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Total knee arthroplasty (TKA) is frequently associated with severe, prolonged postsurgical pain, and therefore local anesthetic-based peripheral nerve blocks are commonly used for postoperative analgesia. Cryoneurolysis involves the use of freezing temperatures to provide a reversible sensory (and motor) block with a duration measured in weeks and months, more commensurate with the typical period of post-TKA pain. We therefore conducted a randomized controlled pilot study to evaluate the use of this modality for the treatment of pain following TKA to (1) determine the feasibility of and optimize the study protocol for a subsequent definitive clinical trial; and (2) estimate analgesia and opioid reduction within the first 3 postoperative weeks.A convenience sample of 16 patients undergoing primary TKA with a single-injection and/or continuous adductor canal nerve block were randomized to receive either active cryoneurolysis or a sham procedure targeting the infrapatellar branch of the saphenous nerve, in a participant-masked fashion. This was a pilot study with a relatively small number of participants, and therefore resulting data were not analyzed statistically.Compared with participants receiving sham, the active treatment group reported slightly lower average and worst pain scores as well as opioid consumption and sleep disturbances due to pain at a majority of postoperative time points between postoperative days (POD) 4-21.Preoperative ultrasound-guided cryoneurolysis of the infrapatellar branch of the saphenous nerve is feasible and may provide analgesic benefits for multiple weeks following TKA. A definitive randomized controlled trial appears warranted.

BackgroundThere are few effective pain treatments following trauma on the battlefield other than opioids, which are limited by respiratory depression. Ultrasound-guided percutaneous peripheral nerve stimulation ("neuromodulation") has been proposed as an analgesic, but requires physician-level skills, advanced equipment, and an hour to administer. In contrast, percutaneous auricular neuromodulation may be placed by a medic in the field under nonsterile conditions in a few minutes, theoretically provides analgesia for any anatomic location, has no side effects, and no significant risks. It therefore offers the potential to be applied quickly on the battlefield without any of the limitations of opioids. We propose total joint replacement as a surrogate for battlefield trauma and here present a case report to demonstrate proof of concept.MethodsFollowing open total knee or hip arthroplasty under spinal anesthesia, two patients had an auricular neuromodulation device applied within the recovery room. Patients were discharged with the unit and contacted daily for 7 days.ResultsThe devices were each applied in under 3 minutes without difficulty, were well tolerated during use, and removed without complication at home on Day 5. During use, neither patient experienced pain while lying, sitting, or ambulating. Neither required analgesics other than scheduled celecoxib; and a single tablet (50 mg) of tramadol for one patient on postoperative Days 3 and 4 for pain while lowering herself to a seated position. On Days 6 and 7, both patients experienced an increase in pain, one of whom required around-the-clock tramadol.ConclusionAmbulatory postoperative percutaneous auricular neuromodulation is feasible. In these two cases, it appears to have markedly reduced pain scores and opioid requirements free of systemic side effects during the week following major orthopedic surgery. Considering the potential of this modality to treat trauma on the battlefield without systemic side effects, additional investigation appears warranted.Level of evidenceTherapeutic/care management; Level V.

We present a case series to demonstrate proof-of-concept for the off-label use of an auricular neuromodulation device-originally developed to treat symptoms associated with opioid withdrawal-to instead provide analgesia and opioid-sparing following knee and hip arthroplasties. Within the recovery room, an auricular neuromodulation device (near-field stimulator system 2 [NSS-2] Bridge, Masimo) was applied to 5 patients. Average daily pain at rest and while moving was a median of 0 to 2 as measured on the 0 to 10 numeric rating scale, while median daily oxycodone use was 0 to 2.5 mg until device removal at home on postoperative day 5. One patient avoided opioid use entirely.

Orthopedic trauma is a significant military problem, causing several of the most disabling conditions with high rates of separation from duty and erosion of military readiness. The objective of this report is to summarize the findings of case series of a non-opioid therapy—percutaneous peripheral nerve stimulation (PNS) – and describe its potential for postoperative analgesia, early opioid cessation, and improved function following orthopedic trauma. Percutaneous PNS has been evaluated for the treatment of multiple types of pain, including two case series on postoperative pain following total knee replacement (n = 10 and 8, respectively) and a case series on postamputation pain (n = 9). The orthopedic trauma induced during TKR is highly representative of multiple types of orthopedic trauma sustained by Service members and frequently produces intense, prolonged postoperative pain and extended opioid use following surgery. Collectively, the results of these three clinical studies demonstrated that percutaneous PNS can provide substantial pain relief, reduce opioid use, and improve function. These outcomes suggest that there is substantial potential for the use of percutaneous PNS following orthopedic trauma.

Biologically augmented surgical treatments of orthopaedic conditions are increasingly popular. Bone marrow aspirate concentrate is a key orthobiologic tissue source, and the field is moving from the standard iliac crest marrow aspiration toward local aspirations of marrow depots that are accessible during the standard-of-care procedures in an attempt to reduce morbidity, surgery time, and cost. Here, we present the aspiration of the standard iliac marrow depot, but through a novel acetabular approach during total hip arthroplasty. This procedure markedly simplifies biologic augmentation with bone marrow aspirate concentrate in this large patient cohort.

Background: There is a need to identify and quantify mesenchymal stromal cells (MSCs) in human bone marrow aspirate concentrate (BMAC) source tissues, but current methods to do so were established in cultured cell populations. Given that surface marker and gene expression change in cultured cells, it is doubtful that these strategies are valid to quantify MSCs in fresh BMAC. Purpose: To establish the presence, quantity, and heterogeneity of BMAC-derived MSCs in minimally manipulated BMAC using currently available strategies. Study Design: Descriptive laboratory study. Methods: Five published strategies to identify MSCs were compared for suitability and efficiency to quantify clinical-grade BMAC-MSCs and cultured MSCs at the single cell transcriptome level on BMAC samples being used clinically from 15 orthopaedic patients and on 1 cultured MSC sample. Strategies included (1) the guidelines by the International Society for Cellular Therapy (ISCT), (2) CD271 expression, (3) the Ghazanfari et al transcriptional profile, (4) the Jia et al transcriptional profile, and (5) the Silva et al transcriptional profile. Results: ISCT guidelines did not identify any MSCs in BMAC at the transcriptional level and only 1 in 9 million cells at the protein level. Of 12,850 BMAC cells, 9 expressed the CD271 gene. Only 116 of 396 Ghazanfari genes were detected in BMAC, whereas no cells expressed all of them. No cells expressed all Jia genes, but 25 cells expressed at least 13 of 22. No cells expressed all Silva genes, but 19 cells expressed at least 8 of 23. Most importantly, the liberalized strategies tended to identify different cells and most of them clustered with immune cells. Conclusion: Currently available methods need to be liberalized to identify any MSCs in fresh human BMAC and lack consensus at the single cell transcriptome and protein expression levels. These different cells should be isolated and challenged to establish phenotypic differences. Clinical Relevance: This study demonstrated that improved strategies to quantify MSC concentrations in BMAC for clinical applications are urgently needed. Until then, injected minimally manipulated MSC doses should be reported as rough estimates or as unknown.

While obesity and insulin resistance are known risk factors for wound complications after total joint arthroplasty (TJA), the biologic causes remain to be elucidated. Recently, neutrophil extracellular trap formation (NETosis) was identified as a mediator of delayed wound healing in insulin resistant states. Herein, we explored the relationship between obesity, insulin resistance and biomarkers of NET formation in TJA subjects. We enrolled 14 obese (body mass index [BMI]≥30 kg/m2), and 15 lean (BMI2) subjects undergoing primary knee or hip TJA. On the day of surgery, skeletal muscle proximal to the operated joint and plasma were collected. Protein abundance of NETosis biomarkers, peptidylarginine deaminase 4 (PAD4) and neutrophil elastase (NE) were assessed in skeletal muscle by immunoblotting and metabolic parameters (glucose, insulin, triglycerides, free fatty acids) and cell-free double-stranded DNA (cf-dsDNA) were assessed in plasma and were correlated with obesity and insulin resistance (as measured by the homeostatic model assessment for insulin resistance). When comparing lean and obese subjects, there were no significant differences in plasma cf-dsDNA or skeletal muscle NE or PAD4 abundance. In contrast, skeletal muscle PAD4 abundance, but not NE or plasma cf-dsDNA, was positively correlated with insulin resistance. Compared to insulin sensitive subjects, insulin resistant TJA subjects have higher expression of PAD4 at the surgical site and therefore may have higher rates of NET formation, which may lead to delayed surgical site wound healing.

Background Obesity is prevalent among patients undergoing total hip arthroplasty and has been associated with the risk of wound complications, particularly when an anterior approach is used. However, most studies have focused on obesity defined by the body mass index (BMI), without considering the metabolic effects of adiposity. Thus, in this study, we investigated the independent effects of the BMI and metabolic syndrome on wound complications after total hip arthroplasty. Methods Among 804 consecutive patients undergoing total hip arthroplasty between October 2013 and July 2016, we evaluated the associations between obesity (BMI ≥30 mg/kg2), metabolic syndrome (defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines), and wound complication (defined as documented wound dehiscence, drainage, erythema, hematoma, infection, or seroma) over a 1-year follow-up period. We used Cox proportional hazards models adjusting for demographics, smoking status, and hospital length of stay. Results Patients’ mean age at time of surgery was 62.0 ± 11.9 years. Forty-seven percent were male, 27.9% were obese, and 11.6% met the definition for metabolic syndrome. Metabolic syndrome was associated with a 4-fold higher risk of wound complication (95% confidence interval: 1.4-11.1) after adjusting for all covariates including the BMI. In unadjusted analysis, obesity was associated with a higher risk of wound complication (hazard ratio: 2.8, 95% confidence interval: 1.3-6.2). However, obesity was not associated with the risk of wound complication after adjusting for the metabolic syndrome (P = .16). Conclusions Metabolic syndrome, but not obesity, defined by a BMI ≥30, was associated with wound complications, suggesting that metabolic effects of adiposity may represent a distinct risk factor in the development of wound complications from a higher BMI alone.

BACKGROUND:A continuous adductor canal block provides analgesia after surgical procedures of the knee. Recent neuroanatomic descriptions of the thigh and knee led us to speculate that local anesthetic deposited in the distal thigh close to the adductor hiatus would provide superior analgesia compared to a more proximal catheter location. We therefore tested the hypothesis that during a continuous adductor canal nerve block, postoperative analgesia would be improved by placing the perineural catheter tip 2-3 cm cephalad to where the femoral artery descends posteriorly to the adductor hiatus (distal location) compared to a more proximal location at the midpoint between the anterior superior iliac spine and the superior border of the patella (proximal location). METHODS:Preoperatively, subjects undergoing total knee arthroplasty received an ultrasound-guided perineural catheter inserted either in the proximal or distal location within the adductor canal in a randomized, subject-masked fashion. Subjects received a single injection of lidocaine 2% via the catheter preoperatively, followed by an infusion of ropivacaine 0.2% (8 mL/h basal, 4 mL bolus, 30 minutes lockout) for the study duration. After joint closure, the surgeon infiltrated the entire joint using 30 mL of ropivacaine (0.5%), ketorolac (30 mg), epinephrine (5 μg/mL), and tranexamic acid (2 g). The primary end point was the median level of pain as measured on a numeric rating scale (NRS) during the time period of 8:00 AM to 12:00 PM the day after surgery. RESULTS:For the primary end point, the NRS of subjects with a catheter inserted at the proximal location (n = 24) was a median (10th, 25th-75th, 90th quartiles) of 0.5 (0.0, 0.0-3.2, 5.0) vs 3.0 (0.0, 2.0-5.4, 7.8) for subjects with a catheter inserted in the distal location (n = 26; P = .011). Median and maximum NRSs were lower in the proximal group at all other time points, but these differences did not reach statistical significance. There were no clinically relevant or statistically significant differences between the treatment groups for any other secondary end point, including opioid consumption and ambulation distance. CONCLUSIONS:For continuous adductor canal blocks accompanied by intraoperative periarticular local anesthetic infiltration, analgesia the day after knee arthroplasty is improved with a catheter inserted at the level of the midpoint between the anterior superior iliac spine and the superior border of the patella compared with a more distal insertion closer to the adductor hiatus.

Background: The relative analgesic requirements for tricompartmental (TKA) and unicompartmental (UKA) knee arthroplasty and their effects on discharge readiness remain unexamined when continuous adductor canal and femoral nerve blocks are used for analgesia in the immediate postoperative period. Methods: Data were collected from 2 previously-published clinical trials involving subjects undergoing TKA (n=79) or UKA (n=30) randomized to either an adductor canal or femoral perineural catheter and ropivacaine 0.2% infusion for 2 (UKA) or 3 (TKA) days. Originally, we compared each catheter location (adductor vs. femoral) while holding surgical procedure constant (comparing solely TKAs and solely UKAs). We now compare type of surgical procedure (TKA vs UKA) while holding catheter location (adductor vs. femoral) constant. The primary outcome was the time to attain 4 discharge criteria including pain, opioid requirements, and ambulation/mobilization. Results: For adductor canal catheters, UKA patients reached all 4 discharge criteria in 35 [24—43] hours which was significantly faster than those given TKA who took 55 [43—63] hours (difference: 18h; 95%CI 9 to 28 h; P

Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

Background: The authors conducted a randomized, controlled, parallel-arm, superiority study to test the hypothesis that a continuous adductor canal block decreases the time to attain four discharge criteria compared with a continuous femoral nerve block after tricompartment knee arthroplasty. Methods: Subjects undergoing tricompartment knee arthroplasty were randomized using computer-generated lists to either an adductor canal or femoral perineural catheter (3-day ropivacaine 0.2% infusion) in an unmasked manner. The primary outcome was the time to attain four criteria: (1) adequate analgesia; (2) intravenous opioids independence; (3) ability to stand, walk 3 m, return, and sit down; and (4) ambulate 30 m. Results: Subjects with an adductor canal catheter (n = 39) reached all four criteria in a median of 55 h (interquartile, 42 to 63 h) compared with 61 h (49 to 69 h) for those with a femoral catheter (n = 41; 95% CI, −13 to 1 h; P = 0.12). The percentage of subjects who reached the two mobilization criteria on postoperative days 1 and 2 were 72 and 95% for those with an adductor canal catheter (n = 39), but only 27 and 76% in subjects with a femoral catheter (n = 41; both P < 0.001). Differences in pain scores at rest and intravenous opioid requirements were minimal, but femoral infusion improved dynamic analgesia (P = 0.01 to 0.02). Conclusion: Compared with a continuous femoral nerve block, a continuous adductor canal block did not appreciably decrease the time to overall discharge readiness even though it did decrease the time until adequate mobilization, primarily because both groups experienced similar analgesia and intravenous opioid requirements that—in most cases—exceeded the time to mobilization.

Author(s): Ilfeld, Brian M; Ball, Scott T; Gabriel, Rodney A; Sztain, Jacklynn F; Monahan, Amanda M; Abramson, Wendy B; Khatibi, Bahareh; Said, Engy T; Parekh, Jesal; Grant, Stuart A; Wongsarnpigoon, Amorn; Boggs, Joseph W | Abstract: IntroductionThe objective of the present feasibility study was to investigate the use of a new treatment modality-percutaneous peripheral nerve stimulation (PNS)-in controlling the often severe and long-lasting pain following total knee arthroplasty (TKA).MethodsFor patients undergoing a primary, unilateral TKA, both femoral and sciatic open-coil percutaneous leads (SPR Therapeutics, Cleveland, OH) were placed up to seven days prior to surgery using ultrasound guidance. The leads were connected to external stimulators and used both at home and in the hospital for up to six weeks total.ResultsIn six of seven subjects (86%), the average of daily pain scores across the first two weeks was l4 on the 0-10 Numeric Rating Scale for pain. A majority of subjects (four out of seven; 57%) had ceased opioid use within the first week (median time to opioid cessation for all subjects was six days). Gross sensory/motor function was maintained during stimulation, enabling stimulation during physical therapy and activities of daily living. At 12 weeks following surgery, six of seven subjects had improved by g10% on the Six-Minute Walk Test compared to preoperative levels, and WOMAC scores improved by an average of 85% compared to before surgery. No falls, motor block, or lead infections were reported.ConclusionsThis feasibility study suggests that for TKA, ultrasound-guided percutaneous PNS is feasible in the immediate perioperative period and may provide analgesia without the undesirable systemic effects of opioids or quadriceps weakness induced by local anesthetics-based peripheral nerve blocks.

Combined scientific advances in pharmaceutical agents, perineural blocks, and pump delivery capabilities such as those used with continuous peripheral nerve blocks have demonstrated advantages in pain management for patients undergoing joint arthroplasty. This report documents the incidence of falls increased after the implementation of a continuous peripheral nerve block program for patients undergoing knee and hip arthroplasty in an academic medical center.

The repair of articular defects with use of osteochondral allografts ideally restores the structure, function, and biology of the cartilage surface. Allograft efficacy may be dependent on sufficient chondrocyte metabolism to preserve cartilage homeostasis and prevent degeneration. Fresh osteochondral allografts are typically implanted with high chondrocyte viability, and retrieved grafts have contained viable chondrocytes up to twenty-nine years after implantation1-5. In contrast, frozen osteochondral allografts, used for massive oncologic joint reconstructions, have low chondrocyte viability at implantation, and grafts retrieved at approximately one to five years contain acellular and often degenerate cartilage6,7. Attempts at future improvements in the application of osteochondral allografts would benefit from an understanding of how the allograft implantation state affects defect repair efficacy and the mechanisms of cartilage maintenance with the best (fresh) and worst (frozen) conditions of cartilage within allografts. Animal models allow for a systematic and temporal evaluation of cartilage repair and remodeling. Data obtained from human allograft retrievals are skewed toward poor outcomes, since analysis is performed on “failed” cases, where revision or conversion to total joint arthroplasty was required5,8,9. Clinical evaluations based on patient satisfaction and often limited by availability for long-term follow-up are not sensitive to early stage degeneration. Intradisciplinary and multiscale analyses of cartilage repair in animal models may elucidate the types of tissue changes that are indicative of early stage degeneration and may provide insight into the time course of cartilage remodeling and/or deterioration. Results from such animal models suggest that postoperative time is an important determinant of the quality of cartilage repair. Frozen allografts appear grossly normal and similar to fresh allografts at short postoperative durations of as long as three months10-13, and then they appear discolored and roughened, often exposing subchondral bone, at eleven to twelve months12-15. In contrast, cartilage of fresh allografts remains grossly normal for as long as twelve months, with only mild degenerative changes14-16. Gross observations are paralleled by histopathologic changes, including reduced (for frozen) and maintained (for fresh) safranin-O staining intensity10-21. Cartilage cellularity and load-bearing function have been analyzed in relatively few studies. Qualitatively, frozen allografts appear acellular by three months, compared with fresh allografts, which contain viable cells for as long as twelve months12-16. When compared with that in the nonoperative control knees, the confined compressive stiffness of the operatively treated knees was slightly reduced in the fresh allograft areas, and markedly reduced in the frozen allograft areas with increasing postoperative duration12,13,15,19,20. The reduction of cartilage load-bearing function was associated with proteoglycan content15; however, other determinants of cartilage stiffness have not been investigated. Rapid indentation testing of cartilage, which is sensitive to structural measures of cartilage degeneration22, may be useful to elucidate mechanisms of allograft deterioration or maintenance. Large-animal studies with frozen or fresh allografts at moderate time points (between three and eleven months) are needed to understand the progression of articular cartilage deterioration. The hypothesis of this study was that the state of the allograft at implantation affects its performance after six months in vivo. The specific aim was to determine the effect of allograft treatment (frozen or fresh) on the properties of articular cartilage from retrieved osteochondral allografts at six months in the goat model by assessing cartilage function, zonal composition, and structure. The results of this study suggest that the use of a systematic approach as discussed in this paper, including a detailed baseline analysis at six months, may aid in the evaluation of in vivo cartilage restoration.

Background Hip arthroplasty frequently requires potent postoperative analgesia, often provided with an epidural or posterior lumbar plexus local anesthetic infusion. However, American Society of Regional Anesthesia guidelines now recommend against epidural and continuous posterior lumbar plexus blocks during administration of various perioperative anticoagulants often administered after hip arthroplasty. A continuous femoral nerve block is a possible analgesic alternative, but whether it provides comparable analgesia to a continuous posterior lumbar plexus block after hip arthroplasty remains unclear. We therefore tested the hypothesis that differing the catheter insertion site (femoral versus posterior lumbar plexus) after hip arthroplasty has no impact on postoperative analgesia. Methods Preoperatively, subjects undergoing hip arthroplasty were randomly assigned to receive either a femoral or a posterior lumbar plexus stimulating catheter inserted 5 to 15 cm or 0 to 1 cm past the needle tip, respectively. Postoperatively, patients received perineural ropivacaine, 0.2% (basal 6 mL/hr, bolus 4 mL, 30-minute lockout) for at least 2 days. The primary end point was the average daily pain scores as measured with a numeric rating scale (0-10) recorded in the 24-hour period beginning at 07:30 the morning after surgery, excluding twice-daily physical therapy sessions. Secondary end points included pain during physical therapy, ambulatory distance, and supplemental analgesic requirements during the same 24-hour period, as well as satisfaction with analgesia during hospitalization. Results The mean (SD) pain scores for subjects receiving a femoral infusion (n = 25) were 3.6 (1.8) versus 3.5 (1.8) for patients receiving a posterior lumbar plexus infusion (n = 22), resulting in a group difference of 0.1 (95% confidence interval -0.9 to 1.2; P = 0.78). Because the confidence interval was within a prespecified -1.6 to 1.6 range, we conclude that the effect of the 2 analgesic techniques on postoperative pain was equivalent. Similarly, we detected no differences between the 2 treatments with respect to the secondary end points, with one exception: subjects with a femoral catheter ambulated a median (10th-90th percentiles) 2 (0-17) m the morning after surgery, in comparison with 11 (0-31) m for subjects with a posterior lumbar plexus catheter (data nonparametric; P = 0.02). Conclusions After hip arthroplasty, a continuous femoral nerve block is an acceptable analgesic alternative to a continuous posterior lumbar plexus block when using a stimulating perineural catheter. However, early ambulatory ability suffers with a femoral infusion.

Resurfacing systems use press-fit, monoblock, cobalt chrome alloy acetabular sockets because of the material's ability to withstand stresses while accommodating a large femoral head. Despite the widespread use of these types of sockets for both hip resurfacing and total hip replacement, there is a paucity of literature assessing the outcomes of these cups in particular. The 10 year survivorship of the Conserve® Plus monoblock acetabular component used in this study was 98.3% with small pelvic osteolytic lesions suspected in only 2.3%. This study highlights the excellent radiographic survivorship profile of the Conserve® Plus socket.

Background: Previously, we have demonstrated that extending a continuous femoral nerve block (cFNB) from overnight to 4 days after total knee arthroplasty (TKA) provides clear benefits during the infusion, but not subsequent to catheter removal. However, there were major limitations in generalizing the results of that investigation, and we subsequently performed a very similar study using a multicenter format, with many health care providers, in patients on general orthopedic wards, thus greatly improving inference of the results to the general population. Not surprisingly, the perioperative/short-term outcomes differed greatly from the first, more limited study. We now present a prospective follow-up study of the previously published, multicenter, randomized controlled clinical trial to investigate the possibility that an extended ambulatory cFNB decreases long-term pain, stiffness, and functional disability after TKA, which greatly improves inference of the results to the general population. Methods: Subjects undergoing TKA received a cFNB with ropivacaine 0.2% from surgery until the following morning, at which time patients were randomized to continue either perineural ropivacaine (n = 28) or normal saline (n = 26). Patients were discharged with their catheter and a portable infusion pump, and catheters were removed on postoperative day 4. Health-related quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis Index preoperatively and then at 7 days, as well as 1, 2, 3, 6, and 12 months after surgery. This index evaluates pain, stiffness, and physical functional disability. For inclusion in the analysis, we required a minimum of 4 of the 6 time points, including day 7 and at least 2 of months 3, 6, and 12. Results: The 2 treatment groups had similar Western Ontario and McMaster Universities Osteoarthritis scores for the mean area-under-the-curve calculations (point estimate for the difference in mean area under the curve for the 2 groups [overnight infusion group − extended infusion group] = 3.8; 95% confidence interval, −3.8 to +11.3; P = 0.32) and at all individual time points (P > 0.05). Conclusions: This investigation found no evidence that extending an overnight cFNB to 4 days improves (or worsens) subsequent pain, stiffness, or physical function after TKA in patients of multiple centers convalescing on general orthopedic wards.

Background The main determinant of continuous peripheral nerve block effects--local anesthetic concentration and volume or simply total drug dose--remains unknown. Methods We compared two different concentrations and basal rates of ropivacaine--but at equivalent total doses--for continuous posterior lumbar plexus blocks after hip arthroplasty. Preoperatively, a psoas compartment perineural catheter was inserted. Postoperatively, patients were randomly assigned to receive perineural ropivacaine of either 0.1% (basal 12 ml/h, bolus 4 ml) or 0.4% (basal 3 ml/h, bolus 1 ml) for at least 48 h. Therefore, both groups received 12 mg of ropivacaine each hour with a possible addition of 4 mg every 30 min via a patient-controlled bolus dose. The primary endpoint was the difference in maximum voluntary isometric contraction (MVIC) of the ipsilateral quadriceps the morning after surgery, compared with the preoperative MVIC, expressed as a percentage of the preoperative MVIC. Secondary endpoints included hip adductor and hip flexor MVIC, sensory levels in the femoral nerve distribution, hip range-of-motion, ambulatory ability, pain scores, and ropivacaine consumption. Results Quadriceps MVIC for patients receiving 0.1% ropivacaine (n = 26) declined by a mean (SE) of 64.1% (6.4) versus 68.0% (5.4) for patients receiving 0.4% ropivacaine (n = 24) between the preoperative period and the day after surgery (95% CI for group difference: -8.0-14.4%; P = 0.70). Similarly, the groups were found to be equivalent with respect to secondary endpoints. Conclusions For continuous posterior lumbar plexus blocks, local anesthetic concentration and volume do not influence nerve block characteristics, suggesting that local anesthetic dose (mass) is the primary determinant of perineural infusion effects.

Continuous femoral nerve blocks provide potent analgesia and other benefits after knee surgery. Perineural catheter placement techniques using ultrasound guidance and electrical stimulation (ES) have been described, but the optimal method remains undetermined. We tested the hypothesis that ultrasound guidance alone requires less time for femoral perineural catheter insertion and produces equivalent results compared with ES alone.Preoperatively, patients receiving a femoral perineural catheter for knee surgery were randomly assigned to either ultrasound guidance with a nonstimulating catheter or ES with a stimulating catheter. The primary outcome was the catheter placement procedure time (minutes) starting when the ultrasound transducer (ultrasound group) or catheter insertion needle (ES group) first touched the patient and ending when the catheter insertion needle was removed after catheter insertion.Perineural catheters placed with ultrasound guidance (n = 20) took a median (10th-90th percentiles) of 5.0 (3.9-10.0) minutes compared with 8.5 (4.8-30.0) minutes for ES (n = 20; P = .012). All ultrasound-guided catheters were placed according to the protocol (n = 20) versus 85% of ES-guided catheters (n = 20; P = .086). Patients in the ultrasound group had a median procedure-related discomfort score of 0.5 (0.0-3.1) compared with 2.5 (0.0-7.6) for the ES group (P = .015). There were no vascular punctures with ultrasound guidance versus 4 in the ES group (P = .039).Placement of femoral perineural catheters takes less time with ultrasound guidance compared with ES. In addition, ultrasound guidance produces less procedure-related pain and prevents inadvertent vascular puncture.

ANALGESIA for hip arthroplasty is traditionally provided by a multimodal regimen of oral and intravenous analgesics within the United States.1 However, postoperative opioid use is associated with undesirable side effects,2,3 and inadequate analgesia often results which interferes with sleep, general activity, and physical therapy.4 The latter is of particular importance because early mobilization is associated with decreased venous thromboembolism and shorter hospitalization as well as improved quality-of-life outcomes.5-7 An epidural infusion is thus often added to help mitigate these impediments to recovery.1 An alternative analgesic option is a continuous lumbar plexus block (cLPB) via the posterior approach.8 This technique involves the percutaneous insertion of a catheter directly into the ipsilateral psoas muscle in the lower lumbar region.9 The catheter is then infused with local anesthetic, resulting in potent, unilateral analgesia free of systemic side effects. Unlike femoral perineural infusion after total knee arthroplasty, cLPB for hip arthroplasty remains relatively uninvestigated—especially using the posterior approach. For example, data are unavailable from a randomized, masked, controlled trial even quantifying posterior cLPB analgesic potency and opioid sparing after hip arthroplasty. Similarly, any effect of a posterior cLPB on ambulation, hip flexion, sleep disturbances, or discharge readiness after hip arthroplasty remains unexamined and unknown. Previously published investigations involving hip arthroplasty provided posterior cLPB exclusively in hospitalized patients and are limited by one or more methodologic issues such as a retrospective study design; lack of randomization, adequately concealed treatment allocation (“blinding”), or placebo controls10; inadequate or missing sample-size estimates; or failure to specify primary endpoints a priori.11 An advantage of cLPB is that, unlike traditional intravenous opioid administration or epidural infusion, cLPB may be continued after discharge using a portable infusion pump.12 Consequently, ambulatory cLPB offers the potential of providing prolonged analgesia while simultaneously decreasing disability and hospitalization duration after hip arthroplasty and similar procedures. Use of ambulatory cLPB after hip arthroplasty has been reported just once, in a small series of subjects who were discharged home the day after surgery with their perineural infusions continuing for over 4 days.13 However, that investigation did not include a control group, and so the extent to which ambulatory cLPB influenced discharge readiness remains unknown. Therefore, the primary objective of this dual-center, randomized, triple-masked (patients, investigators, and statisticians), placebo-controlled study was to test the hypotheses that, compared with an overnight cLPB, a 4-day ambulatory cLPB increases ambulation distance and shortens the time until three specific, predefined readiness-for-discharge criteria are met after hip arthroplasty. The three discharge-related criteria were (1) adequate analgesia, (2) independence from intravenous opioids, and (3) sufficient ambulation. These criteria were chosen because failure to meet one or more of them accounts for the majority of hospitalization days in hip arthroplasty patients at our institutions. Secondary endpoints included maximum passive hip flexion, average and worst resting and dynamic pain scores, oral and intravenous opioid requirements, sleep disturbances, and patient satisfaction.

Resurfacing THA is an attractive treatment option for young patients because it saves the femoral head and is easily revisable. We assessed the clinical outcome of metal-on-metal hybrid total hip resurfacing for the treatment of 295 patients (350 hips) younger than 50 years of age (average, 41.2 years) and compared these results with those of patients 50 years or older (average, 57.4 years) at the time of surgery who were implanted with the same design. Seventy-five percent of the patients were male. The minimum followup was 2 years (mean 5.5 years; range 2-9 years). UCLA hip scores improved to 9.4 for pain; 9.6 for walking; 9.5 for function; and 7.6 for activity. We found no differences in survivorship between younger and older patients, and postoperative clinical scores related to the patients' physical health were comparable. There was no acetabular component loosening. Ten hips (2.8%) were revised for femoral aseptic loosening and one for femoral neck fracture. The 5-year survivorship of hips with good bone quality was 97.8%. There has been no femoral component loosening when the femoral stems were cemented irrespective of bone quality. Metal-on-metal resurfacing THA performs well at short to mid-term followup in young, active adults despite high activity levels.

Background: A theoretical advantage of resurfacing arthroplasty of the hip is that a failed femoral component can be safely and successfully revised to a total hip arthroplasty. To our knowledge, this advantage has not been demonstrated to date. Methods: Twenty-one metal-on-metal resurfacing arthroplasties in twenty patients with an average age of 50.2 years were converted to a conventional stemmed total hip arthroplasty because of femoral component failure. In eighteen hips, the acetabular component was retained, and in three hips both components were revised. The results in the resurfacing conversion group were compared with those in a group of fifty-eight patients who had undergone sixty-four primary total hip arthroplasties that had been performed during the same time-period by the same surgeon. Clinical evaluations (the Harris hip score, the University of California at Los Angeles pain, walking, and activity scores and the Short Form-12 score) and radiographic evaluations were performed. The average duration of follow-up was forty-six months for the conversion arthroplasty group and fifty-seven months for the primary conventional total hip arthroplasty group. Results: There was no significant difference between the conversion arthroplasty group and the conventional arthroplasty group with regard to operative time, blood loss, or complication rates. At the time of the most recent follow-up, with the numbers studied, there were no significant differences between the two groups with regard to the mean Harris hip score; the University of California at Los Angeles pain, walking, and activity score; or the SF-12 score. As assessed radiographically, the quality of component fixation and the alignment of the reconstruction were equivalent between the two groups. There had been no instances of aseptic loosening of the femoral or the acetabular component in either group, and there had been no dislocations after conversion of a resurfacing arthroplasty. Conclusions: Conversion of a hip resurfacing with a femoral-side failure to a total hip arthroplasty appears to be comparable with primary total hip arthroplasty in terms of surgical effort, safety, and early clinical outcomes. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

Copyright © 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Background: The authors conducted a randomized, controlled, parallel-arm, superiority study to test the hypothesis that a continuous adductor canal block decreases the time to attain four discharge criteria compared with a continuous femoral nerve block after tricompartment knee arthroplasty. Methods: Subjects undergoing tricompartment knee arthroplasty were randomized using computer-generated lists to either an adductor canal or femoral perineural catheter (3-day ropivacaine 0.2% infusion) in an unmasked manner. The primary outcome was the time to attain four criteria: (1) adequate analgesia; (2) intravenous opioids independence; (3) ability to stand, walk 3 m, return, and sit down; and (4) ambulate 30 m. Results: Subjects with an adductor canal catheter (n = 39) reached all four criteria in a median of 55 h (interquartile, 42 to 63 h) compared with 61 h (49 to 69 h) for those with a femoral catheter (n = 41; 95% CI, -13 to 1 h; P = 0.12). The percentage of subjects who reached the two mobilization criteria on postoperative days 1 and 2 were 72 and 95% for those with an adductor canal catheter (n = 39), but only 27 and 76% in subjects with a femoral catheter (n = 41; both P < 0.001). Differences in pain scores at rest and intravenous opioid requirements were minimal, but femoral infusion improved dynamic analgesia (P = 0.01 to 0.02). Conclusion: Compared with a continuous femoral nerve block, a continuous adductor canal block did not appreciably decrease the time to overall discharge readiness even though it did decrease the time until adequate mobilization, primarily because both groups experienced similar analgesia and intravenous opioid requirements that-in most cases-exceeded the time to mobilization.

Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105) and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis (RA) and osteoarthritis (OA) and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

The authors conducted a randomized, controlled, parallel-arm, superiority study to test the hypothesis that a continuous adductor canal block decreases the time to attain four discharge criteria compared with a continuous femoral nerve block after tricompartment knee arthroplasty.Subjects undergoing tricompartment knee arthroplasty were randomized using computer-generated lists to either an adductor canal or femoral perineural catheter (3-day ropivacaine 0.2% infusion) in an unmasked manner. The primary outcome was the time to attain four criteria: (1) adequate analgesia; (2) intravenous opioids independence; (3) ability to stand, walk 3 m, return, and sit down; and (4) ambulate 30 m.Subjects with an adductor canal catheter (n = 39) reached all four criteria in a median of 55 h (interquartile, 42 to 63 h) compared with 61 h (49 to 69 h) for those with a femoral catheter (n = 41; 95% CI, -13 to 1 h; P = 0.12). The percentage of subjects who reached the two mobilization criteria on postoperative days 1 and 2 were 72 and 95% for those with an adductor canal catheter (n = 39), but only 27 and 76% in subjects with a femoral catheter (n = 41; both P0.001). Differences in pain scores at rest and intravenous opioid requirements were minimal, but femoral infusion improved dynamic analgesia (P = 0.01 to 0.02).Compared with a continuous femoral nerve block, a continuous adductor canal block did not appreciably decrease the time to overall discharge readiness even though it did decrease the time until adequate mobilization, primarily because both groups experienced similar analgesia and intravenous opioid requirements that--in most cases--exceeded the time to mobilization.

Correspondence 6. Rennotte MT, Baele P, Aubert G, Rodenstein DO: Nasal con- tinuous positive airway pressure in the perioperative man- agement of patients with obstructive sleep apnea submitted to surgery. Chest 1995; 107:367–74 7. Wieczorek PM, Carli F: Obstructive sleep apnea uncovered after high spinal anesthesia: A case report. Can J Anaesth (Accepted for publication June 3, 2014.) Single-injection and Continuous Femoral Nerve Blocks Are Associated with Different Risks of Falling To the Editor: I read with interest the superb retrospective database study of Memtsoudis et al. titled, “Inpatients falls after total knee arthro- plasty: The role of anesthesia type and peripheral nerve blocks.” 1 Of more than 190,000 patients who underwent total knee arthroplasty (TKA), there was a fall incidence of 1.6%. Twelve percent of all patients had a “peripheral nerve block” (PNB), yet, as stated in the abstract, “Contrary to common concerns, no association was found between PNB and IF [inpatient falls].” However, within the limitations section, the authors explain that, “The database used contains limited clinical infor- mation and thus some important factors cannot be taken into account… With regard to information concerning PNB, spe- cific details on the exact type of block, if it was a continuous or single-shot application… are not readily discernible.” In other words, it remains unknown how many—or even if any—of the nearly 23,000 patients with “PNB” had a continuous PNB. This is a critical piece of (missing) information because the available data from previous studies that were able to differ- entiate between single-injection and continuous PNBs sug- gest a strong association of the latter with an increased risk of falls. In a retrospective database study, Wasserstein et al. found that—like Memtsoudis et al.—patients who underwent TKA with a single-injection femoral nerve block had the same risk of falling as patients without any type of PNB. 2 However, the presence of a continuous femoral nerve block increased the odds ratio of falling to 4.4 (p = 0.04). In a meta-analysis of three randomized, placebo-controlled trials involving femoral and posterior lumbar plexus catheters for TKA and total hip arthroplasty, respectively, Ilfeld et al. found that no subjects receiving perineural saline (n = 86) fell (0%) while there were seven falls (7%) in patients receiving perineural ropivacaine (n = 85; p = 0.01), strongly suggesting a causal relationship between the continuous blocks and falling. 3 Since there were no falls in the placebo group, an odds ratio cannot be calcu- lated; but, if even just a single fall occurred in this group, the odds ratio would be 5.5 (therefore, the actual odds ratio is at least 5.5, but possibly higher). Finally, an additional meta- analysis including 4 randomized, controlled trials and one retrospective cohort study, Johnson et al. calculated an odds ratio of 3.9 (p < 0.01) of falling for subjects with a continu- ous femoral or posterior lumbar plexus block of greater than 12 h (incidence = 2.2%) compared with subjects with either no block, a single-injection block, or a perineural infusion of less than 12 h (incidence = 0.5%). 4 To my knowledge, there are no data contradicting these findings when single-injection and continuous PNBs are differentiated. Why this apparent difference in the risk of falling exists between single-injection and continuous PNB remains unknown. Nevertheless, one may speculate that the reason single-injection blocks do not increase the risk of falling is simply because patients with flaccid quadriceps are not permitted out of bed—and do not attempt ambulation— without a good deal of caution and assistance. In contrast, patients with continuous PNB are not only permitted to get out of bed, but ambulate repeatedly in the early hours/ days following surgery. Given that falls with 4-day continu- ous PNB occur not only in the two days following surgery, but postoperative days 3 and 4 as well—after patients have successfully ambulated multiple times during physical ther- apy—there is a high probability that patients become more confident and do not continue to take the same precautions as during early ambulation attempts. 3 To support this sup- position, the majority of falls in patients with continuous PNB occur when patients are unaccompanied/unassisted and going to the restroom, often in the middle of the night. 5 Therefore, while I agree with the authors’ statement that their, “data should provide encouragement to not shy away from the use of PNB;” it should also not lull healthcare pro- viders into a false sense of security regarding the risks of con- tinuous PNB. Research involving the etiology of patient falls and their association with various regional analgesic inter- ventions must not decrease due to the important findings reported in the recent study by Memtsoudis et al. In addition, this letter should not be construed as criticizing the study by Memtsoudis et al.—the authors accurately and responsibly identified the limitation of their analysis within their discus- sion section—but, rather, a caution to readers of their article. Practitioners should at least be aware of the data specific to continuous PNB, as decreased cognizance or even denial of the issue may only increase the potential risk to our patients. Competing Interests The author declares no competing interests. Brian M. Ilfeld, M.D., M.S., University of California San Diego, San Diego, California. bilfeld@ucsd.edu References 1. Memtsoudis SG, Danninger T, Rasul R, Poeran J, Gerner P, Stundner O, Mariano ER, Mazumdar M: Inpatient falls after total knee arthroplasty: The role of anesthesia type and peripheral nerve blocks. A nesthesiology 2014; 120:551–63 2. Wasserstein D, Farlinger C, Brull R, Mahomed N, Gandhi R: Advanced age, obesity and continuous femoral nerve Anesthesiology 2014; 121:662-9 668 Correspondence

Identifying novel therapeutic targets for the treatment of disease is challenging. To this end, we developed a genome-wide approach of candidate gene prioritization. We independently collocated sets of genes that were implicated in rheumatoid arthritis (RA) pathogenicity through three genome-wide assays: (i) genome-wide association studies (GWAS), (ii) differentially expression in RA fibroblast-like synoviocytes (FLS), and (iii) differentially methylation in RA FLS. Integrated analysis of these complementary data sets identified a significant enrichment of multi-evidence genes (MEGs) within pathways relating to RA pathogenicity. One MEG is Engulfment and Cell Motility Protein-1 (ELMO1), a gene not previously considered as a therapeutic target in RA FLS. We demonstrated in RA FLS that ELMO1 is: (i) expressed, (ii) promotes cell migration and invasion, and (iii) regulates Rac1 activity. Thus, we created links between ELMO1 and RA pathogenicity, which in turn validates ELMO1 as a potential RA therapeutic target. This study illustrated the power of MEG-based approaches for therapeutic target identification.

BackgroundOsteochondral transfer procedures are increasingly used to resurface full-thickness articular cartilage defects. There has not been long-term assessment/description of autogenous donor and recipient sites.HypothesisThe healing process occurs at the donor/host cartilage and bone interfaces.Study DesignHistologic, biochemical, and biomechanical changes were assessed 6 months after an osteochondral transfer in a goat model.MethodsEight adult goats were studied. In the 6 osteochondral transfer goats, 2 autogenous plugs were transferred from the femoral trochlea to defects in the weightbearing portion of the medial femoral condyle. The goats were allowed free range for 6 months. Randomly assigned plugs were assessed.ResultsKnees of the sacrificed animals had preservation of the joint space with mild chondromalacic changes in both transfer and contralateral control groups. Histologically, no evidence of cartilage (host/donor) healing was seen. Subchondral bone of the plug was contiguous with the surrounding recipient bone. Cellular viability in the autogenous osteochondral plug was seen, and 35SO4 uptake of the articular cartilage was not statistically different from the contralateral control condyle. The indentation stiffness of the transfer plug (mosaicplasty) and the contralateral donor site were similar—much stiffer than normal cartilage including surrounding condylar cartilage. Large structural stiffness of transferred cores and donor sites appeared to be related to their thinner cartilage layer.ConclusionsAt 6-month follow-up, a cleft between host and transferred articular regions remained, with no integration between the two.Clinical RelevanceAutogenous transplantation of osteochondral plugs is possible with integration of subchondral bone and preservation of chondral viability.

Historically, fresh human osteochondral allografts have been stored in lactated Ringer's solution at 4 degrees C and then transplanted as quickly as possible, generally within 2 to 5 days, to ensure delivery of a high level of viable chondrocytes. Recently, allograft distribution companies have begun to provide fresh osteochondral allografts that are stored in a proprietary culture medium usually for at least 2 weeks before delivery to the surgeon for implantation. The effects of such storage on human cartilage have not been well-defined. In the current study the effects of storage in lactated Ringer's solution and in culture media were assessed. After 7 days of storage in lactated Ringer's solution, a significant decline in chondrocyte viability and metabolic activity was seen. Culture media provided significantly better preservation of the cartilage with viability and metabolic activity remaining essentially unchanged from baseline for as many as 14 days. The biochemical and biomechanical properties of the extracellular matrix remained stable with storage in both solutions with time. These data suggest that osteochondral allografts stored under traditional conditions in lactated Ringer's solution should continue to be implanted as quickly as possible and certainly within 7 days of donor death. If kept in culture media, the storage duration may be extended to approximately 2 weeks.

Background: Fresh osteochondral allograft transplantation is a well-established technique for the treatment of cartilage defects of the knee. It is believed that the basic paradigm of the technique is that the transplantation of viable chondrocytes maintains the articular cartilage matrix over time. Allograft tissue is typically transplanted up to forty-two days after the death of the donor, but it is unknown how the conditions and duration of storage affect the properties of fresh human osteochondral allografts. This study examined the quality of human allograft cartilage as a function of storage for a duration of one, seven, fourteen, and twenty-eight days. We hypothesized that chondrocyte viability, chondrocyte metabolic activity, and the biochemical and biomechanical properties of articular cartilage would remain unchanged after storage for twenty-eight days. Methods: Sixty osteochondral plugs were harvested from ten fresh human femoral condyles within forty-eight hours after the death of the donor and were stored in culture medium at 4°C. At one, seven, fourteen, and twenty-eight days after harvest, the osteochondral plugs were analyzed for (1) viability and viable cell density by confocal microscopy, (2) proteoglycan synthesis by quantification of 35SO4 incorporation, (3) glycosaminoglycan content, (4) indentation stiffness, (5) compressive modulus and hydraulic permeability by static and dynamic compression testing, and (6) tensile modulus by equilibrium tensile testing. Results: Chondrocyte viability and viable cell density remained unchanged after storage for seven and fourteen days (p > 0.7) and then declined at twenty-eight days (p 0.1) and then declined at fourteen days (p 0.8), indentation stiffness (p > 0.4), compressive modulus (p > 0.05), permeability (p > 0.3), or equilibrium tensile modulus after storage for twenty-eight days (p > 0.9). Conclusions: These data demonstrate that fresh human osteochondral allograft tissue stored for more than fourteen days undergoes significant decreases in chondrocyte viability, viable cell density, and metabolic activity, with preservation of glycosaminoglycan content and biomechanical properties. The cartilage matrix is preserved during storage for twenty-eight days, but the chondrocytes necessary to maintain the matrix after transplantation decreased over that time-period. Clinical Relevance: Fresh osteochondral allografting is well established and increasingly used, but little information is available about the changes in the tissue that occur during storage over a period of time. Surgeons who perform fresh osteochondral allograft transplantation should understand the consequences of prolonged storage on the quality of the graft.

© 2015 American Society of Regional Anesthesia and Pain Medicine. Background We tested the hypothesis that, following unicompartment knee arthroplasty, a continuous adductor canal block decreases the time to reach 4 discharge criteria compared with a continuous femoral nerve block. Methods Subjects were randomized to either an adductor canal or femoral perineural catheter (2-day ropivacaine 0.2% infusion) in an unmasked fashion. The primary outcome was the time to attain 4 discharge criteria: (1) adequate analgesia; (2) intravenous opioid independence; (3) ability to independently stand, walk 3 m, return, and sit down; and (4) ambulate 30 m. Results Subjects with an adductor canal catheter (n = 15) reached all 4 criteria in a median of 35 hours (interquartile range, 24-43 hours), compared with 40 hours (interquartile range, 27-69 hours) for those with a femoral catheter (n = 15; Wilcoxon rank sum test: P = 0.46; log-rank test: P = 0.16). However, the percentages of subjects (adductor canal: femoral) who reached the 2 mobilization criteria were 27%:0% on postoperative day (POD) 0, 93%:53% on POD 1, and 100%:73% on POD 2. Of adductor canal subjects, 100% were discharge ready by POD 2, compared with only 73% of femoral subjects (P < 0.001). Conclusions Compared with a continuous femoral nerve block, a continuous adductor canal block did not appreciably decrease the median number of hours to overall discharge readiness, yet did decrease the number of discrete days until discharge readiness. These results are applicable to only unicompartment knee arthroplasty and must be considered preliminary because of the limited sample size of this pilot study.

When approaching patients with a painful first MTP joint that has failed conservative therapy and first-line surgical treatments (cheilectomy or minor bunion procedures), the surgeon should stratify these patients based upon diagnosis, age, and activity level (Fig. 13). For the young, active patient, an arthrodesis is the gold standard, and the primary predictors of clinical and radiographic success are proper fusion angle alignment and maintenance or restoration of length. The method of fusion site preparation and the choice of fixation have not been found to be significant factors in achieving union, but based on the biomechanical data, we prefer the cup-and-cone method. Young, active patients with hallux rigidus also may be considered candidates for the investigational biologic interpositional arthroplasty procedures. Minimizing the bony resection and interposing soft tissue into the first MTP joint may provide symptomatic relief and maintain or restore motion and strength. Most importantly, this procedure does not seem to burn any bridges. If it fails, these patients can then be revised to an arthrodesis. In the elderly, inactive patient, arthrodesis is a safe and reliable treatment option. The Keller arthroplasty may be preferable, however, because it provides [figure: see text] excellent early symptomatic relief and has a less debilitating postoperative rehabilitation program. After Keller arthroplasty, patients may begin protected weight bearing immediately and after wound healing, may be advanced to weight bearing as tolerated. Whereas after fusion, most authors agree that patients should be nonweight bearing for 4-6 weeks or until there is some evidence of early radiographic union. In an older patient with inadequate upper extremity strength to manage crutches or a front-wheel walker, a first MTP fusion may result in prolonged confinement to a wheelchair. If the patient elects to undergo the Keller procedure, these patients should be counseled preoperatively about the potential complications of transfer metatarsalgia, cock-up deformity of the hallux, and weakness in the push-off phase of gait. The patients between these two extremes fall into a treatment gray zone. The arthrodesis should again be considered the gold standard because it is reliable and durable with time and activity. However, biologic or prosthetic interpositional arthroplasty are exciting investigational treatment options for these patients. If a prosthetic implant is to be used, the double-stemmed, hinged silastic implant with protective titanium grommets, or a metallic hemi-arthroplasty prosthesis, appear to be the two best choices of implant. With the continuous advances in material engineering and tissue engineering, prosthetic and biologic interpositional arthroplasties hold the greatest promise for the painful first MTP joint in the future. These treatment modalities allow restoration of alignment and maintenance of motion, length, and strength, which are fundamental in attaining a good clinical result. When the optimal material is developed (whether it is prosthetic, biologic, or a combination of both), these treatment advantages will be realized without the attendant complications associated with the use of our current implants.

Purpose: The objective of this study was to assess the short-term changes that occur after an osteochondral autograft plug transfer from the femoral trochlea to the medial femoral condyle in a goat model. Type of Study: Articular cartilage repair animal study. Methods: Six adult male goats were used in this study. Two 4.5-mm osteochondral plugs were transferred from the superolateral femoral trochlea to 2 recipient sites in the central portion of the medial femoral condyle for a survival period of 12 weeks. Postmortem, the global effects of the procedure were assessed by gross morphologic inspection and by analyzing the synovial DNA for inflammatory response. The recipient sites were also evaluated histologically and biomechanically. Metabolic activity was determined by 35 SO 4 uptake, and viability was assessed using a live/dead stain and by confocal laser microscopy. Results: There was no evidence of significant gross morphologic or histologic changes in the operative knee as a result of the osteochondral donor or recipient sites. The patella, tibial plateau, and medial meniscus did not show any increased degenerative changes as a result of articulating against the donor or recipient sites of the osteochondral autografts. Analysis of synovial DNA revealed no inflammatory response. Biomechanically, 6- to 7-fold greater stiffness was noted in the cartilage of the transferred plugs compared with the control medial femoral condyle. Furthermore, on histologic examination, the healing subchondral bone interface at the recipient site had increased density. Glycosaminoglycan synthesis as determined by 35 SO 4 uptake was upregulated in the transplanted cartilage plug relative to the contralateral control, showing a repair response at the site of implantation. And finally, confocal microscopy showed 95% viability of the transferred plugs in the medial femoral condyle region. Conclusions: Our findings demonstrate the ability to successfully transfer an osteochondral autograft plug with maintenance of chondrocyte cellular viability. The transferred cartilage is stiffer than the control medial femoral condyle cartilage, and there is concern regarding the increased trabecular mass in the healing subchondral plate, but these do not result in increased degenerative changes of the opposing articular surfaces in the short term. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 17, No 8 (October), 2001: pp 856–863

Serum cobalt (Co) and chromium (Cr) levels are commonly used to screen for excessive wear of metal-on-metal hip replacements. However, it is unknown how rapidly these should decline after revision. 25 patients with average Co and Cr ion levels of 56.3 μg/L and 20.5 μg/L were followed with serial ion level testing post-revision. Over the first 6 weeks post-revision, the rate of decline for Co and Cr was approximately 2% per day and this slowed to approximately 1% decline per day over the ensuing 6 weeks. This translated to a decline of approximately 80% from the starting value after 6 weeks and a decline of approximately 90% after 12 weeks post-revision. The rate of decline for both Co and Cr was significantly faster during the first 6 weeks (P0.001). In patients with ultra-high Cr levels20 μg/L, the rate of Cr decline is less predictable and may be protracted leading to persistent elevation above 5 μg/L for one year or more post-revision in some cases.

Class I phosphoinositide 3 kinase (PI3K) δ is a promising therapeutic target for rheumatoid arthritis (RA) because of its contribution to leukocyte biology. However, its contribution in fibroblasts has not been studied as a mechanism that contributes to efficacy. We investigated the expression and function of PI3Kδ in synovium and cultured fibroblast-like synoviocytes (FLS). Immunohistochemistry demonstrated that PI3Kδ is highly expressed in RA synovium, especially in the synovial lining. Using quantitative PCR and Western blot analysis, we found that PI3Kδ mRNA and protein expression is higher in RA than in osteoarthritis (OA) synovium. PI3Kδ was also expressed in cultured FLS, along with PI3Kα and PI3Kβ, whereas PI3Kγ was not detectable. PI3Kδ mRNA expression was selectively induced by inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) but not by growth factors platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ). The use of inhibitors that block individual PI3K isoforms, including the novel selective PI3Kδ inhibitor INK007, showed that PI3Kδ is required for PDGF- and TNF-induced Akt activation. PI3Kδ inhibition also diminished PDGF-mediated synoviocyte growth and sensitized cells to H 2 O 2 -induced apoptosis. These data are the first documentation of increased PI3Kδ expression in both RA synovium and cultured synoviocytes. Furthermore, these are the first data demonstrating that PI3Kδ is a major regulator of PDGF-mediated fibroblast growth and survival via Akt. Thus, targeting PI3Kδ in RA could modulate synoviocyte function via anti-inflammatory and disease-altering mechanisms.

A continuous femoral nerve block (cFNB) involves the percutaneous insertion of a catheter adjacent to the femoral nerve, followed by a local anesthetic infusion, improving analgesia following total knee arthroplasty (TKA). Portable infusion pumps allow infusion continuation following hospital discharge, raising the possibility of decreasing hospitalization duration. We therefore used a multicenter, randomized, triple-masked, placebo-controlled study design to test the primary hypothesis that a four-day ambulatory cFNB decreases the time until each of three predefined readiness-for-discharge criteria (adequate analgesia, independence from intravenous opioids, and ambulation ≥ 30 meters) are met following TKA compared with an overnight inpatient-only cFNB. Preoperatively, all patients received a cFNB with perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomized to either continue perineural ropivacaine (n=39) or switch to normal saline (n=38). Patients were discharged with their cFNB and portable infusion pump as early as postoperative day three. Patients given four days of perineural ropivacaine attained all three criteria in a median (25th–75th percentiles) of 47 (29–69) hours, compared with 62 (45–79) hours for those of the control group (Estimated ratio=0.80, 95% confidence interval: 0.66–1.00; p=0.028). Compared with controls, patients randomized to ropivacaine met the discharge criterion for analgesia in 20 (0–38) vs. 38 (15–64) hours (p=0.009), and intravenous opioid independence in 21 (0–37) vs. 33 (11–50) hours (p=0.061). We conclude that a four-day ambulatory cFNB decreases the time to reach three important discharge criteria by an estimated 20% following TKA compared with an overnight cFNB, primarily by improving analgesia.

The main determinant of continuous peripheral nerve block effects--local anesthetic concentration and volume or simply total drug dose--remains unknown.We compared two different concentrations and basal rates of ropivacaine--but at equivalent total doses--for continuous posterior lumbar plexus blocks after hip arthroplasty. Preoperatively, a psoas compartment perineural catheter was inserted. Postoperatively, patients were randomly assigned to receive perineural ropivacaine of either 0.1% (basal 12 ml/h, bolus 4 ml) or 0.4% (basal 3 ml/h, bolus 1 ml) for at least 48 h. Therefore, both groups received 12 mg of ropivacaine each hour with a possible addition of 4 mg every 30 min via a patient-controlled bolus dose. The primary endpoint was the difference in maximum voluntary isometric contraction (MVIC) of the ipsilateral quadriceps the morning after surgery, compared with the preoperative MVIC, expressed as a percentage of the preoperative MVIC. Secondary endpoints included hip adductor and hip flexor MVIC, sensory levels in the femoral nerve distribution, hip range-of-motion, ambulatory ability, pain scores, and ropivacaine consumption.Quadriceps MVIC for patients receiving 0.1% ropivacaine (n = 26) declined by a mean (SE) of 64.1% (6.4) versus 68.0% (5.4) for patients receiving 0.4% ropivacaine (n = 24) between the preoperative period and the day after surgery (95% CI for group difference: -8.0-14.4%; P = 0.70). Similarly, the groups were found to be equivalent with respect to secondary endpoints.For continuous posterior lumbar plexus blocks, local anesthetic concentration and volume do not influence nerve block characteristics, suggesting that local anesthetic dose (mass) is the primary determinant of perineural infusion effects.

The purpose of this randomized, single-blind clinical trial was to compare a rotating platform (RP) total knee arthroplasty to a fixed-bearing (FB) total knee arthroplasty. Ninety-five knees in 69 patients were implanted by 2 surgeons. There were no significant differences in the preoperative demographics. At a minimum of 2-year follow-up, clinical outcomes and complication rates were similar, with the exception that the RP group had significantly better stair-climbing scores (P = .04). Postoperative range of motion was equally good in both groups (FB knees, 1°-125°; RP knees, 1-126°). There were no bearing dislocations in the RP group. In conclusion, this RP design performs at least as well as the FB version, and the RP patients reported better stair-climbing ability. Enthusiasm for this finding should be tempered by the relatively small sample size.

With this technique, guide-pin placement and subsequent femoral head preparation can be performed accurately and efficiently without the need for additional instruments, navigation, or imaging.

We previously reported that extending an overnight continuous posterior lumbar plexus nerve block to 4 days after hip arthroplasty provides clear benefits during the perineural infusion in the immediate postoperative period. However, it remains unknown whether the extended infusion improves subsequent health-related quality of life.Patients undergoing hip arthroplasty received a posterior lumbar plexus perineural infusion of ropivacaine 0.2% from surgery until the following morning, at which time patients were randomized to continue either perineural ropivacaine (n = 24) or normal saline (n = 23) in a double-masked fashion. Patients were discharged with their catheter and a portable infusion pump, and catheters were removed on postoperative Day 4. Health-related quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index preoperatively and then at 7 days and 1, 2, 3, 6, and 12 mo after surgery. The WOMAC evaluates three dimensions of health-related quality of life, such as pain, stiffness, and physical functional disability (global score of 0-96, lower scores indicate lower levels of symptoms or physical disability). For inclusion in the primary analysis, we required a minimum of three of the six timepoints, including Day 7 and at least two of Months 3, 6, and 12.The two treatment groups had similar global WOMAC scores for the mean area under the curve calculations (point estimate for the difference in mean area under the curve for the two groups [extended infusion group-overnight infusion group] = 0.8, 95% confidence interval: -5.3 to + 6.8 [-5.5% to + 7.1%]; P = 0.80) and at all individual timepoints (P0.05).This investigation found no evidence that extending an overnight continuous posterior lumbar plexus nerve block to 4 days improves (or worsens) subsequent health-related quality of life between 7 days and 12 mo after hip arthroplasty.

The recent, encouraging outcome literature on hip resurfacing arthroplasty (HRA) has not sufficiently examined the potential occurrence of postoperative femoroacetabular impingement (PFAI) and sequelae. The current study asks the questions, "Does femoroacetabular impingement occur after hip resurfacing arthroplasty (HRA) and, if so, what are the clinical outcomes?"Sixty-nine consecutive hips in 57 patients with a minimum of 2 years clinical and radiographic follow-up were evaluated. Both acetabular and femoral component positions and postsurgical changes in the femoral neck and acetabulum were recorded.Fourteen hips in 13 patients (20%) developed a small scalloped, corticated erosion in the posterior neck, just distal to the femoral component and adjacent to the acetabular component rim. These erosions were between 5 and 10 mm in depth and became apparent at an average of 15 months (range, 6 to 24 months) following surgery. After 2 years, they showed no further progression. The location and shape of the erosions indicate PFAI as the etiology. One hip also demonstrated similar changes in the anterior neck. The Harris Hip Score and UCLA (University of California at Los Angeles) Activity Scores were higher in patients with such erosions (97.5 and 9.2, respectively), compared to those patients without (93.5 and 8.4, respectively). Additionally, patients with erosions reported slightly better pain relief on average than patients with no radiographic evidence of impingement. No significant differences in range of motion or component position were found between the two groups.Small, corticated, non-progressive erosions can occur from femoroacetabular impingement following HRA. The erosions were more commonly posterior in this series, and they tended to occur in active patients. There is no adverse effect on clinical outcomes, and more specifically, there is no association of PFAI with pain.

The authors tested the hypotheses that after hip arthroplasty, ambulation distance is increased and the time required to reach three specific readiness-for-discharge criteria is shorter with a 4-day ambulatory continuous lumbar plexus block (cLPB) than with an overnight cLPB.A cLPB consisting of 0.2% ropivacaine was provided from surgery until the following morning. Patients were then randomly assigned either to continue ropivacaine or to be switched to normal saline. Primary endpoints included (1) time to attain three discharge criteria (adequate analgesia, independence from intravenous analgesics, and ambulationor = 30 m) and (2) ambulatory distance in 6 min the afternoon after surgery. Patients were discharged with their cLPB and a portable infusion pump, and catheters were removed on the fourth postoperative day.Patients given 4 days of perineural ropivacaine (n = 24) attained all three discharge criteria in a median (25th-75th percentiles) of 29 (24-45) h, compared with 51 (42-73) h for those of the control group (n = 23; estimated ratio = 0.62; 95% confidence interval, 0.45-0.92; P = 0.011). Patients assigned to receive ropivacaine ambulated a median of 34 (9-55) m the afternoon after surgery, compared with 20 (6-46) m for those receiving normal saline (estimated ratio = 1.3; 95% confidence interval, 0.6-3.0; P = 0.42). Three falls occurred in subjects receiving ropivacaine (13%), versus none in subjects receiving normal saline.Compared with an overnight cLPB, a 4-day ambulatory cLPB decreases the time to reach three predefined discharge criteria by an estimated 38% after hip arthroplasty. However, the extended infusion did not increase ambulation distance to a statistically significant degree.

We previously reported wear data at a minimum of two years following thirty-four total hip replacements with a Marathon cross-linked polyethylene liner and twenty-four replacements with a conventional (gamma-sterilized-in-air) Enduron polyethylene liner. In this current study, with sequential five-year radiographs, wear rates were determined with use of linear regression analysis. The Marathon polyethylene had average wear rates of 15.4 mm3/yr and 8.0 mm3/million cycles. The Enduron polyethylene had average wear rates of 55.5 mm3/yr and 29.9 mm3/million cycles. The adjusted volumetric wear rate of the Marathon polyethylene was 73% lower than that of the Enduron polyethylene (p = 0.001). Osteolysis developed in eight of the twenty-four hips with an Enduron liner but was not apparent in any hip with a Marathon liner. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.