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

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

Nutritionist Referral Modestly Improves Weight Loss and Increases Surgery Rate in Obese Patients Seeking Total Joint Arthroplasty.

Background: Obesity is associated with increased complications after total joint arthroplasty (TJA), leading some surgeons to recommend nutrition counseling and weight loss. We aim to evaluate the effect of preoperative nutritionist referral on weight loss and likelihood of surgery in obese patients seeking primary TJA. Methods: A retrospective cohort of patients seeking primary TJA who were referred to a licensed nutritionist for weight loss was matched by age, sex, and body mass index (BMI) to an unreferred control group. BMI change was compared between groups up to 1 year of follow-up. Differences were determined using 2-tailed t-tests and chi-squared tests with a significance cutoff of P < .05. Results: A total of 274 referred patients and 174 controls were included in our analysis. Patients who were referred to a nutritionist achieved significantly greater average BMI change (-1.5 kg/m2) than controls (-0.8 kg/m2) by 6 months after first contact (P = .01) although significance was lost at 1 year after first contact (P = .21). Thirty-eight percent of referred patients went on to TJA compared with 28% of controls (P < .01). Conclusions: Referral to a licensed nutritionist modestly improves early weight loss and is associated with a higher rate of surgery in obese patients seeking primary TJA.

Limiting the Surveillance Period to 90 Days Misses a Large Portion of Infections in the First Year After Total Hip and Knee Arthroplasty.

Background: In 2013, the Centers for Disease Control and Prevention reduced the periprosthetic joint infection (PJI) surveillance period from 1 year to 90 days for total hip (THA) and knee arthroplasty (TKA). Our aim was to determine how the reduced surveillance window impacts capture of PJIs. Material and methods: Primary and revision THA and TKA cases were retrospectively identified in a statewide registry from October 1, 2015, to September 30, 2018. Infections were defined using the Periprosthetic Joint/Wound Infection measure (Centers for Medicare and Medicaid Services). We compared the cumulative incidence of infected primary and revision THA (pTHA/rTHA) and TKA (pTKA/rTKA) at 0-90 days and 91-365 days postoperatively. Results: A total of 136,491 patients were included, 59.59% female, mean age 65.8 years, and mean body mass index 32.3 kg/m2. The overall rate of PJI diagnosed by 1 year was 1.33%. The percent of infections diagnosed between 0-90 days and 91-365 days were pTHA 76.78% and 23.22%, rTHA 74.12% and 25.88%, pTKA 57.67% and 42.33%, and rTKA 53.78% and 46.22%, respectively. More infections were diagnosed after 90 days in pTKA than in pTHA and in rTKA than in rTHA (P < .0001). There was a higher risk of infection throughout the year when comparing rTKA to rTHA (P = .0374) but not when comparing pTKA to pTHA (P = .0518). Conclusion: A substantial portion of infections are missed by the 90-day surveillance period. More infections are missed after TKA than after THA. Extension of the surveillance period would allow for identification of opportunities for quality improvement.

Coracoid morphology is not associated with subscapularis tears.

BACKGROUND: The observation of the roller-wringer effect fueled the idea that coracoid morphology is related to subscapularis pathology. We aimed to examine this relationship, specifically focusing on how the coracohumeral distance (CHD) and 2 new metrics of coracoid morphology relate to subscapularis tears. METHODS: In this retrospective study, we identified consecutive patients 45 years or older who underwent shoulder arthroscopy for any indication. We blindly reviewed preoperative magnetic resonance imaging studies of each patient, measuring the CHD, lateral extent (LE), and caudal extent (CE) of the coracoid process. Patients' subscapularis condition was assessed via operative reports; stratified according to Lafosse grade criteria; and compared for differences in the CHD, LE, and CE by 1-way analysis of variance and 2-tailed t tests. RESULTS: The study included 201 patients. Of these, 112 had no evidence of subscapularis injury, whereas Lafosse grade I injuries were identified in 52 patients; grade II, in 19; and grades III-V, in 18. The CHD, LE, and CE were not correlated with subscapularis injury (CHD, P = .36; LE, P = .36; and CE, P = .13). CONCLUSIONS: We found no correlation between subscapularis injury and the CHD, LE, and CE. These findings support the idea that coracoid morphology may not be a cause of subscapularis pathology and suggest that coracoplasty may not be necessary prophylactically or as part of subscapularis repair.

Targeting ALK in pediatric RMS does not induce antitumor activity in vivo.

PURPOSE: The anaplastic lymphoma kinase (ALK) has been demonstrated to be a valid clinical target in diseases such as anaplastic large cell lymphoma and non-small cell lung cancer. Recent studies have indicated that ALK is overexpressed in pediatric rhabdomyosarcoma (RMS) and hence we hypothesized that this kinase may be a suitable candidate for therapeutic intervention in this tumor. METHODS: We evaluated the expression of ALK in a panel of pediatric RMS cell lines and patient-derived xenografts (PDX), and sensitivity to ALK inhibitors was assessed both in vitro and in vivo. RESULTS: Essentially, all RMS lines were sensitive to crizotinib, NVP-TAE684 or LDK-378 in vitro, and molecular analyses demonstrated inhibition of RMS cell proliferation following siRNA-mediated reduction of ALK expression. However, in vivo PDX studies using ALK kinase inhibitors demonstrated no antitumor activity when used as single agents or when combined with standard of care therapy (vincristine, actinomycin D and cyclophosphamide). More alarmingly, however, crizotinib actually accelerated the growth of these tumors in vivo. CONCLUSIONS: While ALK appears to be a relevant target in RMS in vitro, targeting this kinase in vivo yields no therapeutic efficacy, warranting extreme caution when considering the use of these agents in pediatric RMS patients.

Repair of critical sized cranial defects with BMP9-transduced calvarial cells delivered in a thermoresponsive scaffold.

Large skeletal defects caused by trauma, congenital malformations, and post-oncologic resections of the calvarium present major challenges to the reconstructive surgeon. We previously identified BMP-9 as the most osteogenic BMP in vitro and in vivo. Here we sought to investigate the bone regenerative capacity of murine-derived calvarial mesenchymal progenitor cells (iCALs) transduced by BMP-9 in the context of healing critical-sized calvarial defects. To accomplish this, the transduced cells were delivered to the defect site within a thermoresponsive biodegradable scaffold consisting of poly(polyethylene glycol citrate-co-N-isopropylacrylamide mixed with gelatin (PPCN-g). A total of three treatment arms were evaluated: PPCN-g alone, PPCN-g seeded with iCALs expressing GFP, and PPCN-g seeded with iCALs expressing BMP-9. Defects treated only with PPCN-g scaffold did not statistically change in size when evaluated at eight weeks postoperatively (p = 0.72). Conversely, both animal groups treated with iCALs showed significant reductions in defect size after 12 weeks of follow-up (BMP9-treated: p = 0.0025; GFP-treated: p = 0.0042). However, H&E and trichrome staining revealed more complete osseointegration and mature bone formation only in the BMP9-treated group. These results suggest that BMP9-transduced iCALs seeded in a PPCN-g thermoresponsive scaffold is capable of inducing bone formation in vivo and is an effective means of creating tissue engineered bone for critical sized defects.

Stem cells, growth factors and scaffolds in craniofacial regenerative medicine.

Current reconstructive approaches to large craniofacial skeletal defects are often complicated and challenging. Critical-sized defects are unable to heal via natural regenerative processes and require surgical intervention, traditionally involving autologous bone (mainly in the form of nonvascularized grafts) or alloplasts. Autologous bone grafts remain the gold standard of care in spite of the associated risk of donor site morbidity. Tissue engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal defects. This strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials, osteoblastic stem cells, as well as osteoinductive growth factors and small molecules. One of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone regeneration. These properties include osteoconduction, osetoinduction, biocompatibility, biodegradability, vascularization, and progenitor cell retention. This review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.

Wnt and BMP Signaling Crosstalk in Regulating Dental Stem Cells: Implications in Dental Tissue Engineering.

Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

Multifaceted signaling regulators of chondrogenesis: Implications in cartilage regeneration and tissue engineering.

Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature. Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue. Here, we review the current understanding of the most important biological regulators of chondrogenesis and their interactions, to provide insight into potential applications for cartilage tissue engineering. These include various signaling pathways, including: fibroblast growth factors (FGFs), transforming growth factor ß (TGF-ß)/bone morphogenic proteins (BMPs), Wnt/ß-catenin, Hedgehog, Notch, hypoxia, and angiogenic signaling pathways. Transcriptional and epigenetic regulation of chondrogenesis will also be discussed. Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering.