Industry Payments to Foot and Ankle-Trained Orthopedic Surgeons: An Analysis of the Open Payments Database From 2014 to 2019.

Introduction The authors examined if the transparency in industry payments to foot and ankle-trained orthopedic surgeons resulted in the following changes to the (1) median general payments to surgeons, (2) trend in median payments to surgeons across all subcategory payments, and (3) trend in median payments to surgeons in 11 regions of the United States. Methods A retrospective review of the Centers for Medicare and Medicaid Services (CMS) and Open Payments Database (OPD) was performed to identify all industry payments made by drug and medical device companies to orthopedic surgeons (N = 3,835) between January 1, 2014, and December 31, 2019. Descriptive statistics were calculated, and trend analyses in annual payments, number of payments to surgeons per year, payment subtypes, and regional distributions were analyzed. Results A total of 53,280 payments totaling $53,454,850.56 were made to orthopedic foot and ankle surgeons between 2014 and 2019. Mean and median payments were $1,003.28 and $60.19, respectively. Statistically significant differences in mean payment amounts were observed by year (p = 0.001) with a highly statistically significant, strong increase in the number of payments made over the six-year period (r = 0.97, p < 0.001). The greatest increases in median individual payments were observed for gifts (277.1%; r = 0.18, p = 0.05), education (250.6%; r = 0.17, p < 0.001), and royalties and licensing (72.1%; r = 0.05, p = 0.04). Statistically significant increasing trends in median payments over time were observed for the Northeast (p < 0.001) and South regions (p < 0.001). Discussion The results of this study demonstrate the increase in payments made across the six-year time period. The study demonstrates that there is a shift in the type of payments from speaker fees, entertainment, and lodging to education, gifts, honoraria, royalties, and consulting. Conclusion Since the OPD release, no significant decrease was identified in the financial relationship between foot and ankle surgeons and the industry; rather, an increase was observed. This increase in education, royalties, and consulting shows that more foot and ankle surgeons are getting involved in the industry, contrary to expectations. The partnership between industry and physicians can help to improve innovation and bring new ideas to the future of orthopedics.

Risk Factors for Unexpected Admission Following Lumbar Spine Laminectomy: A National Database Study.

Introduction Laminectomy is one of the most common orthopedic spine surgeries performed in the United States. Compared to other spine operations such as fusions, laminectomies in isolation are of lower morbidity. However, complications may arise that result in readmission to an inpatient healthcare facility. The purpose of this study is to identify the demographics and risk factors associated with unplanned 30-day readmission following a laminectomy. Methods The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for patients who underwent a laminectomy procedure from 2015 to 2019 using CPT code 63030. This query yielded 61,708 cases. Demographic, lifestyle, comorbidity, and peri-operative factors were recorded. Independent samples Student's t-tests, chi-squared, and, where appropriate, Fisher's exact tests were used in univariate analyses to identify demographic, lifestyle, and peri-operative variables related to 30-day readmission following a laminectomy procedure. Multivariate logistic regression modeling was subsequently performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported. Results Of the 61,708 patients included in our sample, 2,359 were readmitted within 30 days of surgery, corresponding to a readmission rate of 3.82%. Results of the univariate analysis revealed statistically significant relationships between readmission status and the following patient variables: patient age, sex, BMI, ASA classification, race, bleeding disorder, chronic obstructive pulmonary disease (COPD), diabetes, hypertension, congestive heart failure (CHF), chronic steroid use, total operative time, and tobacco use (p < 0.05). Multivariate logistic regression modeling confirmed that the following patient variables were associated with statistically significantly increased odds of readmission: age greater than 65 (p < 0.05), female sex (p = 0.013), bleeding disorder (p = 0.011), diabetes (p = 0.006), current smoker (p = 0.010), COPD (p < 0.001), steroid use (p = 0.006), ASA Class II or above (p < 0.05), and total operative time (p < 0.001). Conclusion Unplanned 30-day readmission after laminectomy is infrequent. However, increasing age, female sex, steroid use, current smokers, bleeding disorders, diabetes, COPD, CHF, a higher ASA classification, and longer operative times are independent risk factors for readmission following laminectomy.

Industry Payments to Orthopedic Surgeons Among All Subspecialties: An Analysis of the Open Payments Database From 2014 to 2019.

Introduction Since the passage of the Physician Payments Sunshine Act in 2010, the Centers for Medicare and Medicaid Services (CMS) started the National Physician Payment Transparency Program and Open Payments Database (OPD), which allowed for public access to financial disclosures between physicians and industry. Although orthopedic surgeons receive the highest average payments when compared to other specialties, there has been limited data evaluating these payments among the different orthopedic subspecialties. The purpose of this study was to analyze all industry payments made across all subspecialties among orthopedic surgeons. Methods A retrospective review of the CMS OPD was performed to identify all industry payments made by drug and medical device companies to orthopedic surgeons (N = 28,475) between January 1, 2014, and December 31, 2019. Descriptive statistics were calculated for the number, individual value, and total value of industry payments, stratified by payment type and orthopedic subspecialty. Results A total of 1,048,573 payments (approximately $1.6 billion) were made to orthopedic surgeons between 2014 and 2019. The average orthopedic surgeon received 6.14 payments per year (SD = 29.39), with a mean individual payment amount of $1,542.32. Royalties or licensing comprised the greatest proportion of open payments, followed by consulting fees. Adult reconstruction (M = $225,131.10) and spine (M = $197,404.74) received significantly greater total payments when compared to all other subspecialties (all p-values ≤ 0.001). Differences in total payments made to trauma (M = $73,789.65), sports medicine (M = $60,988.09), foot and ankle (M = $45,007.45), pediatric orthopaedics (M = $35,898.54), general orthopaedics (M = $28,405.81), and hand (M = $14,027.76) were all found to be statistically equivalent (all p--values > 0.20). Discussion Increased collaboration between physicians and industry has resulted in the rapid advancement of innovation that can have sizeable financial implications among orthopedic surgeons. There exists significant heterogeneity in open payments made to orthopedic surgeons when stratified by subspecialty. Adult reconstructive and spine surgeons were the most compensated whereas hand and general orthopaedic surgeons received the least.

A new monoclonal antibody DAG-6F4 against human alpha-dystroglycan reveals reduced core protein in some, but not all, dystroglycanopathy patients.

We generated a novel monoclonal antibody, DAG-6F4, against alpha-dystroglycan which immunolabels the sarcolemma in human muscle biopsies. Its seven amino-acid epitope, PNQRPEL, was identified using phage-displayed peptides and is located immediately after the highly-glycosylated mucin domain of alpha-dystroglycan. On Western blots of recombinant alpha-dystroglycan, epitope accessibility was reduced, but not entirely prevented, by glycosylation. DAG-6F4 immunolabelling was markedly reduced in muscle biopsies from Duchenne muscular dystrophy patients consistent with disruption of the dystroglycan complex. In a range of dystroglycanopathy patients with reduced/altered glycosylation, staining by DAG-6F4 was often less reduced than staining by IIH6 (antibody against the glycan epitope added by LARGE and commonly used to identify glycosylated alpha-dystroglycan). Whereas IIH6 was reduced in all patients, DAG-6F4 was hardly changed in a LARGE patient, less reduced than IIH6 in limb-girdle muscular dystrophy type 2I, but as reduced as IIH6 in some congenital muscular dystrophy patients. Although absence of the LARGE-dependent laminin-binding site appears not to affect alpha-dystroglycan stability at the sarcolemma, the results suggest that further reduction in aDG glycosylation may reduce its stability. These studies suggest that DAG-6F4 may be a useful addition to the antibody repertoire for evaluating the dystroglycan complex in neuromuscular disorders.

Bone marrow-derived mesenchymal stem cells become antiangiogenic when chondrogenically or osteogenically differentiated: implications for bone and cartilage tissue engineering.

Osteochondral tissue repair requires formation of vascularized bone and avascular cartilage. Mesenchymal stem cells stimulate angiogenesis both in vitro and in vivo but it is not known if these proangiogenic properties change as a result of chondrogenic or osteogenic differentiation. We investigated the angiogenic/antiangiogenic properties of equine bone marrow-derived mesenchymal stem cells (eBMSCs) before and after differentiation in vitro. Conditioned media from chondrogenic and osteogenic cell pellets and undifferentiated cells was applied to endothelial tube formation assays using Matrigel™. Additionally, the cell secretome was analysed using LC-MS/MS mass spectrometry and screened for angiogenesis and neurogenesis-related factors using protein arrays. Endothelial tube-like formation was supported by conditioned media from undifferentiated eBMSCs. Conversely, chondrogenic and osteogenic conditioned media was antiangiogenic as shown by significantly decreased length of endothelial tube-like structures and degree of branching compared to controls. Undifferentiated cells produced higher levels of angiogenesis-related proteins compared to chondrogenic and osteogenic pellets. In summary, eBMSCs produce an array of angiogenesis-related proteins and support angiogenesis in vitro via a paracrine mechanism. However, when these cells are differentiated chondrogenically or osteogenically, they produce a soluble factor(s) that inhibits angiogenesis. With respect to osteochondral tissue engineering, this may be beneficial for avascular articular cartilage formation but unfavourable for bone formation where a vascularized tissue is desired.

Naturally occurring plant polyphenols as potential therapies for inherited neuromuscular diseases.

There are several lines of laboratory-based evidence emerging to suggest that purified polyphenol compounds such as resveratrol, found naturally in red grapes, epigallocatechin galate from green tea and curcumin from turmeric, might be useful for the treatment of various inherited neuromuscular diseases, including spinal muscular atrophy, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. Here, we critically examine the scientific evidence related to the known molecular effects that these polyphenols have on different models of inherited neuromuscular disease, with particular attention to problems with the validity of in vitro evidence. We also present proteomic evidence that polyphenols have in vitro effects on cells related to metal ion chelation in cell-culture media. Although their precise mechanisms of action remain somewhat elusive, polyphenols could be an attractive approach to therapy for inherited neuromuscular disease, especially since they may be safer to use on young children, compared with some of the other drug candidates.

Valproate reduces collagen and osteonectin in cultured bone cells.

Valproate is a histone deacetylase (HDAC) inhibitor that was introduced more than 40 years ago and is commonly used to treat epilepsy and mood disorders. Its long-term side effects can include bone loss, although the exact mechanism for this is currently unknown. In a previous study, we used iTRAQ labelling and mass spectrometry to profile the effect of valproate on skin fibroblast cells. We found, for the first time, that valproate reduced the amount of two key bone proteins; collagen I and osteonectin (SPARC, BM-40) while over 1000 other proteins remained unchanged (Fuller et al., 2010). We now show that valproate treatment also reduces the protein levels of collagen I and osteonectin in the hFOB1.19 osteoblast-like cell line. Pro-collagen I was reduced by 48% and osteonectin by 25% after 24h exposure to a clinically-relevant concentration of valproate. Collagen I is the main protein component of bone matrix and osteonectin has a major role in bone development and mineralisation, so reduced levels may contribute to bone loss following long-term in vivo exposure to valproate.

Muc5b is the major polymeric mucin in mucus from thoroughbred horses with and without airway mucus accumulation.

Mucus accumulation is a feature of inflammatory airway disease in the horse and has been associated with reduced performance in racehorses. In this study, we have analysed the two major airways gel-forming mucins Muc5b and Muc5ac in respect of their site of synthesis, their biochemical properties, and their amounts in mucus from healthy horses and from horses with signs of airway mucus accumulation. Polyclonal antisera directed against equine Muc5b and Muc5ac were raised and characterised. Immunohistochemical staining of normal equine trachea showed that Muc5ac and Muc5b are produced by cells in the submucosal glands, as well as surface epithelial goblet cells. Western blotting after agarose gel electrophoresis of airway mucus from healthy horses, and horses with mucus accumulation, was used to determine the amounts of these two mucins in tracheal wash samples. The results showed that in healthy horses Muc5b was the predominant mucin with small amounts of Muc5ac. The amounts of Muc5b and Muc5ac were both dramatically increased in samples collected from horses with high mucus scores as determined visually at the time of endoscopy and that this increase also correlated with increase number of bacteria present in the sample. The change in amount of Muc5b and Muc5ac indicates that Muc5b remains the most abundant mucin in mucus. In summary, we have developed mucin specific polyclonal antibodies, which have allowed us to show that there is a significant increase in Muc5b and Muc5ac in mucus accumulated in equine airways and these increases correlated with the numbers of bacteria.

Demonstration of dynorphin A 1-8 immunoreactive axons contacting spinal cord projection neurons in a rat model of peripheral inflammation and hyperalgesia.

Using a double-labeling technique, we evaluated the input of afferents immunoreactive for dynorphin peptide onto a population of lumbar spinal neurons contributing to the spinoparabrachial tract in rats with 1 inflamed hind paw. We found that the frequency and distribution with which dynorphin immunoreactive varicosities were in apposition to projection neurons varied according to neuron location. In particular, neurons in the superficial dorsal horn and neck of the dorsal horn receive a high degree of dynorphin input. We also determine that unilateral peripheral inflammation is associated with both an increase in the number of projection neurons receiving detectable DYN input and in the frequency of this input onto a given neuron, with the largest increase seen in the superficial dorsal horn. Since almost all superficial dorsal horn neurons contributing to the spinoparabrachial tract respond either exclusively or maximally to noxious stimulation, our data supports dynorphin's involvement in nociception.