. After calculating the difference between the selected comparator codes and estimated wRVUs, nearly all respondents had a positive calculated difference, indicating that surgeons selected wRVUs lower than they deemed appropriate as a result of the listed CPT® codes they were required to use. In the spirit of the Rasch analysis, the regression analysis estimated wRVUs for CPT® 22867 that are greater than its assigned wRVUs (13.5) and its most comparable procedure (CPT® 63047; reference wRVUs: 15.37). DISCUSSION AND CONCLUSIONS: The survey results indicate that the wRVUs assigned to CPT® 22867 are significantly undervalued at 13.50 and have directly resulted in the underreimbursement for surgeons performing the ILS procedure. This misvaluation of the code has created a supply-and-demand anomaly in which the rate of ILS procedures has flatlined despite increasing rates of fusion procedures and an increasing older population. This anomaly is a cause of concern for policy makers and the health care community for the future of safeguarding patient welfare and procedural innovation. Therefore, understanding the clinical economic impact and appropriately addressing potential misvalued codes, such as the ILS procedure, are critical to protecting the future of patient care.

Guideline summary review: an evidence-based clinical guideline for the diagnosis and treatment of low back pain.

BACKGROUND CONTEXT: The North American Spine Society's (NASS) Evidence Based Clinical Guideline for the Diagnosis and Treatment of Low Back Pain features evidence-based recommendations for diagnosing and treating adult patients with nonspecific low back pain. The guideline is intended to reflect contemporary treatment concepts for nonspecific low back pain as reflected in the highest quality clinical literature available on this subject as of February 2016. PURPOSE: The purpose of the guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for adult patients with nonspecific low back pain. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. STUDY DESIGN: This is a guideline summary review. METHODS: This guideline is the product of the Low Back Pain Work Group of NASS' Evidence-Based Clinical Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members utilized NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guideline was submitted to an internal and external peer review process and ultimately approved by the NASS Board of Directors. RESULTS: Eighty-two clinical questions were addressed, and the answers are summarized in this article. The respective recommendations were graded according to the levels of evidence of the supporting literature. CONCLUSIONS: The evidence-based clinical guideline has been created using techniques of evidence-based medicine and best available evidence to aid practitioners in the diagnosis and treatment of adult patients with nonspecific low back pain. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flowchart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx.

Superiority Claims for Spinal Devices: A Systematic Review of Randomized Controlled Trials.

STUDY DESIGN: Systematic review. OBJECTIVES: Superiority claims for medical devices are commonly derived from noninferiority trials, but interpretation of such claims can be challenging. This study aimed to (a) establish the prevalence of noninferiority and superiority designs among spinal device trials, (b) assess the frequency of post hoc superiority claims from noninferiority studies, and (c) critically evaluate the risk of bias in claims that could translate to misleading conclusions. METHODS: Study bias was assessed using the Cochrane Risk of Bias Tool. The risk of bias for the superiority claim was established based on post hoc hypothesis specification, analysis of the intention-to-treat population, post hoc modification of a priori primary outcomes, and sensitivity analyses. RESULTS: Forty-one studies were identified from 1895 records. Nineteen (46%) were noninferiority trials. Fifteen more (37%) were noninferiority trials with a secondary superiority hypothesis specified a priori. Seven (17%) were superiority trials. Of the 34 noninferiority trials, 14 (41%) made superiority claims. A medium or high risk of bias was related to the superiority claim in 9 of those trials (64%), which was due to the analyzed population, lacking sensitivity analyses, claims not being robust during sensitivity analyses, post hoc hypotheses, or modified endpoints. Only 4 of the 14 (29%) noninferiority studies provided low bias in the superiority claim, compared with 3 of the 5 (60%) superiority trials. CONCLUSIONS: Health care decision makers should carefully evaluate the risk of bias in each superiority claim and weigh their conclusions appropriately.

Does the presence of the fibronectin-aggrecan complex predict outcomes from lumbar discectomy for disc herniation?

BACKGROUND CONTEXT: Protein biomarkers associated with lumbar disc disease have been studied as diagnostic indicators and therapeutic targets. Recently, a cartilage degradation product, the fibronectin-aggrecan complex (FAC) identified in the epidural space, has been shown to predict response to lumbar epidural steroid injection in patients with radiculopathy from herniated nucleus pulposus (HNP). PURPOSE: Determine the ability of FAC to predict response to microdiscectomy for patients with radiculopathy due to lumbar disc herniation STUDY DESIGN/SETTING: Single-center prospective consecutive cohort study. PATIENT SAMPLE: Patients with radiculopathy from HNP with concordant symptoms to MRI who underwent microdiscectomy. OUTCOMES MEASURES: Oswestry disability index (ODI) and visual analog scores (VAS) were noted at baseline and at 3-month follow-up. Primary outcome of clinical improvement was defined as patients with both a decrease in VAS of at least 3 points and ODI >20 points. METHODS: Intraoperative sampling was done via lavage of the excised fragment by ELISA for presence of FAC. Funding for the ELISA was provided by Cytonics, Inc. RESULTS: Seventy-five patients had full complement of data and were included in this analysis. At 3-month follow-up, 57 (76%) patents were "better." There was a statistically significant association of the presence of FAC and clinical improvement (p=.017) with an 85% positive predictive value. Receiver-operating-characteristic (ROC) curve plotting association of FAC and clinical improvement demonstrates an area under the curve (AUC) of 0.66±0.08 (p=.037). Subset analysis of those with weakness on physical examination (n=48) plotting the association of FAC and improvement shows AUC on ROC of 0.81±0.067 (p=.002). CONCLUSIONS: Patients who are "FAC+" are more likely to demonstrate clinical improvement following microdiscectomy. The data suggest that the inflammatory milieu plays a significant role regarding improvement in patients undergoing discectomy for radiculopathy in lumbar HNP, even in those with preoperative weakness. The FAC represents a potential target for treatment in HNP.

Introduction to Additive Manufacturing and Three-Dimensional Printing in Orthopaedics.

Additive manufacturing involves the construction of devices via the layer-by-layer deposition of materials. Additive manufacturing, which also is referred to as three-dimensional printing, is different from traditional machining, which involves the subtraction of material from a workpiece. Although traditional machining methods have been used in the field of manufacturing for decades, a recent rise in the commercial use of additive manufacturing has occurred in the field of orthopaedic surgery. Orthopaedic surgeons should understand the pertinent history of three-dimensional printing with regard to the field of manufacturing technology and the manner in which recent advances in additive manufacturing have allowed for new product designs with musculoskeletal applications. In addition, it is helpful to be aware of the regulatory aspects of additive manufacturing to ensure the safe and effective use of orthopaedic surgical devices created via three-dimensional printing.

Applications of Three-Dimensional Printing in Orthopaedic Surgery.

Orthopaedic surgeons should be aware of the variety of applications of three-dimensional printing, which range from rough-and-ready applications, such as rapid prototyping of implant designs with the use of polymers to the fabrication of patient-specific implants and custom implants with the use of the principles of metallurgy. The local manufacture of low-cost prosthetic devices in third-world nations is the best example of the potential application of three-dimensional printing. Orthopaedic surgeons should understand the multiple applications of three-dimensional printing, including prototyping of anatomy, implants, orthotics, patient-specific instrumentation, and implants that incorporate porous structures and accommodate complex anatomy, as well as the future of biologically active three-dimensional printing. It is helpful to be aware of the types of three-dimensional printing that are currently used in the clinical setting, those that are commercially available, and those under development.

Three-Dimensional Printing and Tissue Engineering in Orthopaedics.

Additive manufacturing and three-dimensional printing technology may revolutionize tissue-engineering strategies. Many clinical needs, including multitissue regeneration, remain unmet among patients with orthopaedic conditions. Ongoing research efforts in three-dimensional printing, including cell-containing bioinks for bioprinting, have resulted in acellular and cellular biomaterials that may help regenerate or replace damaged or missing biologic tissues. Recent advances in additive manufacturing aid in the preservation of biologic activity, such as the retention of growth factors, which may affect the delivery of safe, cost-effective, and efficacious bone graft substitutes for orthopaedic patients.

Pivotal trials of orthopedic surgical devices in the United States: predominance of two-arm non-inferiority designs.

BACKGROUND: The United States Food and Drug Administration (FDA) reviews class III orthopedic devices submitted for premarket approval with pivotal clinical trials. The purpose of this study was to determine the types of orthopedic devices reviewed, the design of their pivotal clinical trials, and the subjective factors affecting the interpretation of clinical trial data. METHODS: Meetings of the FDA Orthopaedic and Rehabilitation Devices Panel were identified from 2000-2016. Meeting materials were collected from FDA electronic archives and notes were made regarding the device-type and subsequent approval and recall, the design of pivotal clinical trials, and issues of trial interpretation debated during panel deliberations. RESULTS: The panel was convened on 29 separate occasions over the course of 35 days to deliberate 38 distinct topics. Of these, 23 topics included clinical data submitted for approval of a device, and two topics were excluded. Of the 23 devices, five were biologic, three were hip arthroplasty, three were disc arthroplasty, two were viscosupplementation, three were interspinous process devices, and seven were other devices. Of the 23 pivotal trials, 20 (87.0%) were randomized controlled trials (RCTs), consisting of 13 (65.0%) non-inferiority trials and 7 (35.0%) superiority trials, and all RCTs were two-arm trials. At panel, the most commonly debated issues were related to the design and interpretation of non-inferiority trials. CONCLUSIONS: A broad array of device types is reviewed by the FDA. The predominance of two-arm non-inferiority trials as pivotal studies indicates that the nuances of their design and interpretation are commercially important.

Spinal devices in the United States-investigational device exemption trials and premarket approval of class III devices.

BACKGROUND CONTEXT: Recently, there has been increased public awareness of regulatory actions by the United States Food and Drug Administration (FDA) on spinal devices. There has also been increased scrutiny of the pivotal clinical trials of these devices. PURPOSE: To investigate the premarket approval (PMA) of class III spinal devices in the United States since the turn of the century. To explore clinically relevant issues that affect the interpretation of investigational device exemption trials. STUDY DESIGN: Literature review. METHODS: From 2000 to 2015, data on PMA applications for spinal devices were obtained from two sources. First, meetings of FDA's Orthopaedic and Rehabilitation Devices Panel were identified from the Federal Register. Second, the FDA database of approved PMA applications was queried. For each device, two authors reviewed all archival data. There was no external source of funding. RESULTS: Twenty-one devices met the study criteria. There were 76.2% that received approval and 47.6% that went to panel. Arthroplasty devices were most common (52.4%), least likely to go to panel (3 of 11), and most likely to be approved after panel (3 of 3). Biologic devices were most likely to go to panel (3 of 3) and least likely to be approved after panel (1 of 3). Before and after 2009, there was no decrease in the number of spinal devices approved. All 21 devices were studied in a pivotal clinical trial. All trials except one were randomized controlled trials, and all trials except one were two-arm noninferiority designs. CONCLUSIONS: There has been no decrease in the number of new FDA-approved class III spinal devices since the turn of the century. The majority of devices have been for cervical arthroplasty. By contrast, biologic devices were most likely to go to panel and least likely to be approved after panel. The pivotal trials for nearly all devices were randomized, two-arm, noninferiority trials.

Does a fibronectin and aggrecan complex play a role in painful vertebral disks?

OBJECTIVE: To determine the presence of a fibronectin-aggrecan complex (FAC) in the disk space of persons with chronic low back pain as relates to provocative diskography. DESIGN: A single-center prospective consecutive case series. SETTING: A single private practice setting. PATIENTS: Thirty-seven patients with symptomatic degenerative disk disease of the cervical, thoracic, or lumbar spine undergoing provocative diskography to identify a source of pain. METHODS: Diskographic lavage for analysis was simultaneously performed at each disk level injected during diskography. MAIN OUTCOME MEASURES: Visual analog scale (VAS) pain scores, Pfirrmann magnetic resonance imaging grade, and biochemical analysis of disk material were statistically analyzed. RESULTS: A total of 105 levels in 37 patients had a complete set of data (mean age 43.2 ± 11.9 years; 15 male/22 female). The FAC was present in 43 of 108 levels and in at least one level in 25 of 37 patients. The Pfirrmann magnetic resonance imaging grade did not differ between complex-positive and negative levels (P = .125), nor did the intraoperative VAS (IO-VAS) score for pain by level (P = .206). A significant but loose correlation was found between Pfirrmann grade and IO-VAS (R(2) = 0.4, P < .001), but no significant correlation was found between VAS or IO-VAS and complex concentration (R(2) = 0.08, P = .11 and R(2) = 0.003, P = .5). CONCLUSIONS: The FAC was identified in some painful disks by diskography. There was no significant correlation between the Pfirrmann grade or pre/intraoperative pain scores during diskography and complex concentrations within the disk measured by disk lavage.

Platelet-rich plasma increases matrix metalloproteinases in cultures of human synovial fibroblasts.

BACKGROUND: The effect of platelet-rich plasma on chondrocytes has been studied in cell and tissue culture. Less attention has been given to the effect of platelet-rich plasma on nonchondrocytic cell lineages within synovial joints, such as fibroblast-like synoviocytes, which produce cytokines and matrix metalloproteinases (MMPs) that mediate cartilage catabolism. The purpose of the present study was to determine the effect of platelet-rich plasma on cytokines and proteases produced by fibroblast-like synoviocytes. METHODS: Platelet-rich plasma and platelet-poor plasma from harvested autologous blood were prepared with a commercially available system. Fibroblast-like synoviocytes were treated with platelet-rich plasma, platelet-poor plasma, recombinant PDGFßß (platelet-derived growth factor ßß), or phosphate-buffered saline solution and incubated at 37°C for forty-eight hours. The concentrations of IL-1ß (interleukin-1ß), IL-1RA (IL-1 receptor antagonist), IL-6, IFN-γ (interferon-γ), IP-10 (interferon gamma-induced protein 10), MCP-1 (monocyte chemotactic protein-1), MIP-1ß (macrophage inflammatory protein-1ß), PDGFßß, RANTES, TNF-α (tumor necrosis factor-α), VEGF (vascular endothelial growth factor), MMP-1, MMP-3, and MMP-9 in the culture medium were determined by multiplex immunoassay. RESULTS: Platelet-rich plasma cultured in medium contained multiple catabolic mediators in substantial concentrations, including MMP-9 (15.8 ± 2.3 ng/mL) and MMP-1 (2.5 ± 0.8 ng/mL), as well as proinflammatory mediators IL-1ß, IL-6, IFN-γ, IP-10, MCP-1, MIP-1ß, RANTES, and TNF-α in concentrations between 20 pg/mL and 20 ng/mL. Platelet-poor plasma contained significantly lower concentrations of these compounds. Platelet-rich plasma was used to treat human fibroblast-like synoviocytes, and the resulting concentrations of mediators were corrected for the concentrations in the platelet-rich plasma alone. Compared with untreated fibroblast-like synoviocytes, synoviocytes treated with platelet-rich plasma exhibited significantly greater levels of MMP-1 (363 ± 94.0 ng/mL, p = 0.018) and MMP-3 (278 ± 90.0 ng/mL, p = 0.018). In contrast, platelet-poor plasma had little effect on mediators secreted by the synoviocytes. PDGFßß-treated fibroblast-like synoviocytes exhibited a broad proinflammatory cytokine response at four and forty-eight hours. CONCLUSIONS: Platelet-rich plasma was shown to contain a mixture of anabolic and catabolic mediators. Synoviocytes treated with platelet-rich plasma responded with substantial MMP secretion, which may increase cartilage catabolism. Synoviocytes responded to PDGF with a substantial proinflammatory response.

Correlation of intra-articular ankle pathology with cytokine biomarkers and matrix degradation products.

BACKGROUND: Articular cartilage degeneration is mediated by inflammatory cytokines and fragments of structural matrix proteins. Few studies have examined the role of these biomarkers in intra-articular pathology of the ankle. METHODS: Four groups of patients with increasing ankle pathology were enrolled. Group 1 included controls with no pain who underwent unrelated forefoot surgery. Group 2 included patients undergoing arthroscopy with intraoperative mild chondrosis. Group 3 included patients undergoing arthroscopy with moderate/severe chondrosis, osteochondral lesions, impingement, or loose bodies. Group 4 included positive controls with severe arthrosis undergoing ankle arthrodesis/arthroplasty. Ankle fluid was obtained by intra-articular aspiration and was assayed for IL-6, IFN-γ, MCP, MIP-1ß, and fibronectin-aggrecan complex (FAC), a matrix-degradation marker. There were 36 patients total, 21 males and 15 females with a mean age 45 (±16; range 18 to 76) years and a mean VAS for pain of 4.7 (±3.5; range 0 to 9). In groups 1 through 4, there were 11, 6, 15 and 4 patients respectively. RESULTS: The mean values of MCP-1 were 49.8 (±8.0) for minimal pathology and 133.9 (±33.0) for substantial pathology (pg/ml). The mean values of the FAC were 2.83 (±1.16) for minimal pathology and 9.62 (±2.23) for substantial pathology (optical density at 450 nm). The groups differed significantly in age, preoperative VAS, FAC, IL-6, and MCP-1 (p<0.05). CONCLUSION: There are differences in FAC and MCP-1 with increasing grades of severity of intra-articular pathology. CLINICAL RELEVANCE: These tests may play a role in determining the necessity for arthroscopy or intra-articular procedures in equivocal candidates.

Failure strength of lumbar spinous processes loaded in a tension band model.

OBJECT: There has been increasing interest in spinous process tension band devices, as distinct from spinous process spacers and plates. The purpose of this study was to load spinous processes caudally at L-4 and cranially at L-5 parallel to the long axis of the spine in a biomechanical model of tension band loading. The goal was to provide normative data for the design of a spinous process tension band device after varying degrees of surgical decompression and across varying bone mineral densities (BMDs). METHODS: Fresh-frozen L4-5 lumbar vertebrae pairs were divided into 3 surgical groups: intact, midline-sparing decompression (laminotomy and medial facetectomy), and midline decompression with foraminotomy (one-half of spinous process resected, laminotomy, and medial facetectomy). After decompression, specimens were disarticulated into isolated L-4 and L-5 vertebrae. Each vertebra was loaded to failure in a caudal (L-4) or cranial (L-5) direction parallel to the long axis of the spine via a 6-mm-wide strap looped around the spinous process. Failure strength and mode were recorded. RESULTS: Seventeen L-4 and L-5 lumbar vertebrae were tested from 17 cadavers. There were 10 male (59%) and 7 female (41%) cadavers, with a mean age of 66.6 ± 16.5 years (range 41-100 years) and a mean BMD of 1 ± 0.23 g/cm(2) (range 0.66-1.34 g/cm(2)); the mean is expressed ± SD throughout. For data analysis, specimens were grouped into those with no or midline-sparing decompression (Group 1: 11 of 17) and those with midline decompression (Group 2: 6 of 17). At L-4, the mean failure strength for Group 1 was 453 ± 162 N, and for Group 2 it was 264 ± 99 N (p = 0.02; Cohen's d = 1.4). At L-5, the mean failure strength for Group 1 was 517 ± 190 N, and for Group 2 it was 269 ± 184 N (p = 0.02; Cohen's d = 1.3). There was no significant difference in failure strength between the intact and midline-sparing decompression groups at L-4 (p = 0.91) or L-5 (p = 0.41). CONCLUSIONS: Across specimens with a wide range of BMDs, midline-sparing decompression was not found to decrease the mean failure strength of the L-4 and L-5 spinous processes (453 and 517 N, respectively), whereas midline surgical decompression decreased the failure strength of these processes (264 and 269 N, respectively) in a biomechanical model of tension band loading relevant to the design of a tension band device.

Effects of arm position on maximizing intra-articular visualization of the biceps tendon: a cadaveric study.

PURPOSE: The purpose of this study was to assess the intra-articular length of the biceps tendon in various shoulder and arm positions and identify the position in which the extra-articular portion of the tendon is maximally visualized within the glenohumeral joint. METHODS: We measured 18 positions in 4 fresh-frozen cadaveric shoulders for a total of 72 measurements. In each measurement the position of the proximal biceps tendon was measured relative to a baseline measurement in neutral position (0° shoulder flexion, 0° shoulder abduction, 0° elbow flexion, 0° shoulder rotation). Positions measured ranged between the following: 0° and 30° shoulder flexion; 0° and 40° shoulder abduction; 0° and 90° elbow flexion; and 0° neutral, 30° internal, and 30° external shoulder rotation. RESULTS: The position creating the greatest increase in intra-articular biceps tendon length from baseline was 30° shoulder flexion, 40° shoulder abduction, 90° elbow flexion, and 0° rotation. On average, 56% of the tendon within the bicipital groove is brought into view by the maximal position relative to baseline. In maximizing intra-articular biceps tendon length, the effect of elbow flexion was highly significant (P < .001) and the combined effect of shoulder flexion-abduction was significant (P = .016). CONCLUSIONS: The position of 30° shoulder flexion, 40° shoulder abduction, and 90° elbow flexion significantly increases the excursion of the proximal biceps tendon relative to a neutral position. Over 50% of the tendon within the bicipital groove at baseline can be pulled out of the groove by placing the extremity in the maximal position and using an arthroscopic probe. Rotation of the humerus does not improve intra-articular excursion. CLINICAL RELEVANCE: Maximizing the intra-articular tendon length by arm positional change is likely to be useful for arthroscopic examination of the biceps tendon.

The in vitro chondrotoxicity of single-dose local anesthetics.

BACKGROUND: The administration of amide-type local anesthetics to cartilaginous tissues has revealed potential chondrotoxicity. PURPOSE: This study evaluated whether administration of single doses of 1% lidocaine, 0.25% bupivacaine, and 0.5% ropivacaine resulted in decreased chondrocyte viability or cartilage matrix degradation in vitro. STUDY DESIGN: Controlled laboratory study. METHODS: Monolayer human chondrocytes and intact cartilage samples were cultured for 1 week in media. Each drug was delivered in a custom bioreactor over its clinical duration of action. A Live/Dead Viability/Cytotoxicity Assay was used to determine the ratio of dead to live cells for monolayer chondrocyte cultures compared with controls. Damage to the cartilage extracellular matrix (ECM) in en bloc cartilage samples was evaluated by analysis of DNA, glycosaminoglycan (GAG), and collagen content. RESULTS: Chondrocytes treated for 3 hours with a single dose of 1% lidocaine exhibited significantly more cell death (7.9%) compared with control media (2.9%; P < .001). No significant difference in cell death was observed in chondrocytes treated for 6 hours with 0.25% bupivacaine (2.7%) versus controls (2.8%; P = .856) or cells treated for 12 hours in 0.5% ropivacaine (2.9%) versus controls (2.4%; P = .084). There was no significant difference in GAG expression (P = .627) or DNA-normalized GAG expression (P = .065) between the intact cartilage treatment groups; however, the DNA-normalized GAG expression was markedly lower in cartilage cultures treated with 1% lidocaine (3.36 ± 1.15) compared with those in control media (7.61 ± 3.83). CONCLUSION: The results of this in vitro study indicate that a single-dose administration of 1% lidocaine resulted in a significant decrease in chondrocyte viability when compared with control cultures. CLINICAL RELEVANCE: Single-dose injections of 1% lidocaine may be significantly chondrotoxic, and further investigation regarding in vivo chondrotoxicity appears warranted.

Bearing surfaces for total disc arthroplasty: metal-on-metal versus metal-on-polyethylene and other biomaterials.

BACKGROUND CONTEXT: Concerns about the effect of metallic wear debris from metal-on-metal bearing surfaces in total hip arthroplasty have increased. Some spinal arthroplasty devices include metal-on-metal bearing surfaces. PURPOSE: To review the literature for clinical reports of complications because of wear debris from metal-on-metal spinal arthroplasty devices. To review the biology of wear debris from metal-on-metal bearing surfaces drawn from the hip arthroplasty literature and place it in the context of global regulatory actions and clinical and laboratory studies. STUDY DESIGN: Literature review. METHODS: To identify clinical reports, the PubMed database from the United States National Library of Medicine was queried using Medical Subject Headings terms and additional keyword terms. In addition, experts from academia and regulatory agencies were questioned regarding their knowledge of reports, including experts who attended the US Food and Drug Administration roundtable in September 2010. RESULTS: Three case reports and one case series including seven total cases were identified in which abnormal inflammatory reactions and soft-tissue masses after metal-on-metal disc replacements were consistent with pseudotumor and metal hypersensitivity. Spinal cases are present as pain and neurologic symptoms. On plain radiography, there is no clear periprosthetic osteolysis or loosening. On magnetic resonance imaging, there is increased magnetic susceptibility artifact because of metallic debris that renders images inadequate. Computed tomography myelography demonstrates a soft-tissue mass, which exhibits epidural extension surgically. Histologically, large areas of necrotic debris and exudates are interspersed with chronic inflammatory cells. Lymphocyte or macrophage predominance is determined by the rate of wear and the presence of gross, microscopic, or submicron metallic wear debris. The metallurgy of the involved devices is cobalt-chromium-molybdenum (CoCrMo) alloy, and the bearing surface is CoCrMo-on-CoCrMo. CONCLUSIONS: Metal-on-metal spinal arthroplasty devices are subject to postoperative complications because of metallic wear debris with similar clinical, radiographic, histologic, gross anatomic, and device-related features to those found in metal-on-metal bearing surfaces in total hip arthroplasty.

Is the fibronectin-aggrecan complex present in cervical disk disease?

OBJECTIVE: To investigate the presence of inflammatory cytokines and the fibronectin-aggrecan complex (FAC) in persons undergoing surgical treatment for cervical radiculopathy caused by disk herniation. DESIGN: Single-center, prospective, consecutive case series. SETTING: A single large academic institution. PATIENTS: A total of 11 patients with radiculopathic pain and magnetic resonance imaging findings positive for disk herniation elected to undergo single-level cervical diskectomy. METHODS OR INTERVENTIONS: Lavage was performed by needle injection and aspiration upon entering the disk space for fluoroscopic localization before diskectomy. MAIN OUTCOME MEASUREMENTS: The lavage fluid was assayed for pH and the FAC, as well as for the cytokines interleukin-6 (IL-6), interferon-γ, monocyte chemotactic protein (MCP), and macrophage inhibitory protein-1ß. RESULTS: The subjects were 7 women and 4 men with a mean age of 50.6 years (SE 9.7; range, 36-70 years). The mean concentrations (SE; range) in picograms per milliliter were 7.9 (4.4; 0-44) for IL-6, 25.3 (15.5; 0-159) for interferon-γ, 16.1 (11.9; 0-121) for MCP, and 6.1 (2.8; 0-29) for macrophage inhibitory protein-1ß. The optical density of the FAC at 450 nm was 0.151 (0.036; 0.1-0.32), and the pH was 6.68 (0.1; 6.10-7.15). Statistically significant correlations were found between MCP and FAC (P = .036) and between FAC and pH (P = .008). CONCLUSIONS: Biochemical analysis of injured cervical intervertebral disks reveals the presence of inflammatory markers such as MCP, fragments of structural matrix proteins such as FAC, and a correlation with pH. Further evaluation of the FAC as a potential diagnostic biomarker or therapeutic target is warranted in the cervical spine.