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At the present time there are no consistently satisfactory treatment options for some challenging bone loss scenarios. We have previously reported on the properties of a novel 3D-printed hydroxyapatite-composite material in a pilot study, which demonstrated osteoconductive properties but was not tested in a rigorous, clinically relevant model. We therefore utilized a rat critical-sized femoral defect model with a scaffold designed to match the dimensions of the bone defect. The scaffolds were implanted in the bone defect after being loaded with cultured rat bone marrow cells (rBMC) transduced with a lentiviral vector carrying the cDNA for BMP-2. This experimental group was compared against 3 negative and positive control groups. The experimental group and positive control group loaded with rhBMP-2 demonstrated statistically equivalent radiographic and histologic healing of the defect site (p > 0.9), and significantly superior to all three negative control groups (p < 0.01). However, the healed defects remained biomechanically inferior to the unoperated, contralateral femurs (p < 0.01). When combined with osteoinductive signals, the scaffolds facilitate new bone formation in the defect. However, the scaffold alone was not sufficient to promote adequate healing, suggesting that it is not substantially osteoinductive as currently structured. The combination of gene therapy with 3D-printed scaffolds is quite promising, but additional work is required to optimize scaffold geometry, cell dosage and delivery.

Background The purpose of this study is to assess the epidemiology, population-specific treatment trends, and complications of distal radius fractures in the United States. Methods The PearlDiver database (Humana [2007–2014], Medicare [2005–2014]) was used to access US inpatient and outpatient data for all patients who had undergone operative and nonoperative treatment for a distal radius fracture in the United States. Epidemiologic analysis was performed followed by age-based stratification, to assess prevalence, treatment trends, and rates of complications. Results A total of 1,124,060 distal radius treatment claims were captured. The incidence of distal radius fractures follows a bimodal distribution with distinct peaks in the pediatric and elderly population. Fractures in the pediatric population occurred predominately in males, whereas fractures in the elderly population occurred more frequently in females. The most commonly used modality of treatment was nonoperative; however, the use of internal fixation increased significantly during the study period, from 8.75 to 20.02%, with a corresponding decrease in percutaneous fixation. The overall complication rate was 8.3%, with mechanical symptoms most frequently reported. Conclusions The last decade has seen a significant increase in the use of internal fixation as treatment modality for distal radius fractures. The impetus for this change is likely multifactorial and partly related to recent innovations including volar locking plates and an increasingly active elderly population. The implicated financial cost must be weighed against the productivity cost of maintaining independent living to determine the true burden to the healthcare system.

Introduction The mainstay of trigger finger treatment is a corticosteroid injection of the affected digits and is associated with a very high success rate. However, some patients do not respond to nonsurgical management and undergo subsequent surgical release. The purpose of this study is to investigate the comorbidities that predispose patients to progressing from injection to surgical release. Methods Patient data were obtained from a national insurance database. All patients aged 20 years or older who underwent trigger digit injection were included. Any injection that did not specify the digit was excluded. Subsequent procedures, including repeat injection and surgical release, were identified using relevant Current Procedural Terminology codes. A multivariate model was constructed to evaluate potential risk factors for requiring release after prior injection of the same digit. Stepwise backward selection was used to retain significant variables. Results A total of 42,537 trigger digits were identified in 31,830 patients, most of whom were female. The right hand was affected more commonly than the left. The middle and ring fingers were the most commonly affected digits. Over 80% of all trigger digits underwent only a single injection, and approximately 90% of injected digits did not require subsequent release. In the multivariate model, factors associated with higher risk of release were male sex, involvement of additional digits, multiple injections of the same digit, chronic pulmonary disease, HIV/AIDS, obesity, alcohol abuse, and depression. The model also found small fingers to be less likely to progress to release. Discussion Patients with the risk factors identified in this study are more likely to progress to surgical release after trigger finger injection. Although prospective studies are required, the information may be beneficial in counseling patients and their treatment options.

Venous thromboembolic disease (VTE) is an infrequent but serious complication after total joint arthroplasty. The selection of an appropriate prophylaxis regimen is a balance between efficacy and safety. Risk stratification is the key to the selection of an appropriate prophylaxis regimen, but there is no ideal risk stratification protocol available today.

Background Total ankle arthroplasty is an increasingly effective option for the treatment of end-stage arthritis. One recent innovation utilizes a transfibular, lateral approach. Like any new system, there is likely a learning curve associated with its use. We analyzed a series of patients who received a total ankle arthroplasty via a transfibular approach to state if it is possible to identify and to evaluate effects of a learning curve in the use of this novel total ankle replacement system. Methods 76 consecutive patients meeting inclusion and exclusion criteria were retrospectively analyzed. All patients had a minimum of 24 months of follow-up. Intraoperative parameters, preoperative and postoperative subjective outcome scores, radiographic parameters, and complications were recorded and evaluated. Results There were significant learning curve effects on various surgical and postoperative parameters. Surgical time decreased with the curve stabilizing after the 16th patient. With regard to patient outcomes, a learning curve was identified for the VAS, AOFAS, and SF-12 MCS scores. The number of patients required to stabilize these curves were 21, 13, and 16, respectively. Alignment as measured by alpha and gamma angles also improved with experience, with the curves stabilizing at 18 and 15 patients, respectively. There was a larger number cases required for complication rates, with the curve stabilizing after the 39th patient. No significant learning curve was found for ankle ROM, SF-12 PCS, beta angle, tibio-talar ratio (TTR), or tibio-talar surface angle (TTS). Conclusions This study demonstrates a significant learning curve with respect to operative time, patient outcomes, and radiographic parameters. Extrapolating this information, we urge surgeons to adequately familiarize themselves with any new implant through a training program in a high-volume center. Level of evidence IV, case series.

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs)., National Institutes of Health (U.S.) (Grant R01 RHL115145A)

Introduction The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions. Aim The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging. Methods We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions. Main Outcome Measures Data reported in the literature were analyzed, reviewed, and discussed. Results DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7β DHEA, and 7α and 7β epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women. Conclusion DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be associated with a host of pathologies; however, the clinical efficacy of DHEA supplementation in ameliorating patho-physiological symptoms remains to be evaluated.

This study examined the reliability and validity of the 3-item Generic Brief Acculturation Scale (GBAS). The GBAS was administered as a part of a larger Navy Health Behavior Survey of male enlisted personnel deployed on aircraft carriers. Analyses are reported here for the subsample for whom English was a second language (n = 529, 15% of original sample). Generic Brief Acculturation Scale reliability was assessed with internal consistency. Validity was assessed using t test and correlation. Results supported reliability and validity: Cronbach alpha was .81, mean GBAS scores for US-born participants were significantly higher than that for foreign born (P < .05), and GBAS scores were positively correlated with generation (r = 0.34). Additional research with civilian populations is needed, but these findings suggest that the GBAS could be useful either as a quick screen in clinical practice to determine when a translator may be needed or to guide decision making regarding health promotion programming.