Faculty Bibliography

Objective: The present randomized controlled trial compared arthrocentesis of the effusive knee followed by corticosteroid injection performed by the conventional anatomic landmark palpation-guided technique to the same procedure performed with ultrasound (US) needle guidance. Methods: Sixty-four palpably effusive knees were randomized to (i) palpation-guided arthrocentesis with a conventional 20-mL syringe (22 knees), (ii) US-guided arthrocentesis with a 25-mL reciprocating procedure device (RPD) mechanical aspirating syringe (22 knees), or (iii) US-guided arthrocentesis with a 60-mL automatic aspirating syringe (20 knees). The one-needle two-syringe technique was used. Outcome measures included patient pain by the Visual Analogue Scale (VAS) for pain (0-10 cm), the proportion of diagnostic samples, synovial fluid volume yield, complications, and therapeutic outcome at 2 weeks. Results: Sonographic guidance resulted in 48% less procedural pan (VAS; palpation-guided: 5.8 +/- 3.0 cm, US-guided: 3.0 +/- 2.8 cm, p < 0.001), 183% increased aspirated synovial fluid volumes (palpation-guided: 12 +/- 10 mL, US-guided: 34 +/- 25 mL, p < 0.0001), and improved outcomes at 2 weeks (VAS; palpation-guided: 2.8 +/- 2.4 cm, US-guided: 1.5 +/- 1.9 cm, p = 0.034). Outcomes of sonographic guidance with the mechanical syringe and automatic syringe were comparable in all outcome measures. Conclusions: US-guided arthrocentesis and injection of the knee are superior to anatomic landmark palpation-guided arthrocentesis, resulting in significantly less procedural pain, improved arthrocentesis success, greater synovial fluid yield, more complete joint decompression, and improved clinical outcomes.

Although intraarticular injections are important to the management of rheumatoid arthritis, there are few studies regarding the cost-effectiveness of alternative injection techniques. This randomized controlled study addressed the cost-effectiveness of two different low-cost, anatomic landmark palpation-directed intraarticular injection techniques. Ninety-six symptomatic rheumatoid knees were randomized to two different low-cost, palpation-guided intraarticular injection techniques utilizing (1) a conventional syringe or (2) a mechanical syringe, the RPD (the reciprocating procedure device). Three milliliters of 1% lidocaine were used to anesthetize the synovial membrane, followed by arthrocentesis and hydrodissection, and injection of 80 mg of triamcinolone acetonide utilizing the one-needle two-syringe technique. Baseline pain, procedural pain, aspirated fluid volume, pain at outcome (2 weeks and 6 months), responders, reinjection rates, cost/patient/year, and cost/responder/year were determined. Pain was measured with the 10 cm Visual Analogue Pain Scale (VAS). Both techniques significantly reduced pain scores at outcome from baseline (P < 0.001). The mechanical syringe technique resulted in a greater volume of aspirated fluid (P < 0.01), a 38% reduction in procedural pain (P < 0.001), a 24% reduction in pain scores at outcome (P < 0.03), an increase in the responder rate (P < 0.025), 33% increase in the time to next injection (P < 0.001), 23% ($35 US) reduction in cost/patient/year for a patient treated in a physician office (P < 0.001), 24% reduction ($26 US) in cost/patient/year for a hospital outpatient (P < 0.001), and 51% ($151 US) reduction in cost/responder/year (P < 0.001). The outcomes and cost-effectiveness of intraarticular injection of the rheumatoid knee can be improved significantly with low-cost alternations in technique.

OBJECTIVE: The present randomized controlled study investigated whether sonographic needle guidance affected the outcomes of intra-articular injection for osteoarthritis of the knee. METHODS: Ninety-four noneffusive knees with osteoarthritis were randomized to injection by conventional palpation-guided anatomic landmark injection or sonographic image-guided injection enhanced with a 1-handed mechanical (the reciprocating procedure device) syringe. After intra-articular placement and synovial space dilation were confirmed by sonography, a syringe exchange was performed, and 80 mg of triamcinolone acetonide was injected with the second syringe through the indwelling intra-articular needle. Baseline pain, procedural pain, pain at outcome (2 weeks and 6 months), responders, therapeutic duration, reinjection rates, total cost, and cost per responder were determined. RESULTS: Relative to conventional palpation-guided anatomic landmark methods, sonographic guidance for injection of the knee resulted in 48% reduction in procedural pain (P < 0.001), a 42% reduction in pain scores at outcome (P < 0.03), 107% increase in the responder rate (P < 0.001), 52% reduction in the nonresponder rate (P < 0.001), a 36% increase in therapeutic duration (P = 0.01), a 13% reduction ($17) in cost per patient per year, and a 58% ($224) reduction in cost per responder per year for a hospital outpatient (P < 0.001). CONCLUSIONS: Sonographic needle guidance reduced procedural pain and improved the clinical outcomes and cost-effectiveness of intra-articular injections of the osteoarthritic knee

BACKGROUND: The American Academy of Orthopaedic Surgery (AAOS), The Joint Commission, the Occupational Safety and Health Administration (OSHA), and the Needlestick Safety and Prevention Act encourage the integration of safety-engineered devices to prevent needlestick injuries to health-care workers and patients. We hypothesized that safety syringes and needles could be used in outpatient orthopaedic injection and aspiration procedures. METHODS: The study investigated the orthopaedic uses and procedural idiosyncrasies of safety-engineered devices, including (1) four safety needles (Eclipse, SafetyGlide, SurGuard, and Magellan), (2) a mechanical safety syringe (RPD), (3) two automatic retractable syringes (Integra, VanishPoint), (4) three manual retractable syringes (Procedur-SF, Baksnap, Invirosnap), and (5) three shielded syringes (Safety-Lok, Monoject, and Digitally Activated Shielded [DAS] Syringe). The devices were first tested ex vivo, and then 1300 devices were used for 425 subjects undergoing outpatient arthrocentesis, intra-articular injections, local anesthesia, aspiration biopsy, and ultrasound-guided procedures. RESULTS: During the clinical observation, there were no accidental needlesticks (0 needlesticks per 1300 devices). Safety needles could be successfully used on a Luer syringe but were limited to =1.5 in (=3.81 cm) in length and the shield could interfere with sonography. The mechanical safety syringes functioned well in all orthopaedic procedures. Automatic retractable syringes were too small for arthrocentesis of the knee, and the plunger blew out and prematurely collapsed with high-pressure injections. The manual retractable syringes and shielded syringes could be used with conventional needles for most orthopaedic procedures. CONCLUSIONS: The most effective and reliable safety devices for orthopaedic syringe procedures are shielded safety needles, mechanical syringes, manual retractable syringes, and shielded syringes, but not automatic retractable syringes. Even when adopting safety-engineered devices for an orthopaedic clinic, conventional syringes larger than 20 mL and conventional needles longer than 1.5 in (3.8 cm) are necessary. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence

BACKGROUND: The extended knee lateral midpatellar portal for intraarticular injection of the knee is accurate but is not practical for all patients. We hypothesized that a modified anteriolateral portal where the synovial membrane of the medial femoral condyle is the target would be highly accurate and effective for intraarticular injection of the knee. METHODS: 83 subjects with non-effusive osteoarthritis of the knee were randomized to intraarticular injection using the modified anteriolateral bent knee versus the standard lateral midpatellar portal. After hydrodissection of the synovial membrane with lidocaine using a mechanical syringe (reciprocating procedure device), 80 mg of triamcinolone acetonide were injected into the knee with a 2.0-in (5.1-cm) 21-gauge needle. Baseline pain, procedural pain, and pain at outcome (2 weeks and 6 months) were determined with the 10 cm Visual Analogue Pain Score (VAS). The accuracy of needle placement was determined by sonographic imaging. RESULTS: The lateral midpatellar and anteriolateral portals resulted in equivalent clinical outcomes including procedural pain (VAS midpatellar: 4.6 +/- 3.1 cm; anteriolateral: 4.8 +/- 3.2 cm; p = 0.77), pain at outcome (VAS midpatellar: 2.6 +/- 2.8 cm; anteriolateral: 1.7 +/- 2.3 cm; p = 0.11), responders (midpatellar: 45%; anteriolateral: 56%; p = 0.33), duration of therapeutic effect (midpatellar: 3.9 +/- 2.4 months; anteriolateral: 4.1 +/- 2.2 months; p = 0.69), and time to next procedure (midpatellar: 7.3 +/- 3.3 months; anteriolateral: 7.7 +/- 3.7 months; p = 0.71). The anteriolateral portal was 97% accurate by real-time ultrasound imaging. CONCLUSION: The modified anteriolateral bent knee portal is an effective, accurate, and equivalent alternative to the standard lateral midpatellar portal for intraarticular injection of the knee. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00651625.

Non-toxic derivatives of botulinum neurotoxin A (BoNT/A) have potential use as neuron-targeting delivery vehicles, and as reagents to study intracellular trafficking. We have designed and expressed an atoxic derivative of BoNT/A (BoNT/A ad) as a full-length 150 kDa molecule consisting of a 50 kDa light chain (LC) and a 100 kDa heavy chain (HC) joined by a disulfide bond and rendered atoxic through the introduction of metalloprotease-inactivating point mutations in the light chain. Studies in neuronal cultures demonstrated that BoNT/A ad cannot cleave synaptosomal-associated protein 25 (SNAP25), the substrate of wt BoNT/A, and that it effectively competes with wt BoNT/A for binding to endogenous neuronal receptors. In vitro and in vivo studies indicate accumulation of BoNT/A ad at the neuromuscular junction of the mouse diaphragm. Immunoprecipitation studies indicate that the LC of BoNT/A ad forms a complex with SNAP25 present in the neuronal cytosolic fraction, demonstrating that the atoxic LC retains the SNAP25 binding capability of the wt toxin. Toxicity of BoNT/A ad was found to be reduced approximately 100,000-fold relative to wt BoNT/A

OBJECTIVE: We studied whether sonographic needle guidance affected the outcomes of intraarticular (IA) injection for inflammatory arthritis. METHODS: Joints with inflammatory arthritis (n = 244; 76% rheumatoid arthritis, 3% small joints, 51% intermediate, and 46% large) were randomized to injection by conventional palpation-guided anatomic injection (120 joints) or sonographic image-guided injection enhanced with a 1-handed reciprocating procedure device mechanical syringe (124 joints). A 1-needle, 2-syringe technique was used. After IA placement and synovial space dilation were confirmed by sonography, a syringe exchange was performed, and triamcinolone acetonide was injected with the second syringe through the indwelling IA needle. Baseline pain, procedural pain, pain at outcome (2 weeks and 6 months), responders, therapeutic duration, reinjection rates, total cost, and cost per responder were determined. RESULTS: Relative to conventional palpation-guided methods, sonographic guidance for injection of inflammatory arthritis resulted in an 81% reduction in injection pain (p < 0.001), 35% reduction in pain scores at outcome (p < 0.02), 38% increase in the responder rate (p < 0.003), 34% reduction in the non-responder rate (p < 0.003), 32% increase in therapeutic duration (p = 0.01), 8% reduction ($7) in cost/patient/year, and a 33% ($64) reduction in cost/responder/year for a hospital outpatient (p < 0.001). CONCLUSION: Sonographic needle guidance improves the performance, clinical outcomes, and cost-effectiveness of IA injections for inflammatory arthritis. (Clinical Trial Identifier NCT00651625)

Work from multiple laboratories has clarified how the structural domains of botulinum neurotoxin A (BoNT/A) disable neuronal exocytosis, but important questions remain unanswered. Because BoNT/A intoxication disables its own uptake, light chain (LC) does not accumulate in neurons at detectable levels. We have therefore designed, expressed and purified a series of BoNT/A atoxic derivatives (ad) that retain the wild type features required for native trafficking. BoNT/A1ad(ek) and BoNT/A1ad(tev) are full length derivatives rendered atoxic through double point mutations in the LC protease (E(224)>A; Y(366)>A). DeltaLC-peptide-BoNT/A(tev) and DeltaLC-GFP-BoNT/A(tev) are derivatives wherein the catalytic portion of the LC is replaced with a short peptide or with GFP plus the peptide. In all four derivatives, we have fused the S6 peptide sequence GDSLSWLLRLLN to the N-terminus of the proteins to enable site-specific attachment of cargo using Sfp phosphopantetheinyl transferase. Cargo can be attached in a manner that provides a homogeneous derivative population rather than a polydisperse mixture of singly and multiply-labeled molecular species. All four derivatives contain an introduced cleavage site for conversion into disulfide-bonded heterodimers. These constructs were expressed in a baculovirus system and the proteins were secreted into culture medium and purified to homogeneity in yields ranging from 1 to 30 mg per liter. These derivatives provide unique tools to study toxin trafficking in vivo, and to assess how the structure of cargo linked to the heavy chain (HC) influences delivery to the neuronal cytosol. Moreover, they create the potential to engineer BoNT-based molecular vehicles that can target therapeutic agents to the neuronal cytoplasm