Association Between Initial Prescription Size and Likelihood of Opioid Refill After Total Knee and Hip Arthroplasty.

BACKGROUND: The present study was designed to test the hypothesis that there was no association between initial opioid prescription size and the likelihood of refill after elective primary total knee (TKA) and hip arthroplasty (THA). METHODS: We retrospectively analyzed large national datasets of commercial and Medicare insurance claims to identify a weighted cohort of 120,889 primary total joint arthroplasties (76,900 TKA and 43,989 THA) comprised of opioid-naive patients aged 18 to 75 years who had surgery between January 2015 and November 2019. The primary outcome was refill of any prescription opioid medication within 30 days after discharge, and the primary predictor variable was the total amount of opioid filled in the initial discharge prescription measured in oral morphine equivalents (OMEs). Logistic regressions were used to estimate the likelihood of refill, given a particular prescription size while adjusting for multiple patient factors, including age, sex, comorbidities, and year of surgery. RESULTS: The 30-day refill rate was 59.6% following TKA and 26.1% for THA. Adjusted odds of refill decreased by 2% for every 75 OME (10 tablets of 5 mg oxycodone) increase to the initial prescription size among the THA cohort (adjusted odds ratio [OR] = 0.98; 95% CI 0.97-0.99), and decreased by 3% for the TKA cohort (aOR = 0.97; 95% CI 0.97-0.98). CONCLUSION: These nationally representative data demonstrated that larger initial opioid prescription size was associated with small but clinically insignificant decreases in 30-day refill after total joint arthroplasty. This finding should allay concerns about efforts to decrease postsurgical opioid prescribing.

New persistent opioid use after surgery in patients with a history of remote opioid use.

BACKGROUND: Postoperative pain management is particularly challenging in patients using opioids preoperatively, but previous studies have not stratified patients not using opioids at the time of surgery according to history of opioid use. This study was designed to test the hypothesis that history of opioid use among patients not reporting opioid use at the time of surgery was independently associated with new persistent opioid use after surgery. METHODS: Using prospective perioperative data from the Analgesic Outcomes Study, we assessed outcomes of patients 18 years of age or older who underwent elective surgery between December 2015 and January 2019 and were not using opioids at the time of surgery. Patient self-reported outcome measures were collected on the day of surgery and at 2 weeks, 1 month, and 3 months postoperatively. The primary outcome was new persistent opioid use, defined as continued opioid use 3 months after surgery. The primary explanatory variable was history of opioid use, which was categorized as no history of opioid use, history of non-continuous opioid use, or history of continuous opioid use (defined as daily or almost every day for 3 months or longer). Other covariates included demographics, validated measures (pain, mood), surgery type and approach, comorbidities, and use of tobacco, alcohol, cannabis, and benzodiazepines. Backward stepwise logistic regression models were used to determine patient factors associated with new persistent opioid use and refill after surgery. RESULTS: A total of 1,249 patients not taking opioids preoperatively were included in the study cohort for new persistent opioid use. A total of 54 (4.3%) patients had continued use 3 months after surgery. New persistent opioid use after surgery was independently associated with non-continuous opioid use history (adjusted odds ratio 2.9, [95% confidence interval, 1.21 to 6.94]), continuous opioid use history (adjusted odds ratio 5.0, [95% confidence interval, 1.48 to 16.76]), and moderate to high alcohol use (adjusted odds ratio 2.5, [95% confidence interval, 1.24 to 4.93]). Similarly, opioid prescription refill at 1 month after surgery was independently associated with history of non-continuous opioid use (adjusted odds ratio 1.6, [95% confidence interval, 1.12 to 2.24]), history of continuous opioid use (adjusted odds ratio 2.2, [95% confidence interval, 1.15 to 4.06]), and moderate to high alcohol use (adjusted odds ratio 1.7, [95% confidence interval, 1.18 to 2.48]). CONCLUSION: Among patients not using opioids preoperatively, a history of opioid use was independently associated with new persistent opioid use after surgery, especially those with a history of continuous opioid use.

Reasons for Preoperative Opioid Use Are Associated with Persistent Use following Surgery Among Patients Undergoing Total Knee and Hip Arthroplasty.

OBJECTIVE: Most studies on preoperative opioid use only describe whether or not patients use opioids without characterizing reasons for use. Knowing why patients use opioids can help inform perioperative opioid management. The objective of this study was to explore pain specific reasons for preoperative opioid use prior to total hip and knee arthroplasty (THA and TKA) and their association with persistent use. METHODS: This is a prospective study of 197 patients undergoing THA (n = 99) or TKA (n = 98) enrolled in the Analgesic Outcomes Study between December 2015 and November 2018. All participants reported preoperative opioid use. RESULTS: Reasons for preoperative opioid use were categorized as surgical site pain only (81 [41.1%]); pain in other body areas only (22 [11.2%]); and combined pain (94 [47.7%]). Compared to patients taking opioids for surgical site pain, those with combined reasons for use had 1.24 (P = .40) and 2.28 (P = .16) greater odds of persistent use at 3 and 6 months postoperatively, adjusting for relevant covariates. CONCLUSIONS: This study provides novel insights into the heterogeneity of reasons for presurgical opioid use in patients undergoing a THA or TKA. One key take away is that not all preoperative opioid use is the same and many patients are taking opioids preoperatively for more than just pain at the surgical site. Combined reasons for use was associated with long-term use, suggesting nonsurgical pain, in part, drives persistent opioid use after surgery. Future directions in perioperative care should focus on pain and non-pain reasons for presurgical opioid use to create tailored postoperative opioid weaning plans.

Patient Factors Associated With Opioid Consumption in the Month Following Major Surgery.

OBJECTIVE: The aim of this study was to determine preoperative patient characteristics associated with postoperative outpatient opioid use and assess the frequency of postoperative opioid overprescribing. SUMMARY BACKGROUND DATA: Although characteristics associated with inpatient opioid use have been described, data regarding patient factors associated with opioid use after discharge are lacking. This hampers the development of individualized approaches to postoperative prescribing. METHODS: We included opioid-naïve patients undergoing hysterectomy, thoracic surgery, and total knee and hip arthroplasty in a single-center prospective observational cohort study. Preoperative phenotyping included self-report measures to assess pain severity, fibromyalgia survey criteria score, pain catastrophizing, depression, anxiety, functional status, fatigue, and sleep disturbance. Our primary outcome measure was self-reported total opioid use in oral morphine equivalents. We constructed multivariable linear-regression models predicting opioids consumed in the first month following surgery. RESULTS: We enrolled 1181 patients; 1001 had complete primary outcome data and 913 had complete phenotype data. Younger age, non-white race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were significantly associated with increased opioid consumption. Median total oral morphine equivalents prescribed was 600 mg (equivalent to one hundred twenty 5-mg hydrocodone pills), whereas median opioid consumption was 188 mg (38 pills). CONCLUSIONS: In this prospective cohort of opioid-naïve patients undergoing major surgery, we found a number of characteristics associated with greater opioid use in the first month after surgery. Future studies should address the use of non-opioid medications and behavioral therapies in the perioperative period for these higher risk patients.

Post-operative urinary retention after lower extremity arthroplasty and the peri-operative role of selective alpha-1 adrenergic blocking agents in adult male patients: a propensity-matched retrospective cohort study.

PURPOSE: The purpose of this study was to determine whether male patients taking pre-operative selective alpha-1 adrenergic blocking agents have a lower likelihood of developing post-operative urinary retention (POUR) and a shorter length of hospitalization following lower extremity arthroplasty. METHODS: A retrospective cohort study was conducted of patients who underwent primary or revision total hip or knee arthroplasty, or unicompartmental knee arthroplasty at an academic institution from January 2002 to May 2014. A cohort of male patients aged 35 and older who were taking a selective alpha-1 blocker prior to surgery (N = 229) were compared with a control group (N = 330) not taking one of these medications. Propensity score-matched logistic regression was performed to isolate the effect of taking a selective alpha-1 blocker on POUR. RESULTS: When evaluating for the outcome of POUR while controlling for age, hypertension, benign prostatic hyperplasia, urinary tract infections, type of anaesthesia, and procedure, those patients taking an alpha-1 blocker had a 12.1% decreased relative risk (95% CI 3.4 to 20.8%; p = 0.007) of developing POUR compared with patients not taking these medications. Mean length of stay was 3.8 days (95% CI 3.6 to 4.1) in the cohort taking selective alpha-1 blockers compared with 4.7 days (95% CI 4.4 to 4.9) for the control cohort. CONCLUSIONS: After controlling for known risk factors for the development of POUR, the use of selective alpha-1 blockers pre-operatively reduces the risk of developing urinary retention after lower extremity arthroplasty and is associated with a 1-day decreased length of stay.

Angiogenic and Arthritogenic Properties of the Soluble Form of CD13.

Aminopeptidase N/CD13 is expressed by fibroblast-like synoviocytes (FLS) and monocytes (MNs) in inflamed human synovial tissue (ST). This study examined the role of soluble CD13 (sCD13) in angiogenesis, MN migration, phosphorylation of signaling molecules, and induction of arthritis. The contribution of sCD13 was examined in angiogenesis and MN migration using sCD13 and CD13-depleted rheumatoid arthritis (RA) synovial fluids (SFs). An enzymatically inactive mutant CD13 and intact wild-type (WT) CD13 were used to determine whether its enzymatic activity contributes to the arthritis-related functions. CD13-induced phosphorylation of signaling molecules was determined by Western blotting. The effect of sCD13 on cytokine secretion from RA ST and RA FLS was evaluated. sCD13 was injected into C57BL/6 mouse knees to assess its arthritogenicity. sCD13 induced angiogenesis and was a potent chemoattractant for MNs and U937 cells. Inhibitors of Erk1/2, Src, NF-κB, Jnk, and pertussis toxin, a G protein-coupled receptor inhibitor, decreased sCD13-stimulated chemotaxis. CD13-depleted RA SF induced significantly less MN migration than sham-depleted SF, and addition of mutant or WT CD13 to CD13-depleted RA SF equally restored MN migration. sCD13 and recombinant WT or mutant CD13 had similar effects on signaling molecule phosphorylation, indicating that the enzymatic activity of CD13 had no role in these functions. CD13 increased the expression of proinflammatory cytokines by RA FLS, and a CD13 neutralizing Ab inhibited cytokine secretion from RA ST organ culture. Mouse knee joints injected with CD13 exhibited increased circumference and proinflammatory mediator expression. These data support the concept that sCD13 plays a pivotal role in RA and acute inflammatory arthritis.

The AAHKS Clinical Research Award: Prophylactic Tamsulosin Does Not Reduce the Risk of Urinary Retention Following Lower Extremity Arthroplasty: A Double-Blinded Randomized Controlled Trial.

BACKGROUND: Postoperative urinary retention (POUR) is common. Selective alpha-1 adrenergic antagonists, such as tamsulosin, are effective for treating urinary retention. The purpose of this study is to determine whether perioperative prophylactic tamsulosin reduces the incidence of POUR following total hip and knee arthroplasty. METHODS: Male patients 35 years of age and older undergoing primary total hip or knee arthroplasty at a single center from 2015 to 2018 were eligible for inclusion. Patients were randomized to receive tamsulosin 0.4 mg or placebo daily for 5 days preoperatively, the morning of surgery, and the first postoperative day. The incidence of POUR was determined during the postoperative hospitalization. RESULTS: A total of 176 patients were enrolled in the study. Two patients were withdrawn prior to randomization. The remaining 174 were randomized to tamsulosin (n = 87) or placebo (n = 87). After an additional 43 patients were withdrawn prior to surgery, 131 patients completed the study (tamsulosin, n = 64; placebo, n = 67). A total of 42 patients (32.1%) developed POUR, with 18 cases (28.1%) in the tamsulosin group and 24 cases (35.8%) in the placebo group (P = .345), resulting in an odds ratio of 0.701 and a risk difference of 7.69%. CONCLUSION: Prophylactic tamsulosin did not reduce the incidence of POUR after hip and knee arthroplasty compared to placebo. The odds ratio indicates an approximately 30% decreased odds of developing POUR in the tamsulosin group, albeit not statistically significant. Tamsulosin does not appear to be effective as a prophylactic measure for reducing POUR in male hip and knee arthroplasty patients.

Association Between the 2011 Fibromyalgia Survey Criteria and Multisite Pain Sensitivity in Knee Osteoarthritis.

OBJECTIVES: The present study evaluated the relationship between the 2011 American College of Rheumatology fibromyalgia (FM) survey criteria and quantitative sensory testing (QST). MATERIALS AND METHODS: Patients with knee osteoarthritis scheduled to undergo knee arthroplasty completed the FM survey criteria and self-report measures assessing clinical symptoms. Patients also underwent a battery of QST procedures at the surgical knee and remote body sites, including pressure algometry, conditioned pain modulation, and temporal summation. All assessments were completed before surgery. FM survey criteria were used to calculate a continuous FM score indicating FM severity. RESULTS: A total of 129 patients were analyzed. Of these, 52.7% were female, 93.8% were Caucasian, and 3.8% met the FM survey criteria for FM classification. Mean age for females (63.6 y) and males (64.7 y) was similar. Females and males differed significantly in nearly every outcome, including FM severity, clinical pain, anxiety, depression, and pressure pain sensitivity. In females, FM scores significantly correlated with pressure pain sensitivity, but not conditioned pain modulation or temporal summation, such that increased sensitivity was associated with greater FM severity at all body sites examined. In addition, as FM scores increased, the association between pain sensitivity at the surgical knee and pain sensitivity at remote body sites also increased. No relationship between FM score and QST was observed in males. DISCUSSION: We demonstrated an association between diffuse hyperalgesia as measured by QST and FM severity in females with knee osteoarthritis. These results suggest that the FM survey criteria may represent a marker of pain centralization in females with potential utility in clinical decision making.

Post-operative medical and surgical complications after primary total joint arthroplasty in solid organ transplant recipients: a case series.

PURPOSE: In a series of solid organ transplant (SOT) recipients who underwent a subsequent primary total joint arthroplasty (TJA) procedure, this study aimed to determine: (1) 90-day morbidity and mortality after primary total knee or hip arthroplasty (TKA and THA), (2) overall post-operative infection rates, and (3) how complication and infection rates compared across primary TJA procedure and type of transplant organ. METHODS: The University of Michigan Health System database was retrospectively searched using current procedural terminology codes for any primary TKA or THA performed at the institution in years 2000-2012 in a patient who previously received a successful SOT at any hospital. RESULTS: The search yielded 44 arthroplasties performed in 29 SOT recipients (average age 54.8 years, average follow-up about 30 months for both groups). No deaths were reported, but 13/27 (48.1%) THA patients and 2/6 (33.3%) TKA patients experienced a total of 29 complications within 90 days of surgery. One patient (3.7%) [1/27 patients, 1/37 joints] underwent revision hip arthroplasty to correct limb length. One THA patient and two TKA patients developed infection requiring revision surgery (3.7% and 33%, respectively). Type of transplant did not affect complication rates (P=0.65), and infection was more common after TKA (P=0.01). CONCLUSIONS: A series of SOT recipients demonstrated increased rates of infection and other complications following TJA. Surgical and medical teams should work closely to optimize this population for TJA surgery and minimize peri-operative complications. LEVEL OF EVIDENCE & STUDY DESIGN: Level IV, Prognostic Case-Series.

No Difference in Dislocation Seen in Anterior Vs Posterior Approach Total Hip Arthroplasty.

BACKGROUND: The direct anterior approach (DAA) for total hip arthroplasty (THA) has rapidly become popular, but there is little consensus regarding the risks and benefits of this approach in comparison with a modern posterior approach (PA). METHODS: A total of 2147 patients who underwent DAA THA were propensity score matched with patients undergoing PA THA on the basis of age, gender, body mass index, and American Society of Anesthesia classification using data from a state joint replacement registry. Mean age of the matched cohort was 64.8 years, mean body mass index was 29.1 kg/m(2), and 53% were female. Multilevel logistic regression models using generalized estimating equations to control for grouping at the hospital level were used to identify differences in various outcomes. RESULTS: There was no difference in the dislocation rate between patients undergoing DAA (0.84%) and PA (0.79%) THA. Trends indicating a slightly longer length of stay with the PA and a slightly greater risk of fracture, increased blood loss, and hematoma with the DAA are consistent with previous studies. CONCLUSION: On the basis of short-term outcome and complication data, neither approach has a compelling advantage over each other, including no difference in the dislocation risk.

Proportion of Obese Patients Presenting to Orthopedic Total Joint Arthroplasty Clinics.

The purpose of this study is to demonstrate that the percentage of obese individuals initially presenting to total joint arthroplasty clinics in a public, tertiary hospital is greater than the proportion of obese individuals in the general population. In a retrospective, comparative study of patients seen in total joint replacement clinics at a public, tertiary hospital with an ICD-9 diagnosis of hip or knee osteoarthritis and documented body mass index, the proportion of obese individuals was compared with recent obesity data for the general population from the Centers for Disease Control and Prevention. Patients who had previously undergone hip or knee replacement surgery were excluded. Comorbid conditions, functional comorbidity index (FCI) scores, and Charlson comorbidity index scores were compared between obese and nonobese cohorts. The study included 499 patients aged 20 to 92 years (mean, 64.3 years), 58.9% of whom were female. Fifty-five percent of patients were obese, a significantly greater percentage than in the national (34.9%; P<.0005; odds ratio [OR]=2.23), regional (29.5%; P<.0005; OR=2.85), and state (31.1%; P<.0005; OR=2.64) populations. Obese patients had significantly more comorbid conditions (P<.002) and higher functional comorbidity index scores (P<.0009). The number of comorbidities and having Medicare/Medicaid insurance were predictive of obesity. This study highlights that the majority of patients presenting to orthopedic total joint arthroplasty clinics are obese and that they come with significantly more comorbidities. The total joint surgeon has a unique opportunity to facilitate weight loss in the obese osteoarthritic patient prior to joint replacement.

Patients' perceptions of the costs of total hip and knee arthroplasty.

With medical economics in the national sociopolitical spotlight, we conducted a study to assess patients' understanding of the cost of 2 common orthopedic procedures: total hip and knee arthroplasty (THA, TKA). We surveyed 284 consecutive THA or TKA patients, at their first postoperative visit, regarding their understanding of reimbursement and cost. On average, patients estimated surgeon reimbursement at $12,014. They estimated that the hospital was reimbursed $28,392 for their perioperative care and that it cost the hospital $24,389 to provide it. The cost of the implant used was estimated at $6447. There is wide variation in patients' estimates and understanding of health care costs. However, patients substantially overestimate reimbursement to the surgeon both in isolation and as a proportion of the total cost of the surgical procedure.

Characteristics of fibromyalgia independently predict poorer long-term analgesic outcomes following total knee and hip arthroplasty.

OBJECTIVE: While psychosocial factors have been associated with poorer outcomes after knee and hip arthroplasty, we hypothesized that augmented pain perception, as occurs in conditions such as fibromyalgia, may account for decreased responsiveness to primary knee and hip arthroplasty. METHODS: A prospective, observational cohort study was conducted. Preoperative phenotyping was conducted using validated questionnaires to assess pain, function, depression, anxiety, and catastrophizing. Participants also completed the 2011 fibromyalgia survey questionnaire, which addresses the widespread body pain and comorbid symptoms associated with characteristics of fibromyalgia. RESULTS: Of the 665 participants, 464 were retained 6 months after surgery. Since individuals who met criteria for being classified as having fibromyalgia were expected to respond less favorably, all primary analyses excluded these individuals (6% of the cohort). In the multivariate linear regression model predicting change in knee/hip pain (primary outcome), a higher fibromyalgia survey score was independently predictive of less improvement in pain (estimate -0.25, SE 0.044; P < 0.00001). Lower baseline joint pain scores and knee (versus hip) arthroplasty were also predictive of less improvement (R(2) = 0.58). The same covariates were predictive in the multivariate logistic regression model for change in knee/hip pain, with a 17.8% increase in the odds of failure to meet the threshold of 50% improvement for every 1-point increase in fibromyalgia survey score (P = 0.00032). The fibromyalgia survey score was also independently predictive of change in overall pain and patient global impression of change. CONCLUSION: Our findings indicate that the fibromyalgia survey score is a robust predictor of poorer arthroplasty outcomes, even among individuals whose score falls well below the threshold for the categorical diagnosis of fibromyalgia.

Musculoskeletal care of the hemophiliac patient.

Hemophilia is caused by a deficiency of clotting factor VIII or IX and is inherited by a sex-linked recessive pattern. von Willebrand disease, a common, moderate bleeding disorder, is caused by a quantitative or qualitative protein deficiency of von Willebrand factor and is inherited in an autosomal dominant or recessive manner. The most important clinical strategy for the management of patients with hemophilia is the avoidance of recurrent hemarthrosis by continuous, intravenous hematologic prophylaxis. Early hemarthrosis should be aggressively managed with aspiration and clotting factor concentrate until the joint examination is normal. Starting prophylactic factor replacement in infancy may prevent chronic synovitis and arthropathy. The natural history of poorly controlled disease is polyarticular hemophilic arthropathy; functional prognosis is poor. Patients with chronic synovitis may be treated effectively with radiosynovectomy; those who develop joint surface erosions may require realignment osteotomies, joint arthroplasty, and treatment of pseudotumors. Reconstructive surgery for hemophilic arthropathy, especially in patients with factor inhibitor, requires careful hematologic management by an experienced, multidisciplinary team.

Total hip arthroplasty in adolescents with severe hip arthropathy and dysplasia associated with camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare disorder. Patients with this syndrome experience early symptomatic arthropathy of the hips. We report a case of adolescent siblings with bilateral arthropathy associated with CACP syndrome in which total hip arthroplasty was performed as treatment of severe associated disability. Postoperative Harris Hip Scores for patient 1 were 86 for the right at 18 months and 96 for the left at 12 months. Postoperative Harris Hip Score at 6 months for patient 2 was 53; however, he had good range of motion and lacked deformity. Based on our limited experience and the limited available clinical data, we feel that total hip arthroplasty is a reasonable treatment option for adolescents with debilitating hip arthropathy associated with CACP syndrome.

Total hip arthroplasty modular neck failure.

The use of modular components in total hip arthroplasty has increased in popularity. The advantages of modularity in hip arthroplasty include improved visualization during acetabular revision and restoration of proper hip biomechanics. Disadvantages include disassociation of components, failure at modular junctions, corrosion, and the generation of metal ions and debris. We present 2 cases that demonstrate the potential for modular neck fracture, requiring subsequent revision of well-fixed components.

Synovial inflammation in patients with osteonecrosis of the femoral head.

Much of the work aimed at elucidating the pathogenesis of osteonecrosis (ON) of the femoral head has focused on bone blood supply, with little attention to the surrounding synovial tissue (ST). We hypothesized that patients with ON exhibit synovial inflammation. Using immunohistological techniques, we found that a large population of patients with ON had synovial inflammation. Moreover, a population of ON patients had inflamed ST without having an inflammatory disease co-morbidity. The inflammatory infiltrate in these patients comprised primarily CD4(+) T cells and CD68(+) macrophages, the latter of which expressed increased levels of cellular adhesion molecules. Our results suggest the presence of a previously unrecognized population of ON patients without a diagnosed inflammatory co-morbidity and a highly inflammed synovium consisting primarily of a macrophage and CD4(+) T-cell infiltrate.

Selecting and starting an orthopaedic surgery practice.

Every new surgeon is faced with the same question as their residency or fellowship draws to a close: What is next? Few residents or fellows are as well prepared to answer that question as they could be. Most programs do not teach residents how to choose a practice type and location. After formal orthopaedic training, new surgeons must make decisions about their careers that can be nearly as complex and difficult as the decisions they make in the operating room. Career choices have both significant and long-term effects on the physician's financial situation, career satisfaction, and personal life. The physician should be aware of key non academic issues that arise when completing a residency program or just beginning the practice of orthopaedic surgery.

Molecular interactions between T cells and fibroblast-like synoviocytes: role of membrane tumor necrosis factor-alpha on cytokine-activated T cells.

The mechanism of fibroblast-like synoviocyte (FLS) transformation into an inflammatory phenotype in rheumatoid arthritis (RA) is not fully understood. FLS interactions with invading leukocytes, particularly T cells, are thought to be a critical component of this pathological process. Resting T cells and T cells activated through the T-cell receptor have previously been shown to induce inflammatory cytokine production by FLS. More recently, a distinct population of T cells has been identified in RA synovium that phenotypically resembles cytokine-activated T (Tck) cells. Using time lapse microscopy, the interactions of resting, superantigen-activated, and cytokine-activated T cells with FLS were visualized. Rapid and robust adhesion of Tck and superantigen-activated T cells to FLS was observed that resulted in flattening of the T cells and a crawling movement on the FLS surface. Tck also readily activated FLS to produce interleukin IL-6 and IL-8 in a cell contact-dependent manner that was enhanced by exogenous IL-17. Although LFA-1 and ICAM-1 co-localized at the Tck-FLS synapse, blocking the LFA-1/ICAM-1 interaction did not substantially inhibit Tck effector function. However, antibody blocking of membrane tumor necrosis factor (TNF)-alpha on the Tck surface did inhibit FLS cytokine production, thus illustrating a novel mechanism for involvement of TNF-alpha in cell-cell interactions in RA synovium and for the effectiveness of TNF-alpha blockade in the treatment of RA.