Digital musculoskeletal program is associated with decreased joint replacement rates.

OBJECTIVES: To compare 12-month total knee arthroplasty (TKA) and total hip arthroplasty (THA) rates for digital musculoskeletal (MSK) program members vs patients who received traditional care for knee or hip osteoarthritis (OA). STUDY DESIGN: Retrospective, longitudinal study with propensity score-matched comparison group that used commercial medical claims data representing more than 100 million commercially insured lives. METHODS: Study participants with hip OA (M16.x) or knee OA (M17.x) International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were identified in the medical claims database. Digital MSK program members were identified using record linkage tokens. The comparison group had hip- or knee-related physical therapy identified via ICD-10-CM and Current Procedural Terminology codes. Respectively in each knee and hip OA group, digital members were matched to control group patients with similar demographics, comorbidities, and baseline MSK-related medical care use. TKA and THA at 12 months post participation were compared. RESULTS: In the knee OA group, 739 of 56,634 control group patients were matched to 739 digital members. At 12 months, 3.79% of digital members and 14.21% of control group patients had TKA (difference, 10.42%; P < .001). In the hip OA group, 141 of 20,819 control group patients were matched to 141 digital members. At 12 months, 16.31% of digital members and 32.62% of control group patients had THA (difference, 16.31%; P = .001). CONCLUSIONS: These findings suggest that patients who participated in a digital MSK program to manage OA have lower rates of total joint arthroplasty in the 12 months after enrollment.

Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma.

PURPOSE: Current guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many of these patients develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment of these patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high (class 2). Prospective analysis of CM outcomes was performed to test the hypotheses that the 31-GEP provides prognostic value for patients with stage I-III CM, and that patients with stage I-IIA melanoma and class 2 31-GEP results have metastatic risk similar to patients for whom surveillance is recommended. MATERIALS AND METHODS: Two multicenter registry studies, INTEGRATE (ClinicalTrials.gov identifier:NCT02355574) and EXPAND (ClinicalTrials.gov identifier:NCT02355587), were initiated under institutional review board approval, and 323 patients with stage I-III CM and median follow-up time of 3.2 years met inclusion criteria. Primary end points were 3-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: The 31-GEP was significant for RFS, DMFS, and OS in a univariate analysis and was a significant, independent predictor of RFS, DMFS, and OS in a multivariable analysis. GEP class 2 results were significantly associated with lower 3-year RFS, DMFS, and OS in all patients and those with stage I-IIA disease. Patients with stage I-IIA CM and a class 2 result had recurrence, distant metastasis, and death rates similar to patients with stage IIB-III CM. Combining 31-GEP results and AJCC staging enhanced sensitivity over each approach alone. CONCLUSION: These data provide a rationale for using the 31-GEP along with AJCC staging, and suggest that patients with stage I-IIA CM and a class 2 31-GEP signature may be candidates for more intense follow-up.

Pediatric stroke associated with a sedentary lifestyle during the SARS-CoV-2 (COVID-19) pandemic: a case report on a 17-year-old.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic-associated quarantine has led to a more sedentary lifestyle in teenagers. This may increase the risk for venous thromboembolism and a subsequent source of an ischemic stroke through a patent foramen ovale (PFO). Here, we report a pediatric stroke case likely due to these factors.

A Heparan Sulfate Device for the Regeneration of Osteochondral Defects.

IMPACT STATEMENT: Repairing damaged joint cartilage remains a significant challenge. Treatment involving microfracture, tissue grafting, or cell therapy provides some benefit, but seldom regenerates lost articular cartilage. Providing a point-of-care solution that is cell and tissue free has the potential to transform orthopedic treatment for such cases. Glycosaminoglycans such as heparan sulfate (HS) are well suited for this purpose because they provide a matrix that enhances the prochondrogenic activities of growth factors normally found at sites of articular damage. In this study, we show the potential of a novel HS device, which is free of exogenous cells or growth factors, in regenerating osteochondral defects.

The Combination of the Tunnel View and Weight-Bearing Anteroposterior Radiographs Improves the Detection of Knee Arthritis.

Imaging used for the evaluation of knee pain has historically included weight-bearing anteroposterior (AP), lateral, and sunrise radiographs. We wished to evaluate the utility of adding the weight-bearing (WB) posteroanterior (PA) view of the knee in flexion. We hypothesize that (1) the WB tunnel view can detect radiographic osteoarthritis (OA) not visualized on the WB AP, (2) the combination of the AP and tunnel view increases the radiographic detection of OA, and (3) this may provide additional information to the clinician evaluating knee pain. We retrospectively reviewed the WB AP and tunnel view radiographs of 100 knees (74 patients) presenting with knee pain and analyzed for evidence of arthritis. The combination of the WB tunnel view and WB AP significantly increased the detection of joint space narrowing in the lateral (p < 0.001) and medial (p = 0.006) compartments over the AP view alone. The combined views significantly improved the identification of medial subchondral cysts (p = 0.022), sclerosis of the lateral tibial plateau (p = 0.041), and moderate-to-large osteophytes in the medial compartment (p = 0.012), intercondylar notch (p < 0.001), and tibial spine (p < 0.001). The WB tunnel view is an effective tool to provide additional information on affected compartments in the painful knee, not provided by the AP image alone.

Imageless computer navigation in total knee arthroplasty provides superior short term functional outcomes: a meta-analysis.

Computer navigation in total knee arthroplasty (TKA) is intended to produce more reliable results, but its impact on functional outcomes has not been firmly demonstrated. Literature searches were performed for Level I randomized trials that compared TKA using imageless computer navigation to those performed with conventional instruments. Radiographic and functional outcomes were extracted and statistically analyzed. TKA performed with computer navigation was more likely to be within 3° of ideal mechanical alignment (87.1% vs. 73.7%, P < .01). Navigated TKAs had a higher increase in Knee Society Score at 3-month follow-up (68.5 vs. 58.1, P = .03) and at 12-32 month follow-up (53.1 vs. 45.8, P < .01). Computer navigation in TKA provides more accurate alignment and superior functional outcomes at short-term follow-up.

Predicting femoral head diameter and lesser trochanter to center of femoral head distance: a novel method of templating hip hemiarthroplasty.

Lesser-trochanter-to-center-of-femoral-head-distance (LTCHD) is commonly used in hip reconstruction. Demographic and radiographic variables were analyzed to predict the LTCHD and femoral head size (FHS). Two hundred twenty six patients after hip arthroplasty and 136 patients after hip hemiarthroplasty (HA) were retrospectively reviewed. Five variables significantly affected the LTCHD and four affected the FHS. For LTCHD, it was relative neck length (RNL), gender, height, race, age and weight. For FHS it was gender, height, age and race. The average predicted LTCHD was within 2.86 mm, and the FHS was 1.63 ± 1.10mm of the intra-operative measurements. By using our regression formulas the LTCHD and FHS can be calculated preoperatively to help improve precision in leg length and offset reconstruction.

Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells.

The interface between bone tissue and metal implants undergoes various types of mechanical loading, such as strain, compression, fluid pressure, and shear stress, from daily activities. Such mechanical perturbations create suboptimal environments at the host bone-implant junction, causing an accumulation of wear particles and debilitating osseous integration, potentially leading to implant failure. While many studies have focused on the effect of particles on macrophages or osteoprogenitor cells, differential and combined effects of mechanical perturbations and particles on such cell types have not been extensively studied. In this study, macrophages and osteoprogenitor cells were subjected to physiological and superphysiological mechanical stimuli in the presence and absence of Ti particles with the aim of simulating various microenvironments of the host bone-implant junction. Macrophages and osteoprogenitor cells were capable of engulfing Ti particles through actin remodeling and also exhibited changes in mRNA levels of proinflammatory cytokines under certain conditions. In osteoprogenitor cells, superphysiological strain increased proinflammatory gene expression; in macrophages, such mechanical perturbations did not affect gene expression. We confirmed that this phenomenon in osteoprogenitor cells occurred via activation of the ERK1/2 signaling pathway as a result of damage to the cytoplasmic membrane. Furthermore, AZD6244, a clinically relevant inhibitor of the ERK1/2 pathway, mitigated particle-induced inflammatory gene expression in osteoprogenitor cells and macrophages. This study provides evidence of more inflammatory responses under mechanical strains in osteoprogenitor cells than macrophages. Phagocytosis of particles and mechanical perturbation costimulate the ERK1/2 pathway, leading to expression of proinflammatory genes.

Effect of femoral offset on pain and function after total hip arthroplasty.

The effects of altering patients' femoral offset (FO) during total hip arthroplasty on postoperative pain and function have not been well described. This study compared clinical outcomes as assessed by the Short Form 12 Health Survey and Western Ontario and McMaster University Osteoarthritis Index between patients who had their FOs restored to varying degrees (compared to the contralateral normal hip [CL]). We retrospectively measured postoperative FOs on standard anteroposterior pelvis radiographs and compared to the CL. Patients were categorized into one of 3 groups: decreased offset (< -5 mm compared to CL), normal offset (between -5 and +5 mm), and increased offset (> +5 mm). The decreased offset group exhibited Western Ontario and McMaster University Osteoarthritis Index Physical Function scores that were less than those of the normal offset and increased offset groups (72.03, 82.23, and 79.51, respectively [P = .019]). In conclusion, reducing a patients' native FO led to inferior functional outcome scores.

Unicompartmental knee arthroplasty relieves pain and improves function more than total knee arthroplasty.

This study compared outcomes as assessed by 12-item Short-Form Health Survey (SF-12) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) between patients who underwent unicompartmental (UKA) and patients who underwent total knee (TKA) arthroplasty. We prospectively collected preoperative demographic and SF-12 and WOMAC data on 128 TKAs and 70 UKAs. Postoperatively, SF-12 and WOMAC outcomes were recorded during annual follow-up visits. At baseline, patients who underwent UKA had a higher Charlson Comorbidity Index than patients who underwent TKA; otherwise, preoperative characteristics were similar. At a mean follow-up of 3.0 years for UKA and 2.9 years for TKA, patients who underwent UKA reported higher SF-12 physical component and mental component scores and WOMAC pain/stiffness/physical function scores (confirmed with multivariate analysis). Furthermore, patients who underwent UKA had significantly larger improvements in both SF-12 outcomes and WOMAC pain and physical function scores from baseline than did patients who underwent TKA.

Molecular analysis of melanoma-induced sentinel lymph node immune dysfunction.

INTRODUCTION: Sentinel lymph nodes (SLNs) of melanoma patients show evidence of tumor-induced immune dysfunction. Our previous works have shown that IL-10 and IFNγ co-regulate indoleamine-2,3-dioxygenase (IDO)-expressing immunosuppressive dendritic cells (DCs) in melanoma SLNs. The goal of this study is to examine the relationship between melanoma SLN tumor burden and the degree of SLN immune dysfunction as a model to study tumor-induced immune dysfunction. We hypothesize that SLN tumor burden correlates with the degree of SLN immune dysfunction. METHODS: Patients undergoing SLN biopsy for clinical stages I and II melanomas were enrolled in the study under an IRB-approved protocol. During the SLN biopsy, non-hot and non-blue portion of the SLN was harvested, flash-frozen in liquid nitrogen, and mRNA was extracted. By using quantitative real-time PCR, gene expressions of cytokines (IL-4, IL-10, IFNγ, TGFß, GM-CSF) and the surrogates of immunosuppressive regulatory and effector cells (IDO-expressing DCs and Foxp3-expressing T-regs, respectively) were measured and correlated against the SLN tumor burden (MART1) and against each other. The data were log transformed for normalization. Statistical test used Student's t-test and stepwise multivariate regression analysis. Statistical significance was determined at P < 0.05. RESULTS: SLNs of 74 patients were analyzed in this analysis. Ten of seventy-four patients (13.5%) had tumor-positive SLNs. MART1 gene expression showed a significant difference between the SLN (+) and SLN (-) groups (P = 0.04). Among the various cytokines, multivariate analysis showed that only IFNγ gene expression correlated independently with MART1 gene expression (P < 0.0001, r = 0.91). Similar multivariate analyses show that IFNγ (P < 0.0001, r = 0.78), IL-10 (P = 0.0037, r = 0.60), and TGFß (P < 0.0001, r = 0.95) gene expressions correlated independently with IDO gene expression. IFNγ (P < 0.0001, r = 0.87) and GM-CSF (P = 0.042, r = 0.76) gene expressions correlated independently with Foxp3 gene expression. MART1 gene expression showed independent correlation with IDO (P = 0.0002, r = 0.75) and Foxp3 (P = 0.0002, r = 0.75) gene expressions. CONCLUSION: SLN tumor burden correlates with immunosuppressive IDO and Foxp3 expressions within the SLNs of melanoma patients. Our data are consistent with our theory that melanoma induces expressions of specific cytokines, which in turn, stimulate immune suppressors within the SLN. This study also supports our previous finding that IL-10 and IFNγ co-regulate IDO within the SLN. In our data, IFNγ is the sole cytokine that correlates with the SLN tumor burden and seems to play a central role in tumor-induced immunological changes in the SLN immune microenvironment.

Prosthetic valve endocarditis: clinicopathological correlates in 122 surgical specimens from 116 patients (1985-2004).

BACKGROUND: Few studies have documented the clinicopathological features of prosthetic valve endocarditis independently of native valve endocarditis. STUDY DESIGN: Retrospective analysis of patients undergoing cardiac surgery for prosthetic valve endocarditis at our institution (1985-2004). METHODS: Medical records and microscopic slides were reviewed from 116 patients for demographics, infecting organisms, comorbidities, and pathologic features. RESULTS: Patients were 12-86 years old (mean, 59 years). Among 122 valves, 64% were from men and 67% were purely regurgitant. Aortic prosthetic valve endocarditis frequently affected men (76%); mitral prosthetic valve endocarditis often affected women (62%). Embolization occurred in 35% and heart failure in 32%. Prevalent predisposing conditions were the prosthetic valve alone (43%) and diabetes mellitus (20%). Prosthetic valve endocarditis was aortic or mitral in 98% and was active in 70%. Annular abscess or paravalvular leak affected mechanical valves more frequently than bioprosthetic (89% vs. 65%; P=.001). Causative organisms (n=116) included Staphylococcus aureus (30%), coagulase-negative staphylococcus (22%), viridans streptococci (18%), enterococci (10%), other streptococci (8%), and other organisms (12%). S. aureus was the most prevalent cause of early-onset (38%) and late-onset (30%) prosthetic valve endocarditis. Coagulase-negative staphylococcus caused early-onset (31%) and most intermediate-onset (40%) disease and had a shorter median implantation-to-infection time than other organisms (6.5 vs. 61.3 months; P<.001). Viridans streptococci and enterococci primarily caused late-onset endocarditis. For active infections by cocci, most cases exhibited strong Gram staining, but four showed only strong Grocott methenamine silver staining. CONCLUSIONS: Cocci accounted for 83% of infections. Early-onset prosthetic valve endocarditis was primarily staphylococcal, and late-onset prosthetic valve endocarditis resembled native valve endocarditis. Both Gram and Grocott methenamine silver stains were necessary to reliably identify organisms microscopically.

Long-term follow-up of basal joint resection arthroplasty of the thumb with transfer of the abductor pollicis brevis origin to the flexor carpi radialis tendon.

PURPOSE: To investigate the long-term functional and clinical outcomes of a tendon transfer during basal joint interposition arthroplasty for osteoarthritis of the basal joint of the thumb, in which the origin of the abductor pollicis brevis (APB) and opponens pollicis is transferred to the flexor carpi radialis tendon, in order to increase the abduction moment arm of the thumb and provide dynamic stabilization of the base of the first metacarpal. METHODS: We observed 22 patients, who received basal joint interposition arthroplasty with APB and opponens pollicis tendon transfer, over an average of 9 years (range, 3-20 years). Subjective outcome measures included patient satisfaction scores, visual analog scale scores for pain, and Disabilities of the Arm, Shoulder and Hand (DASH) scores. Clinical evaluations included thumb range of motion, grip strength, and pinch strength. RESULTS: At an average follow-up of 9 years, 95% of patients (21 out of 22) subjectively scored the procedure as good or excellent and reported improvement in activities of daily living. Mean visual analog scale pain score was 4.4 at rest and 7.8 with activity (out of 100), and mean DASH score was 13.3 (out of 100). Average grip strength of the operated hand was equal to that of the contralateral hand, and lateral and tip pinch strengths were 79% and 93%, respectively, of the contralateral hand. No intraoperative or early postoperative complications were reported, although 1 patient whose procedure was performed as treatment for failed silastic arthroplasty reported metacarpal instability at 9-year follow-up (DASH score of 22). CONCLUSIONS: Basal joint arthroplasty with APB and opponens pollicis tendon transfers provides excellent long-term results for carpometacarpal thumb osteoarthritis. The procedure is safe, with a low complication rate. Its success has long-term durability as measured by patient satisfaction, functional outcome measures, range of motion, and strength. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Biological factors, tumor growth kinetics, and survival after metastasectomy for pulmonary melanoma.

INTRODUCTION: Approximately 23% of melanoma patients will eventually develop pulmonary metastases and have a median survival of only about 7-11 months. Because pulmonary metastasectomy can improve this statistic, we investigated clinicopathologic features and biological correlates that might be used to identify surgical candidates. METHODS: Archived operative specimens and clinical records were retrieved for 20 melanoma patients who underwent resection of isolated pulmonary metastases at the John Wayne Cancer Institute, Saint John's Health Center. Five-year postmetastasectomy survival (PMS) rate was correlated with age, number of pulmonary metastases, tumor doubling time (TDT), tumor necrosis, and immunohistochemical expressions of four biological markers: Ki-67, glucose transporter-1 (Glut-1), caspase-3, and CD31. RESULTS: Median TDT was 61 days. On multivariate analysis, TDT (P = 0.008), Glut-1 intensity (P = 0.04), and CD31 expression (P = 0.004) were the significant predictors of PMS. Age, number of pulmonary metastases, tumor necrosis, and expression of Ki-67 or caspase-3 did not significantly impact survival. Median TDT was 56 days with Glut-1 expression versus 165 days without Glut-1 expression (P = 0.002), and Glut-1 staining intensity independently affected TDT (P = 0.012). CONCLUSIONS: Surgical resection may be preferable to toxic systemic therapies in melanoma patients whose isolated pulmonary metastases have a long TDT (> or = 61 days) and no biopsy evidence of Glut-1 expression.

A phase 0 trial of riluzole in patients with resectable stage III and IV melanoma.

PURPOSE: Ectopic expression of GRM1 in murine melanocytes results in transformation into a form of melanoma, and more than 60% of human melanoma samples tested ectopically express GRM1. Stimulation of this receptor in vitro results in up-regulation of activated extracellular signal-regulated kinase (ERK). Furthermore, a xenograft model of melanoma treated with riluzole, an oral GRM1 blocking agent, showed decreased tumor growth compared with the untreated controls. We have now completed a phase 0 trial of riluzole in patients with melanoma. EXPERIMENTAL DESIGN: Patients enrolled on this trial underwent a pretreatment biopsy, took 200 mg of oral riluzole per day for 14 days, and then underwent resection of their remaining tumor. We compared the levels of pERK and pAKT in the pretreatment and post-treatment samples and assessed the metabolic activity of pretreatment and post-treatment tumors using fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. RESULTS: We accrued 12 patients and all expressed GRM1. We found a significant decrease in pAKT and/or pERK in post-treatment tumor samples as compared with pretreatment samples in 4 (34%) patients. These four patients had a significant decrease in FDG-PET intensity post-treatment as well. Two other patients had a clinical response with no corresponding metabolic response; five patients had similar pretreatment and post-treatment FDG-PET scan findings; and one patient had progressive disease. CONCLUSIONS: Our data show that glutamate blockade with riluzole can inhibit signaling through the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT pathways and suppress the metabolic activity of melanoma. The ectopic expression of metabotropic glutamate receptors may be important in the pathogenesis of human melanoma, and targeting this pathway may be an effective therapy.

Assessment of bone perfusion with contrast-enhanced magnetic resonance imaging.

Osteoarthritis and avascular necrosis are common clinical entities with unknown origins. Recently, vascular changes were implicated in the pathogenesis of both conditions. This article discusses the use of novel noninvasive imaging techniques as a means of assessing bone perfusion and quantifying differences seen in osteoarthritis and avascular necrosis. Review of our human data suggests that the MRI contrast dye is retained for longer periods of time, suggesting decreased perfusion out of regions of osteoarthritis and avascular necrosis. Use of such a noninvasive measure of assessing bone perfusion could be useful in the diagnosis, prevention, and treatment of not only osteoarthritis and avascular necrosis but also other entities that affect the musculoskeletal system.

Real-time PCR vs standard culture detection of group A beta-hemolytic streptococci at various anatomic sites in tonsillectomy patients.

OBJECTIVE: To compare rates of group A beta-hemolytic streptococci (GABHS) detection by real-time polymerase chain reaction (rtPCR) and standard culture (SCx) at different anatomic sites to determine whether a more patient-friendly site (eg, retromolar trigone or gingivobuccal sulcus) would yield results similar to the tonsillar surface. Real-time polymerase chain reaction can detect GABHS at rates equal to SCx, and results require only a few hours. DESIGN: Prospective study. SETTING: Tertiary care setting. PATIENTS: The study population comprised 130 patients undergoing tonsillectomy or adenotonsillectomy. INTERVENTION: At tonsillectomy, swabs were taken of pharyngeal tonsil surface, pharyngeal tonsillar core, inferior gingivobuccal sulcus, and retromolar trigone. Tissue samples were taken from tonsil core and adenoid. All comparisons between methods and sites were made using the McNemar test for comparing correlated proportions. All calculated P values were 2-sided. MAIN OUTCOME MEASURE: Detection of GABHS by rtPCR and SCx. RESULTS: In 41 cases (32%), GABHS was detected at 1 or more sampled sites, and 29 of those positive were detected on the tonsil surface-SCx and rtPCR results were both positive in 28 (97%). Of these 29 cases, results from the gingivobuccal site were positive by both rtPCR and SCx in 4 (14%), rtPCR only in 3 (10%), and SCx only in 3 (10%). Of the 7 tonsil surface-positive cases with retromolar trigone swabs, results were positive by rtPCR only in 1 (14%) and SCx only in 2 (29%). CONCLUSION: Whether rtPCR or SCx is used, swabs of gingivobuccal sulcus and retromolar trigone do not accurately reflect GABHS populations on the tonsil surface.

Hylan versus corticosteroid versus placebo for treatment of basal joint arthritis: a prospective, randomized, double-blinded clinical trial.

PURPOSE: Conservative, nonsurgical therapies for basal joint osteoarthritis, such as thumb spica splinting and intra-articular corticosteroid injections, remain the mainstays for symptomatic treatment. This study compares intra-articular hylan, corticosteroid, and placebo injections with regard to pain relief, strength, symptom improvement, and metrics of manual function in a randomized, controlled, double-blinded study. METHODS: Sixty patients with basal joint arthritis were randomized to receive 2 intra-articular hylan injections 1 week apart, 1 placebo injection followed by 1 corticosteroid injection 1 week later, or 2 placebo injections 1 week apart. Patients were evaluated at 2, 4, 12, and 26 weeks and assessed with Visual Analog Scale pain scores, strength measures, difference scores, Disabilities of the Arm, Shoulder, and Hand (DASH) scores, and range of motion measurements. RESULTS: All groups reported pain relief at 2 weeks. The steroid and placebo groups had significantly less pain at week 4 compared with baseline, but this effect disappeared by week 12. Only hylan injections continued to provide pain relief at 12 and 26 weeks compared with baseline. There were no significant differences in pain between groups at any time. At 12 and 26 weeks, the hylan group had improved grip strength compared with baseline, whereas the steroid and placebo groups were weaker. At 4 weeks, the steroid group reported in the difference score a greater improvement in symptoms (68%) compared with the hylan (44%) and placebo (50%) groups. Whereas at 26 weeks the hylan group reported the largest improvement in symptoms (68%), this was not statistically different from the placebo (47%) and steroid (58%) groups. There were no significant differences in Disabilities of the Arm, Shoulder, and Hand scores or range of motion among the groups. There were no complications from any injection. CONCLUSIONS: There were no statistically significant differences among hylan, steroid, and placebo injections for most of the outcome measures at any of the follow-up time points. However, based on the durable relief of pain, improved grip strength, and the long-term improvement in symptoms compared with preinjection values, hylan injections should be considered in the management of basal joint arthritis of the thumb. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Monocyte-derived IL-10 expression predicts prognosis of stage IV melanoma patients.

There are no standard methods to predict response to treatment or outcome of stage IV melanoma. Our previous assessment of peripheral blood mononuclear cells (PBMC) from immunized patients demonstrated that interleukin (IL)-10 expression might be associated with prognosis. However, PBMC are a mixture of CD4+ cells, CD8+ cells, and monocytes. This study identified the subset of PBMC responsible for IL-10 expression and evaluated the prognostic value of IL-10 expression in immunized stage IV patients. Eighty-seven patients with stage IV melanoma were randomly selected from our database. All patients had received an allogeneic melanoma whole-cell vaccine (Canvaxin) after complete resection of clinical disease. Blood samples had been collected serially during Canvaxin administration and cryopreserved. Intracellular IL-10 expression was assessed by double staining fluorescence-activated cell sorter. CD14+ monocytes are the predominant PBMC producing IL-10. Sixteen weeks after treatment (week 16), IL-10 levels were significantly (P=0.02) higher in poor-survival patients than those with favorable outcomes. Patients were separated into 2 groups on the basis of the CD14+ monocyte IL-10 response: either increasing or decreasing IL-10 expression from preimmunization (week 0) to week 16 blood draws. Patients with increasing IL-10 levels had significantly shorter survival than those whose IL-10 levels decreased at week 16 (P<0.0001). Multivariate analysis demonstrated that trends in IL-10 levels inversely correlated with survival (P<0.0001). We conclude that CD14+ monocytes are the dominant cellular source of IL-10 among PBMC and that changes in IL-10 expression may serve as an immunologic-based surrogate for predicting outcome for stage IV patients after surgical resection.

Molecular characterization of inflammatory genes in sentinel and nonsentinel nodes in melanoma.

PURPOSE: Identification of regional node metastasis is important for accurate staging and optimal treatment of early melanoma. We hypothesize that the nodal profile of immunoregulatory cytokines can confirm the identity of the first tumor-draining regional node, i.e., the sentinel node (SN) and indicate its tumor status. EXPERIMENTAL DESIGN: RNA was extracted from freshly dissected and preserved nodal tissue of 13 tumor-negative SNs, 10 tumor-positive SNs (micrometastases <2 mm), and 11 tumor-negative non-SNs (NSN). RNA was converted into cDNA and then amplified by PCR. Expression of 96 cytokines and chemokines was assessed using cDNA microarray and compared by using hierarchical clustering. RESULTS: Fifty-seven genes were expressed at significantly (P < 0.05) different levels in SNs and NSNs (4 genes had higher expression, and 53 genes had lower expression in SNs). Expression levels of interleukin-13 (IL-13), leptin, lymphotoxin beta receptor (LTbR), and macrophage inflammatory protein 1b (MIP1b) were significantly higher (P < 0.04, P < 0.01, P < 0.05, and P < 0.01, respectively), and expression level of IL-11Ra was lower (P < 0.03) for tumor-positive as compared with tumor-negative SN. Receiver-operator characteristics curve analyses showed that the area under the curve (AUC) for IL-13, leptin, LTbR, MIP1b, and IL-11Ra was 0.79, 0.83, 0.75, 0.81, and 0.77, respectively. The AUC for the five genes in combination was 0.973, suggesting high concordance of gene-expression profiles with SN staging. CONCLUSIONS: SNs have a different immunoregulatory cytokine profile than NSNs. The cytokine profile of tumor-positive SNs; increased expression of IL-13, leptin, LTbR, and MIP1b and decreased expression of IL-11Ra, may provide clues to the local tumor lymph node interaction seen in the earliest steps of melanoma metastasis.