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  • Patients Who Return to Sport After Primary Anterior Cruciate Ligament Reconstruction Have Significantly Higher Psychological Readiness: A Systematic Review and Meta-analysis of 3744 Patients Am J Sports Med Xiao, M., van Niekerk, M., Trivedi, N., Hwang, C., Sherman, S., Safran, M., Abrams, G. 2022
  • High Specialization among Female Youth Soccer Players Is Associated with an Increased Likelihood of Serious Injury. Medicine and science in sports and exercise Xiao, M., Lemos, J. L., Hwang, C. E., Sherman, S. L., Safran, M. R., Abrams, G. D. 2021

    Abstract

    PURPOSE: To assess the associations between serious injury (> 3-month time loss) and level of specialization among high-level female soccer players and to compare the specialization and college commitment ages of female youth soccer players to Division I college and professional soccer athletes.METHODS: Youth, college, and professional female soccer players in the United States playing in the top league at each level were recruited to complete an anonymous online survey. The survey collected information about player demographics, soccer specialization and training patterns, history of serious injuries from soccer, and perceptions surrounding soccer specialization. Comparisons between groups were performed using 2-sample t-tests, chi-squared analyses, and multiple logistic regression models controlling for differences in age. A p-value of less than 0.05 was set as significant.RESULTS: A total of 1,018 (767 youth, 251 college/professional) athletes completed the survey. Serious injuries affected 23.6% of youth and 51.4% of college/professional athletes. Anterior cruciate ligament (ACL) tears were more prevalent in college/professional players compared to youth athletes (18.3% vs 4.0%; p < 0.001). Highly specialized youth athletes (66.5%) were more likely to have sustained a serious injury from soccer compared to athletes with low specialization (Odds Ratio (OR) = 2.28 [1.38-3.92]; p=0.008) but not moderate specialization (OR = 1.37 [0.83-2.27]; p=0.43). A higher proportion of youth athletes specialized at a young age (< 10 years) compared to college/professional players (44.2% vs 25.9%; p < 0.001).CONCLUSION: High specialization in female youth soccer players is associated with an increased likelihood of sustaining a serious injury. Current youth soccer players are specializing earlier and committing to play college soccer at a younger age compared to when current college and professional players did.

    View details for DOI 10.1249/MSS.0000000000002693

    View details for PubMedID 33927169

  • Pain Management in Shoulder Arthroplasty: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Journal of shoulder and elbow surgery Xiao, M., Cohen, S. A., Cheung, E. V., Freehill, M. T., Abrams, G. D. 2021

    Abstract

    Postoperative pain management after total shoulder arthroplasty (TSA) can be challenging. Given the variety of pain management options available, the purpose of this investigation was to systematically review the literature for randomized controlled trials (RCTs) reporting on pain control after shoulder arthroplasty. We sought to determine which modalities are most effective in managing postoperative pain and reducing postoperative opioid use.A systematic review was performed using PRISMA guidelines. PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for Level I-II RCTs that compared interventions for postoperative pain control after TSA. Pain control measures included nerve blocks and nerve block adjuncts, local injections, patient-controlled analgesia, oral medications, or other modalities. The two primary outcome measures were pain level measured on a 0-10 visual analog scale (VAS) and opioid use. The risk of study bias and methodological quality was analyzed using the Cochrane Collaboration's Risk of Bias 2 (RoB 2) tool. Network meta-analyses were performed for pain VAS at post-surgical timepoints and opioid use using a frequentist approach and random effects model, with heterogeneity quantified using the I2 statistic. Treatments were ranked using the P-score, and statistical significance was set at p < 0.05.The initial search yielded 2391 articles (695 duplicates, 1696 screened, 35 full-text review). Eighteen articles (1358 shoulders; 51% females; mean age range 65 to 73.7 years; four low risk, 12 some risk, and two high risk of bias studies) were included and analyzed. At 4 and 8 hours postoperatively, patients receiving local liposomal bupivacaine (LB) (p < 0.001 for 4 and 8 hours) or local ropivacaine injection (p < 0.001 for 4 hours; p = 0.019 for 8 hours) had significantly more pain compared to patients who received either a continuous (cISB) or single-shot interscalene block (ssISB). No differences (at p<0.05) in opioid use were detected between modalities. P-scores of treatments demonstrated that ssISBs were most favorable at timepoints <24 hours, whereas pain at 24 and 48 hours after surgery was best managed with cISBs or a combination of ssISB with local LB injection.ISBs are superior to local injection alone at managing pain after TSA. ssISBs are optimal for reducing early postoperative pain (< 24 hours), whereas pain at 24 to 48 hours after surgery may be best managed with cISBs or a combination of ssISBs with local LB injection.

    View details for DOI 10.1016/j.jse.2021.06.008

    View details for PubMedID 34284094

  • Surgeon practice patterns for pre-soaking ACL tendon grafts in vancomycin: a survey of the ACL study group. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA Xiao, M., Sherman, S. L., Safran, M. R., Abrams, G. D. 2020

    Abstract

    PURPOSE: To survey members of The ACL study group to determine the current practice patterns surrounding the technique of pre-soaking ACL grafts in vancomycin.METHODS: A web-based questionnaire was distributed to members of the ACL Study Group. Questions included the use of vancomycin solution for graft soaking during ACL reconstruction, their protocol for soaking the graft, vancomycin concentration utilized, graft choices, and concerns with the technique.RESULTS: Sixty-six (57%) ACL surgeons completed the survey. Approximately one-third (37.9%) of respondents currently pre-soak their ACL grafts in vancomycin prior to implantation, with 60% of these surgeons being from Europe. Seventy-six percent have adopted this practice within the past 5years. The majority of surgeons wrap the graft in a vancomycin-soaked gauze prior to implantation (56%), soak for a variable amount of time before implantation (56%), use a concentration of 5mg/mL (68%), and soak hamstring grafts (92%). Concerns included the mechanical properties of the graft (35%), cost of vancomycin (23%), availability (12%), and antibiotic resistance (9%).CONCLUSION: This survey demonstrates that 37.9% of ACL study group members currently utilize vancomycin to pre-soak ACL tendon grafts as a means to decrease post-operative infection risk, with the majority of surgeons having implemented this practice within the past 5years. The biggest concern towards using vancomycin was the mechanical properties of the graft after soaking.LEVEL OF EVIDENCE: IV.

    View details for DOI 10.1007/s00167-020-06265-1

    View details for PubMedID 32902684

  • Significantly Lower Infection Risk For ACL Grafts Pre-Soaked in Vancomycin Compared to Un-Soaked Grafts: A Systematic Review and Meta-analysis. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association Xiao, M. n., Sherman, S. L., Safran, M. R., Abrams, G. D. 2020

    Abstract

    To compare post-operative infection rates following ACL reconstruction performed with grafts pre-soaked in vancomycin versus those without vancomycin.A systematic review was performed using PRISMA guidelines. PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for therapeutic level I-III studies that compared outcomes of pre-soaking ACL grafts with vancomycin versus without vancomycin in human patients. Included graft types were tendon autografts or allografts, and studies documenting infection with a minimum follow-up of 30 days were included. Postoperative infection rates and knee-specific patient reported outcome scores were extracted from each study and compared between groups. Study methodological quality was analyzed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Coleman Methodology Score (MCMS). Infection rates and re-tear rates were pooled and weighted for meta-analysis using a random-effects model. All P values were reported with an alpha level of 0.05 set as significant.The initial search yielded 144 articles (44 duplicates, 100 screened, 29 full-text review). Ten articles (21,368 subjects [7,507 vancomycin and 13,861 no vancomycin], 67% males, mean age 29.5 + 1.5 years old) were included and analyzed. Eight of the 10 studies included only autografts, with 94.5% of grafts being hamstring autografts. Soaking grafts in vancomycin resulted in significantly fewer infections (0.013% vs 0.77%; OR 0.07 [0.03, 0.18], p < 0.001). Only two studies included patient reported outcomes, and both demonstrated no difference in International Knee Documentation Committee (IKDC) scores one year after surgery for patients with grafts pre-soaked in vancomycin compared to without vancomycin.Soaking ACL tendon grafts with vancomycin prior to implantation is associated with a nearly 15 times decrease in odds of infection compared to grafts not soaked in vancomycin. There were few studies that investigated patient reported outcomes and re-tear rates after soaking ACL grafts in vancomycin.

    View details for DOI 10.1016/j.arthro.2020.12.212

    View details for PubMedID 33359822

  • Soaking of Autologous Tendon Grafts in Vancomycin Before Implantation Does Not Lead to Tenocyte Cytotoxicity. The American journal of sports medicine Xiao, M. n., Leonardi, E. A., Sharpe, O. n., Sherman, S. L., Safran, M. R., Robinson, W. H., Abrams, G. D. 2020: 363546520951815

    Abstract

    Surgical site infections (SSIs) after anterior cruciate ligament (ACL) reconstruction procedures are an unfortunate complication. Soaking grafts in vancomycin before implantation has been reported to reduce the incidence of postoperative SSI after ACL reconstruction. There is potential for vancomycin to compromise graft integrity because of tenocyte toxicity.To examine the in vitro toxicity of varying doses of vancomycin on human tenocytes.Controlled laboratory study.Human patellar tenocytes were isolated and expanded in vitro. Tenocytes in culture were exposed to vancomycin at 5 different concentrations (400, 1600, 3200, 6400, and 12,800 μg/mL) and 3 time intervals (2, 6, and 24 hours). The control for all series was tenocyte exposure to only culture medium for each time interval. After treatment, a 10% Cell Counting Kit-8 solution in cellular growth medium was applied to the cells to examine cytotoxicity. A live/dead assay was used to assess tenocyte viability through fluorescence microscopy and flow cytometry. Results were analyzed statistically using multivariable logistic regression models with Tukey honest significant difference post hoc tests.Vancomycin did not cause significant changes in tenocyte viability after 2 and 6 hours of incubation at any concentration between 0 and 12,800 µg/mL. Incubation with vancomycin for 24 hours led to a significant decrease in cell viability at higher concentrations.Tenocytes derived from human patellar tendons exposed to relatively high concentrations of vancomycin for short periods of time do not demonstrate significant cell death and toxicity.Exposing tendons to vancomycin for a short period of time, such as before ACL reconstruction, is not likely to cause tenocyte toxicity because of vancomycin administration.

    View details for DOI 10.1177/0363546520951815

    View details for PubMedID 32898431

  • Cost minimization analysis of the treatment of olecranon fracture in elderly patients: a retrospective analysis CURRENT ORTHOPAEDIC PRACTICE Welch, J. M., Zhuang, T., Shapiro, L. M., Gardner, M., Xiao, M., Kamal, R. N. 2022; 33 (6): 559-564
  • Analysis of Website Accessibility and Content for All 92 Accredited Hand Surgery Fellowship Programs in the United States: An Update. Journal of hand surgery global online Cohen, S. A., Xiao, M., Curtin, C. M., Yao, J. 2022; 4 (5): 269-275

    Abstract

    Purpose: The internet is an important information source for hand surgery fellowship applicants. A previous analysis of hand fellowship websites in 2014 demonstrated they were often inaccessible and incomplete. Given the increased importance of virtual information, we performed an updated assessment of the accessibility and content of hand fellowship program websites.Methods: Websites of 92 accredited hand surgery fellowship programs were evaluated for the following: (1) accessibility; and (2) the presence of 13 fellow recruitment and 13 fellow education criteria, as defined in prior studies. We used Mann-Whitney U and Kruskal-Wallis tests to assess whether the geographic region, number of fellows, or affiliation with a top orthopedic hospital or medical school were associated with website content.Results: Functional website links that redirect to the appropriate fellowship program website are provided for 47 (51.1%) of 92 programs on the American Society for Surgery of the Hand fellowship directory. All missing websites were accessible via independent Google searches. Fellowship program websites contained an average of 13.9 ± 4.4 total criteria (range, 3-23). Of the 15 criteria examined in both 2014 and 2021, there were significant (P < .05) increases in the prevalences of 4: current fellow(s), salary, social media links, and operative experience.Conclusions: Despite a slight increase in accessibility since 2014, nearly half of hand surgery fellowship program websites remain inaccessible from the American Society for Surgery of the Hand directory. Program websites averaged approximately half of the criteria analyzed, with many websites failing to provide information deemed important by applicants.Clinical relevance: Our study provides an impetus for improving the accessibility and content of hand surgery fellowship websites. A website that incorporates criteria examined in this study can serve as an effective recruitment tool by providing consistent baseline information that may help applicants decide which programs align with personal values and future career goals.

    View details for DOI 10.1016/j.jhsg.2022.05.004

    View details for PubMedID 36157307

  • Increased Risk of ACL Injury for Female but Not Male Soccer Players on Artificial Turf Versus Natural Grass: A Systematic Review and Meta-Analysis. Orthopaedic journal of sports medicine Xiao, M., Lemos, J. L., Hwang, C. E., Sherman, S. L., Safran, M. R., Abrams, G. D. 2022; 10 (8): 23259671221114353

    Abstract

    Background: Both natural grass (NG) and artificial turf (AT) are popular playing surfaces for soccer. Biomechanical studies have found increased frictional forces on AT that may lead to anterior cruciate ligament (ACL) injury. The increased risk of ACL injury during soccer in female participants may amplify this effect.Purpose: To systematically review the literature for studies comparing ACL injury risk in soccer players on AT versus NG and to specifically determine whether there were differences in injury risk in male versus female players when considering the playing surface.Study Design: Systematic review; Level of evidence, 3.Methods: A systematic review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Three databases were searched for studies with evidence level 1 to 3 that compared the incidence of ACL injuries on AT versus NG in soccer players. Data recorded included study characteristics, sex, competition level, exposure setting (games or practices), turf type, and ACL injury information. Study methodological quality was analyzed using the methodological index for non-randomized studies (MINORS) score, and incidence rate ratios (IRRs) were calculated.Results: Included were 7 articles (3 studying professional soccer, 3 collegiate soccer, 1 youth-level soccer; 4 male cohorts, 2 female cohorts, and 1 male and female cohort; mean MINORS score, 20 ± 0.8). Pooled ACL injury IRRs demonstrated no significant differences in overall ACL injury risk when playing soccer on AT compared with NG (IRR = 0.57 [95% CI, 0.21-1.53]; P = .31). A significantly increased risk of ACL injury in games played on AT compared with NG was detected for female (IRR = 1.18 [95% CI, 1.05-1.31]; P = .004) but not for male players (IRR = 1.18 [95% CI, 0.97-1.42]; P = .09). Subgroup analyses showed no significant differences in injury risk for games (IRR = 1.07 [95% CI, 0.97-1.18]; P = .20) or practices (IRR = 0.21 [95% CI, 0.04-1.23]; P = .09).Conclusion: Findings indicated that female soccer players had a significantly higher risk of ACL injury when playing games on AT versus NG, whereas no significant difference was seen in male players. No differences were found for the combined male/female cohort or for soccer games or training sessions played on AT compared with NG.

    View details for DOI 10.1177/23259671221114353

    View details for PubMedID 35990873

  • Variations in Treatment and Costs for Distal Radius Fractures in Patients Over 55 Years of Age: A Population-Based Study JOURNAL OF HAND AND MICROSURGERY Shapiro, L. M., Xiao, M., Zhuang, T., Ruch, D. S., Richard, M. J., Kamal, R. N. 2022
  • Limited Biomechanical Evidence Behind Single Row Versus Double Row Repair of Subscapularis Tears: ASystematic Review. Arthroscopy, sports medicine, and rehabilitation Xiao, M., Cohen, S. A., Cheung, E. V., Sherman, S. L., Abrams, G. D., Freehill, M. T. 2022; 4 (3): e1193-e1201

    Abstract

    Purpose: To systematically review the literature for studies investigating the biomechanical properties of constructs used to repair isolated subscapularis tears in time zero human cadaveric studies.Methods: A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three electronic databases were searched for studies that reported on the construct technique and biomechanical outcomes for the repair of isolated subscapularis tears in human cadaveric specimens. Ultimate load, gap formation, stiffness, and failure mode were documented. Methodological quality was assessed using the Quality Appraisal for Cadaveric Studies (QUACS) scale.Results: Six articles qualified (104 shoulders [72 single-row, 26 double-row, 6 transosseous]; mean QUACS score 10.5 ± 1) and were analyzed. Studies varied in the number and type of anchors and construct technique (1-2 anchors single-row; 3-4 anchors double-row; bioabsorbable or titanium anchors) and suture(s) used (no. 2 FiberWire or FiberTape), subscapularis tear type (25%, 33%, 50%, or 100% tear), and whether a knotless or knotted fixation was used. In studies that created full-thickness, upper subscapularis tears (Fox-Romeo II/III or Lafosse II), no significant differences were seen in ultimate load, gap formation, and stiffness for knotted versus knotless single-row repair (2 studies) and single-row versus double-row repair (1 study). Double-row repair of complete subscapularis tears demonstrated higher ultimate load, stiffness, and lower gap formation in 1 study. Ultimate load differed between the studies and constructs (single-row: range, 244 N to 678 N; double-row: range 332 N to 508 N, transosseous: 453 N). Suture cutout was the most common mode of failure (59%).Conclusion: Because of the limited number of studies and varying study designs in examining the biomechanical properties of repair constructs used for subscapularis tears, there is inconclusive evidence to determine which construct type is superior for repairing subscapularis tears.Clinical Relevance: Results from biomechanical studies of clinically relevant subscapularis repair constructs are important to guide decision-making for choosing the optimal construct for patients with subscapularis tears.

    View details for DOI 10.1016/j.asmr.2022.01.009

    View details for PubMedID 35747639

  • Editorial Commentary: Soaking Anterior Cruciate Ligament Grafts in Vancomycin Solution Lowers Infection Rates Without Lowering Functional Outcomes. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association Xiao, M., Abrams, G. D., Editorial Board 2022; 38 (5): 1535-1536

    Abstract

    Soaking anterior cruciate ligament grafts in vancomycin solution is done by many surgeons. Research has indicated decreased infection rates and similar anterior cruciate ligament retear rates between grafts soaked in vancomycin solution before implantation versus those without. In addition, there has been basic science evidence for tenocyte survival and viability even when exposed to vancomycin solution. The next frontier, investigating the maturation of vancomycin-soaked grafts with advanced imaging, may cause some surgeons to reconsider the practice but should not stop it, based on the available literature.

    View details for DOI 10.1016/j.arthro.2021.11.022

    View details for PubMedID 35501018

  • How do orthopaedic surgery residency program websites feature diversity? An analysis of 187 orthopaedic surgery programs in the United States. Current orthopaedic practice Cohen, S. A., Xiao, M., Zhuang, T., Michaud, J., Wadhwa, H., Shapiro, L., Kamal, R. N. 2022; 33 (3): 258-263

    Abstract

    Background: The orthopaedic surgery residency program website represents a recruitment tool that can be used to demonstrate a program's commitment to diversity and inclusion to prospective applicants. The authors assessed how orthopaedic surgery residency programs demonstrated diversity and inclusion on their program websites and whether this varied based on National Institutes of Health (NIH) funding, top-40 medical school affiliation, university affiliation, program size, or geographic region.Methods: The authors evaluated 187 orthopaedic surgery residency program websites for the presence of 12 elements that represented program commitment to diversity and inclusion values, based on prior work and ACGME recommendations. Mann-Whitney U and Kruskal-Wallis tests were used to assess whether NIH funding and other program characteristics were associated with commitment to diversity and inclusion on affiliated residency websites.Results: Orthopaedic surgery residency websites included a mean of 4.9 ± 2.1 diversity and inclusion elements, with 21% (40/187) featuring a majority (7+) of elements. Top 40 NIH funded programs (5.4 ± 2.0) did not have significantly higher website diversity scores when compared with nontop-40 programs (4.8 ± 2.1) (P = 0.250). University-based or affiliated programs (5.2 ± 2.0) had higher diversity scores when compared with community-based programs (3.6 ± 2.2) (P = 0.003).Conclusions: Most orthopaedic surgery residency websites contained fewer than half of the diversity and inclusion elements studied, suggesting opportunities for further commitment to diversity and inclusion. Inclusion of diversity initiatives on program websites may attract more diverse applicants and help address gender and racial or ethnic disparities in orthopaedic surgery.Level of Evidence: Level V.

    View details for DOI 10.1097/bco.0000000000001101

    View details for PubMedID 35685001

  • How Is Scaphoid Malunion Defined: A Systematic Review. Hand (New York, N.Y.) Xiao, M., Welch, J. M., Cohen, S. A., Kamal, R. N., Shapiro, L. M. 2021: 15589447211038678

    Abstract

    BACKGROUND: Abnormal scaphoid alignment after fracture is used as an indication for fixation. Acceptable alignment after reduction and fixation of scaphoid fractures is not well defined. We systematically reviewed the literature to identify how scaphoid malunion is currently defined and by what parameters.METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Multiple databases were searched for studies published in the English language that reported on outcomes after scaphoid malunion and included measurements to define malunions. Radiographic scaphoid measurement parameters were collected. Clinical outcome measures recorded included grip strength, wrist range of motion, and patient-reported outcome measures. Study quality was analyzed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Descriptive summaries of the studies are presented.RESULTS: The initial search yielded 1600 articles. Ten articles (161 participants, 93% males, mean age = 28.3 + 6.3 years, mean MINORS score = 10.2 + 1.6) were included and analyzed. Scaphoid malunion was defined if the lateral intrascaphoid angle (LISA) was >45° (3 articles), LISA >35° (1 article), and height to length ratio >0.6 (3 articles). Four out of 5 studies found no significant associations between patient outcomes and degree of scaphoid malunion measured on imaging.CONCLUSIONS: There is a lack of consensus for defining scaphoid malunion on imaging and absence of correlation between findings on imaging and patient outcomes. Future studies defining scaphoid malunion should be appropriately powered, incorporate measures of intrarater and interrater reliabilities for all reported imaging measurements, and utilize validated patient-reported outcome measures to reflect that malunion is associated with inferior outcomes meaningful to patients.

    View details for DOI 10.1177/15589447211038678

    View details for PubMedID 34486427

  • Tendon-Derived Progenitor Cells With Multilineage Potential Are Present Within Human Patellar Tendon. Orthopaedic journal of sports medicine Leonardi, E. A., Xiao, M., Murray, I. R., Robinson, W. H., Abrams, G. D. 2021; 9 (8): 23259671211023452

    Abstract

    Background: Progenitor cells serve as a promising source of regenerative potential in a variety of tissue types yet remain underutilized in tendinopathy. Tendon-derived progenitor cells (TDPCs) have previously been isolated from hamstring tendon but only as part of a concomitant medical procedure. Determining the presence of TDPCs in patellar tendon may facilitate clinical utilization of these cells because of the relative accessibility of this location for tissue harvest.Purpose: To characterize TDPCs in human patellar tendon samples.Study Design: Descriptive laboratory study.Methods: Human patellar tendon samples were obtained during elective knee surgery. TDPCs were isolated and seeded at an optimal low cell density and subcultured to confluence for up to 2 passages. Flow cytometry was used to analyze for the expression of CD90+, CD105+, CD44+, and CD31-, CD34-, and CD45- markers. The multilineage differentiation potential of TDPCs was tested in vitro via adipogenic, osteogenic, and chondrogenic culture with subsequent cytochemical staining for Oil Red O, Alizarin Red, and Alcian Blue, respectively. Enzyme-linked immunosorbent assay was used to quantify the amount of adiponectin, alkaline phosphatase, and SRY-box transcription factor 9 secreted into cell culture supernatant for further confirmation of lineage differentiation. Results were analyzed statistically using the 2-tailed Student t test.Results: TDPCs demonstrated near-uniform expression of CD90, CD105, and CD44 with minimal expression of CD34, CD31, and CD45. Adipogenic, osteogenic, and chondrogenic differentiation of TDPCs was confirmed using qualitative analysis. The expression of adiponectin, alkaline phosphatase, and SRY-box transcription factor 9 were significantly increased in differentiated cells versus undifferentiated TDPCs (P < .05).Conclusion: TDPCs can be successfully isolated from human patellar tendon samples, and they exhibit characteristics of multipotent progenitor cells.Clinical Relevance: These data demonstrate the promise of patellar tendon tissue as a source of progenitor cells for use in biologic therapies for the treatment of tendinopathy.

    View details for DOI 10.1177/23259671211023452

    View details for PubMedID 34435068

  • Google Trends Analysis Shows Increasing Public Interest in Platelet-Rich Plasma Injections for Hip and Knee Osteoarthritis. The Journal of arthroplasty Cohen, S. A., Zhuang, T., Xiao, M., Michaud, J. B., Amanatullah, D. F., Kamal, R. N. 2021

    Abstract

    BACKGROUND: Osteoarthritis is a chronic musculoskeletal condition that frequently affects the hip and knee joints. Given the burden associated with surgical intervention for hip and knee osteoarthritis, patients continue to search for potential nonoperative treatments. One biologic therapy with mixed clinical and basic science evidence for treating osteoarthritis is platelet-rich plasma injections into the affected joint. We used the Google Trends tool to provide a quantitative analysis of national interest in platelet-rich plasma injections for hip and knee osteoarthritis.METHODS: Google Trends parameters were selected to obtain search data from January 2009 to December 2019. Various combinations of "arthritis," "osteoarthritis," "PRP," "platelet-rich plasma," "knee," and "hip" were entered into the Google Trends tool and trend analyses were performed.RESULTS: Three linear models were generated to display search volume trends in the United States for platelet-rich plasma and osteoarthritis, hip osteoarthritis, and knee osteoarthritis, respectively. All models showed increased Google queries as time progressed (P < .001), with R2 ranging from 0.837 to 0.940. Seasonal, income-related, and geographic variations in public interest in platelet-rich plasma for osteoarthritis were noted.CONCLUSION: Our results demonstrate a significant rise in Google queries related to platelet-rich plasma injections for osteoarthritis of the hip and knee since 2009. Surgeons treating hip and knee osteoarthritis patients can expect continued interest in platelet-rich plasma, despite inconclusive clinical and basic science data. Trends in public interest may inform patient counseling, shared decision-making, and directions for future clinical research.

    View details for DOI 10.1016/j.arth.2021.05.040

    View details for PubMedID 34172346

  • Arthroscopic Single and Double Row Repair of Isolated and Combined Subscapularis Tears Result in Similar Improvements in Outcomes: A Systematic Review. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association Xiao, M., Cohen, S. A., Cheung, E. V., Abrams, G. D., Freehill, M. T. 2021

    Abstract

    PURPOSE: To systematically review the literature to 1) describe arthroscopic subscapularis repair constructs and outcomes in patients with isolated and combined subscapularis tears and 2) compare outcomes following single and double row subscapularis repair in both of these settings.METHODS: A systematic review was performed using PRISMA guidelines. PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for Level I-IV evidence studies that investigated outcomes after arthroscopic subscapularis repair for the treatment of isolated subscapularis tears or subscapularis tears combined with posterosuperior rotator cuff tears in adult human patients. Data recorded included study demographics, repair construct, shoulder-specific outcome measures, and subscapularis re-tears. Study methodological quality was analyzed using the MINORS score. Heterogeneity and low levels of evidence precluded meta-analysis.RESULTS: The initial search yielded 811 articles (318 duplicates, 493 screened, 67 full-text review). Forty-three articles (2,406 shoulders, 57% males, mean age range 42 to 67.5 years, mean MINORS score 13.4 + 4.1) were included and analyzed. Articles reported on patients with isolated subscapularis tears (n = 15), combined tears (n = 17), or both (n = 11). The majority of subscapularis repairs utilized single-row constructs (89.4% of isolated tears, 88.9% of combined tears). All except for one study reporting on outcome measures found clinically significant improvements after subscapularis repair, and no clinically significant differences were detected in five studies comparing isolated to combined tears. Subscapularis re-tear rates ranged from 0% to 17% for isolated tears and 0% to 32% for combined subscapularis and posterosuperior rotator cuff tears. Outcomes and re-tear rates were similar in studies comparing single-row to double-row repair for isolated and combined subscapularis tears (p > 0.05 for all).CONCLUSION: Arthroscopic subscapularis repair resulted in significant improvements across all outcome measures, regardless if tears were isolated or combined or if repairs were single or double row.

    View details for DOI 10.1016/j.arthro.2021.05.032

    View details for PubMedID 34052379

  • Uvular Necrosis After Shoulder Surgery: A Report of Three Cases CUREUS Xiao, M., Kaufman, D., Abrams, G. D. 2021; 13 (3)
  • Using Google Trends Data to Track Healthcare Use for Hand Osteoarthritis. Cureus Cohen, S. A., Zhuang, T., Xiao, M., Michaud, J. B., Shapiro, L., Kamal, R. N. 2021; 13 (3): e13786

    Abstract

    Background Google Trends (GT) is a free tool that provides analysis of search traffic for specified terms entered into the Google search engine. In this study, we evaluate the association between public interest in hand osteoarthritis (OA) as determined by GT search volumes and healthcare usage related to hand OA. Methodology We compiled GT data from 2010 to 2017 for the following group of hand OA-related search terms: "hand osteoarthritis," "hand arthritis," "hand swelling," "hand stiffness," and "chronic hand pain." Claims associated with hand OA codes were obtained from an administrative database (14.8 million patients) using International Classification of Diseases codes from 2010 to 2017. We performed trend analysis using univariate linear regression of GT data and hand OA claims. A month-by-month analysis of variation from yearly GT means was conducted for hand OA-related search terms. Results There was increased public interest in hand OA-related search terms from January 2010 to December 2017. Univariate linear regression of GT data for hand OA-related search terms compared with hand OA claims demonstrated a significant positive correlation (p < 0.001, r = 0.707). Peak public interest in hand OA-related search terms was observed in July, May, and June. Conclusions This study demonstrates the ability of GT to track healthcare use related to hand OA. Our data also add to the evidence for monthly variations in public interest related to hand OA. Clinics and surgery centers can employ GT data to anticipate resource utilization by hand OA patients.

    View details for DOI 10.7759/cureus.13786

    View details for PubMedID 33842160

    View details for PubMedCentralID PMC8025802

  • Inflammatory Mechanisms in the Development of Osteoarthritis. Instructional course lectures Xiao, M., Sherman, S. L., Abrams, G. D. 2021; 70: 537-550

    Abstract

    Osteoarthritis was traditionally thought of as a noninflammatory disease, but improved molecular techniques have recognized a significant inflammatory component. An initial joint injury or biomechanical imbalance leads to local tissue damage and inflammation, which is propagated by the innate immune system. The production of damage-associated molecular patterns (DAMPs) results in the activation of immune-modulated mechanisms, leading to the production of catabolic factors that can damage native joint structures such as cartilage. DAMPs may originate from extracellular matrix degradation products, intracellular components of lysed cells, complement, or joint crystals-even plasma proteins can enter through an inflamed synovium and further perpetuate the inflammatory process. Therapeutic interventions have traditionally focused on symptom management; however, there is potential for pharmacologic modification of the disease process in osteoarthritis through novel anti-inflammatory agents.

    View details for PubMedID 33438934

  • Increased Lower Extremity Injury Risk Associated With Player Load and Distance in Collegiate Women's Soccer. Orthopaedic journal of sports medicine Xiao, M., Nguyen, J. N., Hwang, C. E., Abrams, G. D. 2021; 9 (10): 23259671211048248

    Abstract

    There is limited research regarding the impact of workload on injury risk specific to women's soccer. Wearable global positioning system (GPS) units can track workload metrics such as total distance traveled and player load during games and training sessions. These metrics can be useful in predicting injury risk.To examine the relationship between injury risk and player workload as collected from wearable GPS units in National Collegiate Athletic Association (NCAA) Division I women's soccer players.Case-control study; Level of evidence, 3.Lower extremity injury incidence and GPS workload data (player load, total distance, and high-speed distance) for 65 NCAA Division I women's soccer players were collected over 3 seasons. Accumulated 1-, 2-, 3-, and 4-week loads and acute-to-chronic workload ratios (ACWR) were classified into discrete ranges by z-scores. ACWR was calculated using rolling averages and exponentially weighted moving averages (EWMA) models. Binary logistic regression models were used to compare the 7:28 rolling average and EWMA ACWRs between injured and noninjured players for all GPS/accelerometer variables. The prior 1-, 2-, 3-, and 4-week accumulated loads for all GPS/accelerometer variables were compared between the injured and uninjured cohorts using 2-sample t tests.There were a total of 53 lower extremity injuries that resulted in lost time recorded (5.76/1000 hours "on-legs" exposure time; 34 noncontact and 19 contact injuries). The prior 2-week (7242 vs 6613 m/s2; P = .02), 3-week (10,533 vs 9718 m/s2; P = .02), and 4-week (13,819 vs 12,892 m/s2; P = .04) accumulated player loads and 2-week (62.40 vs 57.25 km; P = .04), 3-week (90.97 vs 84.10 km; P = .03), and 4-week (119.31 vs 111.38 km; P = .05) accumulated total distances were significantly higher for injured players compared with noninjured players during the same time frames. There were no significant differences in player load, total distance, or high-speed distance ACWR between injured and noninjured players for both the rolling averages and EWMA calculations.Higher accumulated player load and total distance, but not ACWR, were associated with injury in women's soccer players.

    View details for DOI 10.1177/23259671211048248

    View details for PubMedID 34722786

    View details for PubMedCentralID PMC8552401

  • Is Frailty Associated with Adverse Outcomes After Orthopaedic Surgery?: A Systematic Review and Assessment of Definitions. JBJS reviews Lemos, J. L., Welch, J. M., Xiao, M., Shapiro, L. M., Adeli, E., Kamal, R. N. 1800; 9 (12)

    Abstract

    BACKGROUND: There is increasing evidence supporting the association between frailty and adverse outcomes after surgery. There is, however, no consensus on how frailty should be assessed and used to inform treatment. In this review, we aimed to synthesize the current literature on the use of frailty as a predictor of adverse outcomes following orthopaedic surgery by (1) identifying the frailty instruments used and (2) evaluating the strength of the association between frailty and adverse outcomes after orthopaedic surgery.METHODS: A systematic review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched to identify articles that reported on outcomes after orthopaedic surgery within frail populations. Only studies that defined frail patients using a frailty instrument were included. The methodological quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). Study demographic information, frailty instrument information (e.g., number of items, domains included), and clinical outcome measures (including mortality, readmissions, and length of stay) were collected and reported.RESULTS: The initial search yielded 630 articles. Of these, 177 articles underwent full-text review; 82 articles were ultimately included and analyzed. The modified frailty index (mFI) was the most commonly used frailty instrument (38% of the studies used the mFI-11 [11-item mFI], and 24% of the studies used the mFI-5 [5-item mFI]), although a large variety of instruments were used (24 different instruments identified). Total joint arthroplasty (22%), hip fracture management (17%), and adult spinal deformity management (15%) were the most frequently studied procedures. Complications (71%) and mortality (51%) were the most frequently reported outcomes; 17% of studies reported on a functional outcome.CONCLUSIONS: There is no consensus on the best approach to defining frailty among orthopaedic surgery patients, although instruments based on the accumulation-of-deficits model (such as the mFI) were the most common. Frailty was highly associated with adverse outcomes, but the majority of the studies were retrospective and did not identify frailty prospectively in a prediction model. Although many outcomes were described (complications and mortality being the most common), there was a considerable amount of heterogeneity in measurement strategy and subsequent strength of association. Future investigations evaluating the association between frailty and orthopaedic surgical outcomes should focus on prospective study designs, long-term outcomes, and assessments of patient-reported outcomes and/or functional recovery scores.CLINICAL RELEVANCE: Preoperatively identifying high-risk orthopaedic surgery patients through frailty instruments has the potential to improve patient outcomes. Frailty screenings can create opportunities for targeted intervention efforts and guide patient-provider decision-making.

    View details for DOI 10.2106/JBJS.RVW.21.00065

    View details for PubMedID 34936580

  • Outcomes After Resection Arthroplasty Versus Permanent Antibiotic Spacer for Salvage Treatment of Shoulder Periprosthetic Joint Infections: A Systematic Review and Meta-Analysis. Journal of shoulder and elbow surgery Xiao, M., Money, A., Pullen, W. M., Cheung, E. V., Abrams, G. D., Freehill, M. T. 2021

    Abstract

    Although revision to new components is favored following shoulder periprosthetic joint infections (PJI), implant exchange is not always feasible. In certain cases, definitive treatment may be retainment of an antibiotic spacer or resection arthroplasty. The purpose of this investigation was to systematically review the literature for studies reporting on outcomes after resection arthroplasty or permanent antibiotic spacer for salvage treatment of shoulder PJIs.A systematic review was performed using PRISMA guidelines. PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for Level I-IV studies that reported on the final treatment of periprosthetic shoulder infections using resection arthroplasty or a permanent antibiotic spacer. Data recorded included study demographics, causative infectious organism, shoulder-specific range of motion and outcome measures, and infection eradication rate. Study methodological quality was analyzed using the Methodological Index for Non-Randomized Studies (MINORS) score. Forest plots of proportions and meta-analyses of single means were generated for infection eradication rates and outcomes, respectively. Heterogeneity was quantified using the I2 statistic. A P value of 0.05 was set as significant.The initial search yielded 635 articles (211 duplicates, 424 screened, 57 full-text review). Twenty-three articles (126 resection arthroplasty and 177 retained antibiotic spacer patients, 51% females, mean age range 37 to 78.5 years, mean MINORS score 9.6 + 0.7) were included and analyzed. The pooled infection eradication rate was 82% [72% - 89%] following resection arthroplasty and 85% [79% - 90%] after permanent antibiotic spacer. The pooled mean forward flexion (71.5˚ versus 48.7˚; p < 0.001) and mean American Shoulder and Elbow Surgeons (ASES) score (53.5 versus 31.0; p < 0.001) was significantly higher for patients treated with permanent antibiotic spacer compared to resection arthroplasty. No significant differences were found for mean external rotation (13.5˚ versus 20.5˚; p = 0.07), abduction (58.2˚ versus 50.3˚; p = 0.27), or visual analog scale (VAS) pain (3.7 versus 3.4; p = 0.24) between groups. There was a statistically significant, but not clinically significant, difference in mean Constant score between permanent antibiotic spacer and resection arthroplasty patients (33.6 versus 30.0; p < 0.001).When implant exchange following shoulder PJI is not feasible, permanent antibiotic spacers and resection arthroplasty are both salvage procedures which provide similar rates of infection eradication. Though both can decrease pain levels, permanent antibiotic spacer may result in better functional outcomes compared to resection arthroplasty.

    View details for DOI 10.1016/j.jse.2021.10.016

    View details for PubMedID 34774777

  • Preoperative Fatty Infiltration of the Teres Minor Negatively Affects Postoperative Outcomes in Patients With Rotator Cuff Pathology. Orthopaedic journal of sports medicine Sarkissian, E. J., Xiao, M., Abrams, G. D. 2020; 8 (10): 2325967120960107

    Abstract

    Background: The teres minor is a critical component of the rotator cuff and serves as one of the few external rotators of the humerus. Information is lacking regarding the effect of teres minor atrophy in isolation and in the setting of concomitant full-thickness rotator cuff tears on outcomes in patients undergoing rotator cuff surgery.Purpose: To investigate the effect of preoperative teres minor fatty infiltration on postoperative clinical outcomes in patients with and without full-thickness rotator cuff pathology.Study Design: Cohort study; Level of evidence, 3.Methods: A retrospective review of patients undergoing primary arthroscopic shoulder surgery between 2014 and 2016 was performed. Preoperative magnetic resonance imaging was used to determine fatty infiltration for each rotator cuff muscle using the modified Goutallier classification. American Shoulder and Elbow Surgeons (ASES) as well as the shortened version of Disabilities of the Arm, Shoulder and Hand (QuickDASH) scores were obtained preoperatively and during follow-up. Exclusion criteria included prior surgery on the ipsilateral shoulder or a diagnosis of inflammatory arthropathy. For analysis, patients were dichotomized to grade 0 or grade 1-4 atrophy of the teres minor as well as to full-thickness or partial-thickness rotator cuff pathology.Results: A total of 36 of 47 (76.6%) patients (mean age, 63 years; range, 45-76 years) were available for postoperative follow-up at a mean of 40 months (range, 30-48 months). Postoperative ASES score was significantly higher and QuickDASH score was significantly lower among all patients in the grade 0 group compared with the grade 1-4 group. Postoperative ASES and QuickDASH scores were not significantly different in patients with partial-thickness rotator cuff tears at any time point. However, the postoperative ASES score was significantly higher and QuickDASH score was significantly lower in the grade 0 versus grade 1-4 group for patients with full-thickness rotator cuff pathology.Conclusion: Preoperative teres minor atrophy in patients undergoing surgery for rotator cuff pathology may impair postoperative clinical outcomes, especially in patients with full-thickness tears.

    View details for DOI 10.1177/2325967120960107

    View details for PubMedID 33195718

  • Administrative Databases Utilized for Sports Medicine Research Demonstrate Significant Differences in Underlying Patient Demographics and Resulting Surgical Trends. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association Xiao, M. n., Donahue, J. n., Safran, M. R., Sherman, S. L., Abrams, G. D. 2020

    Abstract

    To discern differences between the PearlDiver and MarketScan databases with regards to patient demographics, costs, re-operations, and complication rates for isolated meniscectomy.We queried the PearlDiver Humana Patient Records Database and the IBM® MarketScan® Commercial Claims and Encounters database for all patients who had record of meniscectomy denoted by CPT-29880 or CPT-29881 codes between January 1, 2007 and December 31, 2016. Those that had any other knee procedure at the same time as the meniscectomy were excluded, and the first instance of isolated meniscectomy was recorded. Patient demographics, Charlson Comorbidity Index (CCI), reoperations, 30- and 90-day complication rates, and costs were collected from both databases. Pearson's χ2 test with Yate's continuity correction and the student t-test were used to compare the two databases, and an alpha value of 0.05 was set as significant.We identified 441,147 patients with isolated meniscectomy from the MarketScan database (0.36% of total database), approximately 10 times the number of patients (n = 49,924; 0.20% of total database) identified from PearlDiver. The PearlDiver population was significantly older (median age: 65-69) than the MarketScan cohort, where all patients were younger than 65 (median age: 52; p < 0.001). Average CCI was significantly lower for MarketScan (0.172, SD: 0.546) compared to PearlDiver (1.43, SD: 2.05; p < 0.001), even when restricting the PearlDiver cohort to patients under 65 (1.02, SD: 1.74; p < 0.001). The PearlDiver < 65 sub-cohort also had increased 30- (RR: 1.53 (1.40-1.67)) and 90-day (RR: 1.56 (1.47-1.66)) post-operative complications compared to MarketScan. Overall, laterality coding was more prevalent in the PearlDiver database.For those undergoing isolated meniscectomy, the MarketScan database comprised an overall larger and younger cohort of patients with fewer comorbidities, even when examining only subjects under 65 years of age.Level III, retrospective comparative study.

    View details for DOI 10.1016/j.arthro.2020.09.013

    View details for PubMedID 32966865

  • Exogenous micro-RNA and antagomir modulate osteogenic gene expression in tenocytes EXPERIMENTAL CELL RESEARCH Xiao, M., Iglinski-Benjamin, K. C., Sharpe, O., Robinson, W. H., Abrams, G. D. 2019; 378 (2): 119–23
  • Increased reoperation rates among patients undergoing shoulder arthroscopy with concomitant biceps tenodesis. JSES open access Xiao, M. n., Abrams, G. D. 2019; 3 (4): 344–49

    Abstract

    The purpose of this study was to determine whether patients undergoing any shoulder arthroscopic procedure with concomitant biceps tenodesis have higher reoperation and complication rates vs. patients undergoing shoulder arthroscopy without concomitant biceps tenodesis.A large database was queried for patients undergoing shoulder arthroscopy, identified by Current Procedural Terminology code. Only records indicating the laterality of the procedure were included. Patients were divided into 3 cohorts: arthroscopic shoulder surgery without concomitant biceps tenodesis (group 1), surgery with arthroscopic biceps tenodesis (group 2), and surgery with open biceps tenodesis (group 3). Reoperations on the same shoulder, as well as medical or surgical complications (by International Classification of Diseases, Ninth Revision code) during the 30-day postoperative period, were determined. Multivariate logistic regression was used to control for differences in age, sex, and Charlson Comorbidity Index between groups.We identified 62,461 patients (54.3% male patients) in the database who underwent shoulder arthroscopy, with 51,773 patients in group 1, 7134 patients in group 2, and 3554 patients in group 3. Overall, 3134 patients (5.0%) underwent a shoulder arthroscopy reoperation. With adjustment for age, sex, and Charlson Comorbidity Index, the biceps intervention groups demonstrated a significantly higher overall reoperation rate (odds ratio, 1.3 [95% confidence interval, 1.2-1.5]; P < .001). Patients undergoing biceps tenodesis had a lower adjusted overall 30-day complication rate vs. those not undergoing tenodesis (odds ratio, 0.82 [95% confidence interval, 0.79-0.86]; P < .001).Reoperation rates were significantly higher in patients undergoing shoulder arthroscopy with biceps tenodesis than in patients undergoing shoulder arthroscopy without biceps tenodesis. Both the arthroscopic and open tenodesis groups had significantly lower complication rates.

    View details for DOI 10.1016/j.jses.2019.08.002

    View details for PubMedID 31891037

    View details for PubMedCentralID PMC6928255

  • Increased Prevalence of Concomitant Psychiatric Diagnoses Among Patients Undergoing Hip Arthroscopic Surgery. Orthopaedic journal of sports medicine Iglinski-Benjamin, K. C., Xiao, M., Safran, M. R., Abrams, G. D. 2019; 7 (1): 2325967118822451

    Abstract

    Active patients with musculoskeletal pain are not immune to psychological or psychiatric disease. Observations suggest that patients undergoing hip arthroscopic surgery may have an increased prevalence of comorbid psychiatric conditions.Patients undergoing hip arthroscopic surgery have an increased prevalence of concomitant psychiatric diagnoses compared with the general population as well as those undergoing anterior cruciate ligament (ACL) reconstruction.Case-control study; Level of evidence, 3.A retrospective review of a medical claims database spanning from 2007 to 2016 was utilized to identify patients with a Current Procedural Terminology (CPT) code indicating that they had undergone hip arthroscopic surgery. This group was then dichotomized to those with or without an International Classification of Diseases, 9th Revision (ICD-9) and 10th Revision (ICD-10) diagnosis code indicating a psychological or psychiatric condition at any time before hip arthroscopic surgery or up to 2 years after hip arthrscopic surgery. As a control, ICD-9 and ICD-10 diagnosis codes for psychological or psychiatric conditions were determined in patients without a CPT code for hip arthroscopic surgery (general population) as well as for 2 surgical groups: those undergoing ACL reconstruction and those undergoing shoulder stabilization surgery. Prevalence was determined in all groups and compared using chi-square analysis.There were 22,676,069 patients in the database, with 2428 undergoing hip arthroscopic surgery. Those undergoing hip arthroscopic surgery had a 3-fold increased prevalence of concomitant psychiatric diagnoses compared with the general population (52% vs 17%, respectively; P < .0001). There was a significant difference in the prevalence of psychiatric diagnoses in the hip arthroscopic surgery group between male and female patients (46% vs 56%, respectively; P = .0061), with depression and anxiety being the 2 most common comorbid conditions. Those undergoing hip arthroscopic surgery also had a significantly increased prevalence of concomitant psychiatric diagnoses versus those undergoing ACL reconstruction (52% vs 28%, respectively; P < .0001) as well as those undergoing shoulder stabilization surgery (52% vs 42%, respectively; P < .0001).Patients undergoing hip arthroscopic surgery had an increased prevalence of comorbid psychiatric conditions compared with the general population as well as those undergoing ACL reconstruction or shoulder stabilization surgery. Depression and anxiety were the most prevalent concomitant psychiatric diagnoses.

    View details for DOI 10.1177/2325967118822451

    View details for PubMedID 30719482

    View details for PubMedCentralID PMC6348513

  • Design and synthesis of new piperidone grafted acetylcholinesterase inhibitors BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Basiri, A., Xiao, M., McCarthy, A., Dutta, D., Byrareddy, S. N., Conda-Sheridan, M. 2017; 27 (2): 228–31

    Abstract

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting 35million people worldwide. A common strategy to improve the well-being of AD patients consists on the inhibition of acetylcholinesterase with the concomitant increase of the neurotransmitter acetylcholine at cholinergic synapses. Two series of unreported N-benzylpiperidines 5(a-h) and thiazolopyrimidines 9(a-q) molecules were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities. Among the newly synthesized compounds, 5h, 9h, 9j, and 9p displayed higher AChE enzyme inhibitory activities than the standard drug, galantamine, with IC50 values of 0.83, 0.98, and 0.73μM, respectively. Cytotoxicity studies of 5h, 9h, 9j, 9n and 9p on human neuroblastoma cells SH-SY5Y, showed no toxicity up to 40μM concentration. Molecular docking simulations of the active compounds 5h and 9p disclosed the crucial role of π-π-stacking in their binding interaction to the active site AChE enzyme. The presented compounds have potential as AChE inhibitors and potential AD drugs.

    View details for DOI 10.1016/j.bmcl.2016.11.065

    View details for Web of Science ID 000392558500022

    View details for PubMedID 27914796

    View details for PubMedCentralID PMC5518470