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Topical vancomycin and its effect on survival and migration of osteoblasts, fibroblasts, and myoblasts: An in vitro study

Liu, James X; Bravo, Dalibel; Buza, John; Kirsch, Thorsten; Kennedy, Oran; Rokito, Andrew; Zuckerman, Joseph D; Virk, Mandeep S
The purpose of this study was to examine the influence of topical vancomycin on cell migration and survival of tissue healing cells. Human osteoblasts, myoblasts and fibroblasts were exposed to vancomycin at concentrations of 1, 3, 6, or 12 mg/cm2 for either a 1-h or 48-h (continuous) duration. Continuous exposure to all vancomycin concentrations significantly reduced cell survival (<22% cells survived) and migration in osteoblasts and myoblasts (P < 0.001). 1-h vancomycin exposure reduced osteoblast and myoblast survival and migration only at 12 mg/cm2 (P < 0.001). Further in vivo studies are warranted to optimize the dosage of intrawound vancomycin.
PMCID:5895903
PMID: 29657439
ISSN: 0972-978x
CID: 3040782

Treatment for Symptomatic SLAP Tears in Middle-Aged Patients Comparing Repair, Biceps Tenodesis, and Nonoperative Approaches: A Cost-Effectiveness Analysis

Paoli, Albit R; Gold, Heather T; Mahure, Siddharth A; Mai, David H; Agten, Christoph A; Rokito, Andrew S; Virk, Mandeep S
PURPOSE/OBJECTIVE:To evaluate the cost-effectiveness of nonoperative management, primary SLAP repair, and primary biceps tenodesis for the treatment of symptomatic isolated type II SLAP tear. METHODS:A microsimulation Markov model was constructed to compare 3 strategies for middle-aged patients with symptomatic type II SLAP tears: SLAP repair, biceps tenodesis, or nonoperative management. A failed 6-month trial of nonoperative treatment was assumed. The principal outcome measure was the incremental cost-effectiveness ratio in 2017 U.S. dollars using a societal perspective over a 10-year time horizon. Treatment effectiveness was expressed in quality-adjusted life-years (QALY). Model results were compared with estimates from the published literature and were subjected to sensitivity analyses to evaluate robustness. RESULTS:Primary biceps tenodesis compared with SLAP repair conferred an increased effectiveness of 0.06 QALY with cost savings of $1,766. Compared with nonoperative treatment, both biceps tenodesis and SLAP repair were cost-effective (incremental cost-effectiveness ratio values of $3,344/QALY gained and $4,289/QALY gained, respectively). Sensitivity analysis showed that biceps tenodesis was the preferred strategy in most simulations (52%); however, for SLAP repair to become cost-effective over biceps tenodesis, its probability of failure would have to be lower than 2.7% or the cost of biceps tenodesis would have to be higher than $14,644. CONCLUSIONS:When compared with primary SLAP repair and nonoperative treatment, primary biceps tenodesis is the most cost-effective treatment strategy for type II SLAP tears in middle-aged patients. Primary biceps tenodesis offers increased effectiveness when compared with both primary SLAP repair and nonoperative treatment and lower costs than primary SLAP repair. LEVEL OF EVIDENCE/METHODS:Level III, economic decision analysis.
PMID: 29653794
ISSN: 1526-3231
CID: 3037462

Comparison Between Image-Guided and Landmark-Based Glenohumeral Joint Injections for the Treatment of Adhesive Capsulitis: A Cost-Effectiveness Study

Gyftopoulos, Soterios; Abballe, Valentino; Virk, Mandeep S; Koo, James; Gold, Heather T; Subhas, Naveen
OBJECTIVE:The purpose of this study was to determine the cost-effectiveness of landmark-based and image-guided intraarticular steroid injections for the initial treatment of a population with adhesive capsulitis. MATERIALS AND METHODS/METHODS:A decision analytic model from the health care system perspective over a 6-month time frame for 50-year-old patients with clinical findings consistent with adhesive capsulitis was used to evaluate the incremental cost-effectiveness of three techniques for administering intraarticular steroid to the glenohumeral joint: landmark based (also called blind), ultrasound guided, and fluoroscopy guided. Input data on cost, probability, and utility estimates were obtained through a comprehensive literature search and from expert opinion. The primary effectiveness outcome was quality-adjusted life years (QALY). Costs were estimated in 2017 U.S. dollars. RESULTS:Ultrasound-guided injections were the dominant strategy for the base case, because it was the least expensive ($1280) and most effective (0.4096 QALY) strategy of the three options overall. The model was sensitive to the probabilities of getting the steroid into the joint by means of blind, ultrasound-guided, and fluoroscopy-guided techniques and to the costs of the ultrasound-guided and blind techniques. Two-way sensitivity analyses showed that ultrasound-guided injections were favored over blind and fluoroscopy-guided injections over a range of reasonable probabilities and costs. Probabilistic sensitivity analysis showed that ultrasound-guided injections were cost-effective in 44% of simulations, compared with 34% for blind injections and 22% for fluoroscopy-guided injections and over a wide range of willingness-to-pay thresholds. CONCLUSION/CONCLUSIONS:Ultrasound-guided injections are the most cost-effective option for the initial steroid-based treatment of patients with adhesive capsulitis. Blind and fluoroscopy-guided injections can also be cost-effective when performed by a clinician likely to accurately administer the medication into the correct location.
PMID: 29629805
ISSN: 1546-3141
CID: 3037172

Multilevel glenoid morphology and retroversion assessmentinwalchb2 and b 3types [Meeting Abstract]

Samim, M; Virk, M; Zuckerman, J; Gyftopoulos, S
Purpose: As glenohumeral osteoarthritis progresses, there is increased risk for posterior glenoid bone loss which impacts an increasingly common treatment for these patients, total shoulder arthroplasty. Defining the level of maximum posterior bone loss and accurate assessment of its severity, using glenoid version measurements, are crucial to correctly align the glenoid prosthesis with glenoid to prevent prosthetic failure. While the importance of this information is clear, how these measurements should be performed remains in question with several techniques described in the literature. The purpose of this study was to define the most accurate level to measure glenoid version on CT for the most clinically relevant variants of posterior glenoid bone loss, Walch B2 and B3 types. Materials and Methods: 386 consecutive CT shoulder studies performed for shoulder arthroplasty preoperative planning between 2013- 2016 were retrospectively reviewed. Patients with B2 and B3 glenoid types were included. Two radiologists measured glenoid retroversion independently according to Friedman method on true axial CT images using the "intermediate glenoid line", at three glenoid heights: 25% (upper) 50% (equator) and 75% (lower). Results: 29 B2 and 8 B3 glenoid types were included. There was no statistically significant difference found in the retroversion measurements performed by each reader at the three glenoid levels on the B2 or B3 glenoid types (Mean angles (%) in upper, equator and lower in B2: 16.5, 17,0 and 17.5 and B3: 20.6, 20.7 and 23.2, respectively). There was substantial inter-reader correlation (r>=0.7) in angle measurements. Conclusion: Our study suggests that glenoid version can be accurately measured at any level between 25%-75%of the glenoid height forWalch B2 and B3 types. We recommend that the glenoid equator be used as the reference in order to assure consistent and reliable version measurements in this group of patients
EMBASE:620615481
ISSN: 1432-2161
CID: 2959312

Patient Preference Before and After Arthroscopic Rotator Cuff Repair: Which Is More Important, Pain Relief or Strength Return?

Virk, Mandeep S; Levy, David M; Kuhns, Benjamin D; Krecher, James S; Parsley, Billy K; Burkhart, Stephen S; Romeo, Anthony A; Verma, Nikhil N; Cole, Brian J
Our understanding of patients' desired outcomes and expectations of arthroscopic rotator cuff repair (ARCR) is limited, particularly regarding the importance of pain relief and strength return relative to each other. We conducted a study of patient's ratings of the importance of pain relief and strength return after ARCR. Before undergoing surgery, 60 patients completed a shoulder questionnaire on which they assessed severity of symptoms and rated, on a 10-point scale, the importance of postoperative improvements in pain relief and strength return. After surgery, they completed the same questionnaire, again rating the importance of pain relief and strength return. About 50% of the patients valued pain relief and strength return equally before and after ARCR. However, overall patient ratings were higher for strength return over pain relief, both before surgery, mean (SD), 9.2 (2.1) vs 8.6 (2.3) (P = .02), and afterward, at a follow-up of 5.2 (0.2) years, 8.9 (1.9) vs 8.2 (3.1) (P = .03). This significant preference for strength return held irrespective of sex, age, active sports involvement, preoperative self-assessed pain score, and subjective shoulder weakness. Before surgery, increasing age was associated with a stronger preference for pain relief (r = 0.33, P = .01), and retirees preferred pain relief over strength return. These results show the patterns of patient preference for pain relief and strength return after ARCR. Improved understanding of these patients' expectations will allow meaningful changes in patient satisfaction.
PMID: 28856356
ISSN: 1934-3418
CID: 3070582

+/- the cytotoxicity profile of vancomycin hydrochloride on proliferating osteoblasts, fibroblasts, and myoblasts [Meeting Abstract]

Liu, J X; Buza, J; Kirsch, T; Kennedy, O D; Rokito, A S; Zuckerman, J D; Virk, M
Purpose: The intrawound application of lyophilized vancomycin has been reported to significantly decrease the rates of perioperative infection in arthroplasty and spine procedures. The local effect of clinically used supra-therapeutic concentration of intra wound vancomycin on surrounding healing tissue has been a topic of continued investigation. The purpose of this study was to examine the in vitro cytotoxicity profile of vancomycin hydrochloride on osteoblasts, fibroblast, and myoblasts. Methods: Human primary osteoblasts (Lonza), fibroblasts (Lonza), and myoblasts (DV Biologics) were expanded and passaged in sterile polystyrene tissue culture flasks and plated at a density of 10,000 cells/cm2. Cells were exposed to vancomycin hydrochloride (Sigma-Aldrich) at concentrations of 1, 3, 6, or 12 mg/cm2. To assess the effect of vancomycin on cell migration, a scratch assay was performed, in which a "scratch" was made in a cell monolayer following vancomycin exposure, and images were subsequently captured at regular intervals until cellular closure of the scratch. Cell survival was measured 48 hours post-vancomycin exposure using a cell cytotoxicity assay (Cell Counting Kit-8, Dojindo). Results: Vancomycin concentrations greater than or equal to 1 mg/cm2 decreased survival of myoblasts and osteoblasts to less than 11% relative to control. Vancomycin greater than or equal to 3 mg/ cm2 decreased fibroblast survival to less than 8% relative to control (Fig. 1). Vancomycin concentrations of 1 mg/cm2 did not significantly affect the survival of fibroblasts. Closure of the scratch defect was observed in less than 24 hours for all control conditions. In myoblasts and osteoblasts, the scratch defect remained open indefinitely following exposure to vancomycin concentrations greater than or equal to 1 mg/cm2. Closure of the scratch defect in fibroblasts was observed in less than 36 hours following exposure to vancomycin of 1 mg/cm2, and remained opened indefinitely following exposure to vancomycin greater than or equal to 3 mg/cm2. Conclusions: Vancomycin has a significant cytotoxic effect on proliferating osteoblasts and myoblasts at concentrations greater than (Figure Presented) or equal to 1 mg/cm2.Vancomycin has a pronounced cytotoxic effect on fibroblasts at concentrations greater than or equal to 3 mg/cm2. Further in vivo studies are warranted to investigate the effect of high local concentrations of vancomycin on infection, bony fusion, and wound healing
EMBASE:619247637
ISSN: 1532-6500
CID: 2860482

Cost-effectiveness of magnetic resonance imaging versus ultrasound for the detection of symptomatic full-thickness supraspinatus tendon tears

Gyftopoulos, Soterios; Guja, Kip E; Subhas, Naveen; Virk, Mandeep S; Gold, Heather T
BACKGROUND: The purpose of this study was to determine the value of magnetic resonance imaging (MRI) and ultrasound-based imaging strategies in the evaluation of a hypothetical population with a symptomatic full-thickness supraspinatus tendon (FTST) tear using formal cost-effectiveness analysis. METHODS: A decision analytic model from the health care system perspective for 60-year-old patients with symptoms secondary to a suspected FTST tear was used to evaluate the incremental cost-effectiveness of 3 imaging strategies during a 2-year time horizon: MRI, ultrasound, and ultrasound followed by MRI. Comprehensive literature search and expert opinion provided data on cost, probability, and quality of life estimates. The primary effectiveness outcome was quality-adjusted life-years (QALYs) through 2 years, with a willingness-to-pay threshold set to $100,000/QALY gained (2016 U.S. dollars). Costs and health benefits were discounted at 3%. RESULTS: Ultrasound was the least costly strategy ($1385). MRI was the most effective (1.332 QALYs). Ultrasound was the most cost-effective strategy but was not dominant. The incremental cost-effectiveness ratio for MRI was $22,756/QALY gained, below the willingness-to-pay threshold. Two-way sensitivity analysis demonstrated that MRI was favored over the other imaging strategies over a wide range of reasonable costs. In probabilistic sensitivity analysis, MRI was the preferred imaging strategy in 78% of the simulations. CONCLUSION: MRI and ultrasound represent cost-effective imaging options for evaluation of the patient thought to have a symptomatic FTST tear. The results indicate that MRI is the preferred strategy based on cost-effectiveness criteria, although the decision between MRI and ultrasound for an imaging center is likely to be dependent on additional factors, such as available resources and workflow.
PMID: 28893546
ISSN: 1532-6500
CID: 2702162

Povidone-iodine Solutions Inhibit Cell Migration and Survival of Osteoblasts, Fibroblasts, and Myoblasts

Liu, James X; Werner, Jordan A; Buza, John A 3rd; Kirsch, Thorsten; Zuckerman, Joseph D; Virk, Mandeep S
STUDY DESIGN: In vitro laboratory study. OBJECTIVE: The purpose of this study was to identify the effect of dilute povidone-iodine (PVI) solutions on human osteoblast, fibroblast and myoblast cells in vitro. SUMMARY OF BACKGROUND DATA: Dilute PVI wound lavage has been used successfully in spine and joint arthroplasty procedures to prevent post-operative surgical site infection, but their biologic effect on host cells is largely unknown. METHODS: Human primary osteoblasts, fibroblasts, and myoblasts were expanded in cell culture and subjected to various concentrations of PVI (0%, 0.001%, 0.01%, 0.1%, 0.35%, 1%) for 3 minutes. To assess the effect of PVI on cell migration, a scratch assay was performed, in which a "scratch" was made by a standard pipette tip in a cell monolayer following PVI exposure, and time to closure of the scratch was evaluated. Cell survival and proliferation was measured 48 hours post-PVI exposure using a cell viability and cytotoxicity assay. RESULTS: Closure of the scratch defect in all cell monolayers was achieved in < 24 hours in untreated controls and following exposure to PVI concentrations < 0.1%. The scratch defect remained open indefinitely following exposure to PVI concentrations of >/= 0.1%. PVI concentrations < 0.1% did not have significant effect on survival rates compared with control for all cell types. Cells exposed to PVI >/= 0.1% had cell survival rates of less than 6% (p < 0.05). CONCLUSIONS: Clinically used concentration of PVI (0.35%) exerts a pronounced cytotoxic effect on osteoblasts, fibroblast, and myoblasts in vitro. Further investigation is required to systematically study the effect of PVI on tissue healing in vivo and also determine a safe and clinically potent concentration for PVI lavage. LEVEL OF EVIDENCE: N/A.
PMID: 28505031
ISSN: 1528-1159
CID: 2562672

Cost-effectiveness of MRI versus ultrasound for the detection of full-thickness rotator cuff tendon tears [Meeting Abstract]

Gyftopoulos, S; Guja, K; Virk, M; Subhas, N
Purpose: The optimal diagnostic imaging strategy for a suspected full-thickness rotator cuff tendon tear is controversial, in large part due to the significant up-front cost difference between magnetic resonance imaging (MRI) and ultrasound. Our objective was to compare the cost-effectiveness within the United States health care system of MRI versus ultrasound for initial imaging of patients with a suspected full-thickness rotator cuff tendon tear, and to determine the drivers of cost-effectiveness using sensitivity analysis. Materials and Methods: An expected-value decision analysis with rollback was utilized to compare the costs and outcomes of patients with a suspected full-thickness rotator cuff tendon tear who underwent either MRI, ultrasound, or ultrasound followed by MRI. A comprehensive literature search and expert opinion provided input data on probability estimates, event rates, costs, and health utility states for our model. All costs and benefits were considered from a societal perspective, and discounted at a 3% rate, to reflect the lower value of a delayed expense and the higher value of an earlier benefit. One-way sensitivity analyses were performed to test model robustness, followed by threshold analysis of all variables found to be sensitive. The primary outcomes assessed were costs in 2016 US dollars, effectiveness in quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results: Expected costs per patient were lowest for ultrasound ($1,896), followed by ultrasound-MRI combined ($1,954), and MRI alone ($2,090). MRI was the most effective, providing 1.3410 QALYs, compared to ultrasound (1.3308 QALYs) and MRI after ultrasound (1.3317 QALYs). Ultrasound was the most cost-effective imaging strategy, as reflected by its lower cost/effectiveness ratio ($1425 per QALY) when compared to MRI after ultrasound ($1,467/QALY) and MRI ($1,559/ QALY). The incremental cost-effectiveness ratio for MRI was $18,951 per QALY gained, below the conventional willingness-to-pay threshold of $50,000 (WHO recommendation). The combination of MRI after ultrasound was not cost-effective (ICER $61,075 per QALY gained). Sensitivity analysis revealed that our model was sensitive only to the costs of MRI and ultrasound. Subsequent threshold analysis indicated that MRI remains cost-effective when the average cost for an MRI is less than $660. Moreover, if the cost for MRI falls below $148, or the cost for ultrasound rises above $379, MRI becomes both less costly and more effective than ultrasound, and thus the most cost-effective strategy. Conclusion: Our model showed that ultrasound had an expected cost that was $194 lower than MRI, but MRI was more effective than ultrasound by 0.0102 QALYs. Overall, ultrasound was the most cost-effective imaging strategy. For the base case, there was an ICER of $18,951 per QALY gained for MRI, well below the accepted threshold of $50,000 per QALY gained. Taken together, our results show that both ultrasound and MRI can be cost-effective imaging options to evaluate the patient suspected of a full thickness rotator cuff tendon tear
EMBASE:614350298
ISSN: 1432-2161
CID: 2454352

Coracoid bypass procedure: surgical technique for coracoclavicular reconstruction with coracoid insufficiency

Virk, Mandeep S; Lederman, Evan; Stevens, Christopher; Romeo, Anthony A
BACKGROUND: Failed acromioclavicular (AC) joint reconstruction secondary to a coracoid fracture or insufficiency of the coracoid is an uncommon but challenging clinical situation. We describe a surgical technique of revision coracoclavicular (CC) reconstruction, the coracoid bypass procedure, and report short-term results with this technique in 3 patients. METHODS: In the coracoid bypass procedure, reconstruction of the CC ligaments is performed by passing a tendon graft through a surgically created bone tunnel in the scapular body (inferior to the base of the coracoid) and then fixing the graft around the clavicle or through bone tunnels in the clavicle. Three patients treated with this technique were retrospectively reviewed. RESULTS: AC joint reconstruction performed for a traumatic AC joint separation failed in the 3 patients reported in this series. The previous procedures were an anatomic CC reconstruction in 2 patients and a modified Weaver-Dunn procedure in 1 patient. The coracoid fractures were detected postoperatively, and the mean interval from the index surgery to the coracoid bypass procedure was 8 months. The patients were a mean age of 44 years, and average follow-up was 21 months. At the last follow-up, all 3 patients were pain free, with full range of shoulder motion, preserved CC distance, and a stable AC joint. CONCLUSION: The coracoid bypass procedure is a treatment option for CC joint reconstruction during revision AC joint surgery in the setting of a coracoid fracture or coracoid insufficiency.
PMID: 27989719
ISSN: 1532-6500
CID: 2374232