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Background: Arthroscopic diagnosis and treatment of femoroacetabular pathology has experienced significant growth in the last 30 years; nevertheless, reduced utilization of orthopaedic procedures has been observed among the underrepresented population., Purpose/hypothesis: The purpose of this study was to examine racial differences in case incidence rates, outcomes, and complications in patients undergoing hip arthroscopy. It was hypothesized that racial and ethnic minority patients would undergo hip arthroscopy at a decreased rate compared with their White counterparts but that there would be no differences in clinical outcomes., Study Design: Cross-sectional study., Methods: The State Ambulatory Surgery and Services Database and the State Emergency Department Database of New York were queried for patients undergoing hip arthroscopy between 2011 and 2017. Patients were stratified into White and racial and ethnic minority races, and intergroup comparisons were performed for utilization over time, total charges billed per encounter, 90-day emergency department (ED) visits, and revision hip arthroscopy. Temporal trends in the utilization of hip arthroscopy were identified, and racial differences in secondary outcomes were analyzed with a semiparametric method known as targeted maximum likelihood estimation (TMLE) backed by a library of machine learning algorithms., Results: A total of 9745 patients underwent hip arthroscopy during the study period, with 1081 patients of minority race (11.1%). White patients underwent hip arthroscopy at 5.68 (95% CI, 4.98-6.48) times the incidence rate of racial and ethnic minority patients; these incidence rates grew annually at a ratio of 1.11 in White patients compared with 1.03 in racial and ethnic minority patients ( P < .001). Based on the TMLE, racial and ethnic minority patients were significantly more likely to incur higher costs ( P < .001) and visit the ED within 90 days ( P = .049) but had negligible differences in reoperation rates at a 2-year follow-up ( P = .53). Subgroup analysis identified that higher likelihood for 90-day ED admissions among racial and ethnic minority patients compared with White patients was associated with Medicare insurance ( P = .002), median income in the lowest quartile ( P = .012), and residence in low-income neighborhoods ( P = .006)., Conclusion: Irrespective of insurance status, racial and ethnic minority patients undergo hip arthroscopy at a lower incidence and incur higher costs per surgical encounter., Competing Interests: One or more of the authors has declared the following conflict of interest or source of funding: E.M.M. has received education payments from Exactech and hospitality payments from Stryker. M.D. has received hospitality payments from Stryker. M.H. has received education payments from Arthrex, Foundation Medical, Medwest Associates, and Smith+Nephew; honoraria from Encore Medical; hospitality payments from Orthalign and Medical Device Business Services; and consulting fees from Vericel. B.A.L. has received consulting fees from Arthrex and Smith+Nephew; nonconsulting fees from Arthrex, Smith+Nephew, and Linvatec; and royalties or license payments from Arthrex. A.J.K. has received nonconsulting fees from Arthrex; royalties or license payments from Arthrex; consulting fees from Arthrex, JRF Ortho, and Responsive Arthroscopy; a grant from DJO; and honoraria from JRF Ortho and MTF Biologics. K.R.O. has received education payments from Foundation Medical, Gemini Medical, Arthrex, Endo Pharmaceuticals, Pinnacle, Medwest Associates, and Smith+Nephew; nonconsulting fees from Smith+Nephew, Arthrex, and Medical Device Business Services; hospitality payments from Stryker, Arthrex, Wright Medical Technology, Medical Device Business Services, and Zimmer Biomet Holdings; consulting fees from Endo Pharmaceuticals and Smith+Nephew; and a grant from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© 2024 The Author(s).)

Purpose: To compare 3 separate blood flow restriction (BFR) systems in their capacity to reduce repetitions to failure, impact perceptual responses, and cause adverse events during a low-load free-flow exercise., Methods: The study included healthy subjects aged 18 years or older who presented to an ambulatory-care sports medicine clinic. On day 1, participants' demographic characteristics and anthropomorphic measurements were recorded. Each participant performed dumbbell biceps curl repetitions to failure using 20% of his or her 1-repetition maximum weight with each arm. Participants were exposed to 3 different tourniquet systems for familiarization. On day 2, each participant's arm was randomized to a cuff system, and the participant performed 2 sets of biceps curl repetitions to failure with the cuff inflated. Repetitions to failure, rating of perceived effort (RPE), rating of perceived discomfort, and pulse oxygenation levels were recorded after each set. On day 3, participants completed a survey of their perceived delayed-onset muscle soreness., Results: The final analysis was performed on 42 arms, with 14 limbs per system. The study population had a mean age of 28.7 ± 2.4 years and a mean body mass index of 24.9 ± 4.3. All 3 systems successfully reduced repetitions to failure compared with unrestricted low-load exercise from baseline to BFR set 1 and from baseline to BFR set 2. There were no significant between-group differences among BFR systems regarding the number of repetitions to failure performed at baseline versus BFR set 1 or BFR set 2. The Delfi Personalized Tourniquet System (PTS) cohort had the greatest reductions in repetitions to failure from BFR set 1 to BFR set 2 ( P  = .002) and reported the highest RPE after set 2 ( P  = .025)., Conclusions: The Delfi PTS, SmartCuffs Pro, and BStrong BFR systems were each safe and were able to significantly reduce repetitions to failure compared with a low-load free-flow condition when used in a BFR exercise protocol. The Delfi PTS system may produce a higher RPE with prolonged use in comparison to the other systems., Level of Evidence: Level II, prospective cohort study., (© 2023 The Authors.)

Introduction: Diabetes mellitus (DM) impairs fracture healing and is associated with susceptibility to infection, which further inhibits fracture healing. While intermittent parathyroid hormone (1-34) (iPTH) effectively improves fracture healing, it is unknown whether infection-associated impaired fracture healing can be rescued with PTH (teriparatide)., Methods: A chronic diet-induced type 2 diabetic mouse model was used to yield mice with decreased glucose tolerance and increased blood glucose levels compared to lean-fed controls. Methicillin-resistant Staphylococcus aureus (MRSA) was inoculated in a surgical tibia fracture model to simulate infected fracture, after which mice were treated with a combination of antibiotics and adjunctive teriparatide treatment. Fracture healing was assessed by Radiographic Union Scale in Tibial Fractures (RUST), micro-computed tomography (μCT), biomechanical testing, and histology., Results: RUST score was significantly poorer in diabetic mice compared to their lean nondiabetic counterparts. There were concomitant reductions in micro-computed tomography (μCT) parameters of callus architecture including bone volume/total volume, trabecular thickness, and total mineral density in type 2 diabetes mellitus (T2DM) mice. Biomechanicaltesting of fractured femora demonstrated diminished torsional rigidity, stiffness, and toughness to max torque. Adjuvant teriparatide treatment with systemic antibiotic therapy improved numerous parameters of bone microarchitecture bone volume, increased connectivity density, and increased trabecular number in both the lean and T2DM group. Despite the observation that poor fracture healing in T2DM mice was further impaired by MRSA infection, adjuvant iPTH treatment significantly improved fracture healing compared to antibiotic treatment alone in infected T2DM fractures., Discussion: Our results suggest that teriparatide may constitute a viable adjuvant therapeutic agent to improve bony union and bone microarchitecture to prevent the development of septic nonunion under diabetic conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kwon, Cahill, Yu, Alder, Dussik, Jeong, Back and Lee.)

Despite the development of various therapeutic options, surgical management of irreparable rotator cuff tears (IRCTs) remains controversial. Recently, implantation of a biodegradable subacromial balloon spacer (InSpace, Stryker Corporation; Kalamazoo, MI) has gained considerable interest for the treatment of certain IRCTs. The reported outcome of balloon implantation has not been consistent, likely due to differing indications and technical approaches. The purpose of this article is to present a reproducible arthroscopic technique for implantation of a subacromial balloon and to review the literature published to date, regarding the efficacy and outcomes of this procedure., (© 2023 The Authors.)

Background Osteolytic neoplasms to periacetabular bone frequently cause pain and fractures. Immediate recovery is integral to lifesaving ambulatory oncologic care and maintaining quality of life. Yet, open acetabular reconstructive surgeries are associated with numerous complications that delay cancer treatments. Purpose To determine the effectiveness for short- and long-term pain and ambulatory function following percutaneous ablation, osteoplasty, reinforcement, and internal fixation (AORIF) for periacetabular osteolytic neoplasm. Materials and Methods This retrospective observational study evaluated clinical data from 50 patients (mean age, 65 years ± 14 [SD]; 25 men, 25 women) with osteolytic periacetabular metastases or myeloma. The primary outcome of combined pain and ambulatory function index score (range, 1 [bedbound] through 10 [normal ambulation]) was assessed before and after AORIF at 2 weeks and then every 3 months up to 40 months (overall median follow-up, 11 months [IQR, 4-14 months]). Secondary outcomes included Eastern Cooperative Oncology Group (ECOG) score, infection, transfusion, 30-day readmission, mortality, and conversion hip arthroplasty. Serial radiographs and CT images were obtained to assess the hip joint integrity. The paired t test or Wilcoxon signed-rank test and Kaplan-Meier analysis were used to analyze data. Results Mean combined pain and ambulatory function index scores improved from 4.5 ± 2.4 to 7.8 ± 2.1 ( P < .001) and median ECOG scores from 3 (IQR, 2-4) to 1 (IQR, 1-2) ( P < .001) at the first 2 weeks after AORIF. Of 22 nonambulatory patients, 19 became ambulatory on their first post-AORIF visit. Pain and functional improvement were retained beyond 1 year, up to 40 months after AORIF in surviving patients. No hardware failures, surgical site infections, readmissions, or delays in care were identified following AORIF. Of 12 patients with protrusio acetabuli, one patient required a conversion hemiarthroplasty at 24 months. Conclusion The ablation, osteoplasty, reinforcement, and internal fixation, or AORIF, technique was effective for short- and long-term improvement of pain and ambulatory function in patients with periacetabular osteolytic neoplasm. © RSNA, 2023.

To date, there has been a paucity of research evaluating the demographics, characteristics, and surgical training of orthopaedic residency program directors (PDs)., Purpose: To determine the objective characteristics of orthopaedic residency PDs by analyzing their demographic characteristics, academic backgrounds, institutional histories, research productivity, and professional leadership affiliations., Methods: Data for each PD were collected by searching publicly available curriculum vitae , LinkedIn, Healthgrades, Doximity, and/or institutional biographies and consolidated into a database. Research productivities were collected by searching PubMed and Scopus., Results: Of the 210 PDs, 188 (89.5%) were male and 22 (10.5%) were female. One hundred seventy-four (82.9%) were non-Hispanic White, 14 (6.7%) Asian American and Pacific Islander, 12 (5.7%) Black or African American, 4 (1.9%) Hispanic or Latino, and 6 (2.9%) other/unknown. Twenty-four (11.4%) PDs had a military affiliation. Moreover, the most common subspecialties among orthopaedic PDs were orthopaedic traumatology (19.5%, n = 41), sports medicine (15.7%, n = 33), and hand surgery (11.9%, n = 25). The mean Scopus h -index, total number of publications at the time of data collection (June 2022), and total number of citations for all orthopaedic residency PDs were 10.5 ± 9.5, 33.9 ± 51.0, and 801.9 ± 1,536.4, respectively. Among all PDs, the mean tenure in the position was 8.9 ± 6.2 years to date, and the mean time from completion of residency to appointment as PD was 10.0 ± 6.2 years., Conclusions: Among orthopaedic surgery residency PDs, there is sparse female and minority representation. Overarchingly, orthopaedic PDs are White men in their early 50s. Moreover, 59.1% of PDs were appointed at an institution where they completed medical school, residency, or fellowship. orthopaedic traumatology (19.5%), sports medicine (15.7%), and hand surgery (11.9%) were the subspecialties most represented in current orthopaedic surgery PDs., Clinical Relevance: This study outlines important demographic characteristics among orthopaedic surgery residency PDs., Level of Evidence: III., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Intracellular infiltration of bacteria into host cells complicates medical and surgical treatment of bacterial joint infections. Unlike soft tissue infections, septic arthritis and infection-associated inflammation destroy cartilage that does not regenerate once damaged. Herein, we show that glycolytic pathways are shared by methicillin-resistant Staphylococcus aureus (MRSA) proliferation and host inflammatory machinery in septic arthritis. MRSA readily penetrates host cells and induces proinflammatory cascades that persist after conventional antibiotic treatment. The glycolysis-targeting drug dimethyl fumarate (DMF) showed both bacteriostatic and anti-inflammatory effects by hindering the proliferation of intracellular MRSA and dampening excessive intraarticular inflammation. Combinatorial treatment with DMF and vancomycin further reduced the proliferation and re-emergence of intracellular MRSA. Combinatorial adjuvant administration of DMF with antibiotics alleviated clinical symptoms of septic arthritis by suppressing bacterial burden and curbing inflammation to protect cartilage and bone. Our results provide mechanistic insight into the regulation of glycolysis in the context of infection and host inflammation toward development of a novel therapeutic paradigm to ameliorate joint bioburden and destruction in septic arthritis., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Fracture healing is impaired in the setting of infection, which begets protracted inflammation. The most problematic causative agent of musculoskeletal infection is methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that modulation of excessive inflammation combined with cell-penetrating antibiotic treatments facilitates fracture healing in a murine MRSA-infected femoral fracture model. Sterile and MRSA-contaminated open transverse femoral osteotomies were induced in 10-week-old male C57BL/6 mice and fixed via intramedullary nailing. In the initial therapeutic cohort, empty, vancomycin (V), rifampin (R), vancomycin-rifampin (VR), or vancomycin-rifampin-trametinib (VRT) hydrogels were applied to the fracture site intraoperatively. Rifampin was included because of its ability to penetrate eukaryotic cells to target intracellular bacteria. Unbiased screening demonstrated ERK activation was upregulated in the setting of MRSA infection. As such, the FDA-approved mitogen-activated protein kinase kinase (MEK)1-pERK1/2 inhibitor trametinib was evaluated as an adjunctive therapeutic agent to selectively mitigate excessive inflammation after infected fracture. Two additional cohorts were created mimicking immediate and delayed postoperative antibiotic administration. Systemic vancomycin or VR was administered for 2 weeks, followed by 2 weeks of VRT hydrogel or oral trametinib therapy. Hematologic, histological, and cytokine analyses were performed using serum and tissue isolates obtained at distinct postoperative intervals. Radiography and micro-computed tomography (μCT) were employed to assess fracture healing. Pro-inflammatory cytokine levels remained elevated in MRSA-infected mice with antibiotic treatment alone, but increasingly normalized with trametinib therapy. Impaired callus formation and malunion were consistently observed in the MRSA-infected groups and was partially salvaged with systemic antibiotic treatment alone. Mice that received VR alongside adjuvant MEK1-pERK1/2 inhibition displayed the greatest restoration of bone and osseous union. A combinatorial approach involving adjuvant cell-penetrating antibiotic treatments alongside mitigation of excessive inflammation enhanced healing of infected fractures. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation, thereby predisposing patients to pathological fracture and cancer growth. Alteration of osteoblast function induces skeletal diseases due to the disruption of bone homeostasis. We observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer metastases. We confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer interface. The process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within bone. Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment., (© 2021. The Author(s).)

Bacterial infections involving joints and vital organs represent a challenging clinical problem because of the two concurrent therapeutic goals of bacterial eradication and tissue preservation. In the case of septic arthritis, permanent destruction of articular cartilage by intense host inflammation is commonly seen even after successful treatment of bacterial infection. Here, we provide scientific evidence of a novel treatment modality that can protect articular cartilage and enhanced eradication of causative bacteria in septic arthritis. Locally delivered cell-penetrating antibiotics such as rifampicin effectively eradicate intracellular reservoirs of methicillin-resistant Staphylococcus aureus within joint cells. Furthermore, mitigation of intra-articular inflammation by targeting the NLRP3 (nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3) inflammasome protects articular cartilage from damage in a murine model of knee septic arthritis. Together, concurrent mitigation of intra-articular inflammation and local adjuvant targeting of intracellular bacteria represents a promising new therapeutic strategy for septic arthritis., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Introduction: Postoperative delirium is common for patients with hip fracture. Predictors of postoperative delirium and its association with preexisting dementia and adverse postoperative outcomes in a geriatric hip fracture population were assessed., Methods: Patients with hip fracture aged 60 years and older were identified in the 2016 and 2017 National Surgical Quality Improvement Program Procedure Targeted Databases. Independent risk factors of postoperative delirium were identified. Associations with mortality, readmission, and revision surgery were evaluated using moderation and mediation analysis., Results: Of 18,754 patients with hip fracture, 30.2% had preoperative dementia, 18.8% had postoperative delirium, and 8.3% had both preoperative dementia and postoperative delirium. Independent predictors of postoperative delirium were as follows: older age, male sex, higher American Society of Anesthesiologists score, dependent functional status, nongeneral anesthesia, preoperative diabetes, bleeding disorder, and preoperative dementia. Preoperative dementia and postoperative delirium each had an independent correlation with 30-day mortality (odds ratios = 2.06 and 1.92, respectively, with P < 0.001 for both). However, when both were present, those with preoperative dementia and postoperative delirium had an even higher odds of mortality based on moderation analysis (odds ratio = 2.25, P < 0.001). Readmissions and reoperations were significantly correlated with postoperative delirium, but not with preoperative dementia. The combination of preoperative dementia and postoperative delirium, however, did have compounding effects. Furthermore, a significant proportion of the total effect of preoperative dementia on mortality and readmission was accounted for by the development of postoperative delirium based on mediation analysis (medeff: 7%, P < 0.001 and medeff: 35%, P < 0.001)., Discussion: Postoperative delirium is a potentially preventable postoperative adverse outcome that was seen in 18.8% of 18,754 patients with hip fracture. Those with preoperative dementia seem to be a particularly at-risk subpopulation. Quality improvement initiatives to minimize postoperative delirium in this hip fracture population should be considered and optimized., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (μCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. μCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR)., (© 2020 American Society for Bone and Mineral Research (ASBMR).)

Naringin is a naturally occurring flavonoid found in plants of the Citrus genus that has historically been used in traditional Chinese medical regimens for the treatment of osteoporosis. Naringin modulates signaling through numerous molecular pathways critical to musculoskeletal development, cellular differentiation, and inflammation. Administration of naringin increases in vitro expression of bone morphogenetic proteins (BMPs) and activation of the Wnt/β-catenin and extracellular signal-related kinase (Erk) pathways, thereby promoting osteoblastic proliferation and differentiation from stem cell precursors for bone formation. Naringin also inhibits osteoclastogenesis by both modifying RANK/RANKL interactions and inducing apoptosis in osteoclasts in vitro . In addition, naringin acts on the estrogen receptor in bone to mimic the native bone-preserving effects of estrogen, with few systemic side effects on other estrogen-sensitive tissues. The efficacy of naringin therapy in reducing the osteolysis characteristic of common musculoskeletal pathologies such as osteoporosis, degenerative joint disease, and osteomyelitis, as well as inflammatory conditions affecting bone such as diabetes mellitus, has been extensively demonstrated in vitro and in animal models. Naringin thus represents a naturally abundant, cost-efficient agent whose potential for use in novel musculoskeletal biotherapies warrants re-visiting and further exploration through human studies. Here, we review the cellular mechanisms of action that have been elucidated regarding the action of naringin on bone resident cells and the bone microenvironment, in vivo evidence of naringin's osteostimulative and chondroprotective properties in the setting of osteolytic bone disease, and current limitations in the development of naringin-containing translational therapies for common musculoskeletal conditions., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background: Postoperative stroke is a rare but potentially devastating complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of the current study was to determine the incidence, independent risk factors, and timing of stroke following THA and TKA utilizing the National Surgical Quality Improvement (NSQIP) database., Methods: Patients who underwent elective primary THA and TKA were identified in the 2005-2016 NSQIP database. Thirty-day postoperative strokes were identified, timing was characterized, and an incidence curve was created. Multivariate analyses determined the independent predictors of these strokes., Results: Of 333,117 patients identified, 286 (0.09%) experienced a stroke. Given that THA vs TKA was not a univariate predictor of stroke, the two procedures were considered together. The majority (65%) of strokes occurred before discharge. Of the strokes observed, 25% occurred by postoperative day one, 50% by postoperative day two, and 75% by postoperative day nine. Independent risk factors for postoperative stroke were: age (60-69 years old odds ratio [OR] = 4.2; 70-79 years old OR = 8.1; ≤80 years old OR = 16.1), higher American Society of Anesthesiologists (ASA) score (ASA≥3 OR = 1.7), and smoking [OR = 1.6)., Conclusion: The incidence of stroke after THA/TKA was low at 0.09%, with the majority occurring prior to discharge and half occurring by postoperative day two. Patients who were older, sicker, or who were smokers were at greater risk of postoperative stroke. These findings can be used to council patients and to optimize patient care., Level of Evidence: Level III, Retrospective comparative study., Competing Interests: Competing interests include personal fees from TIDI Products and North American Spine Society Fellow of the American College of Surgeons. These interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Type 2 diabetes mellitus (T2DM) is a multisystemic disease that afflicts more than 415 million people globally-the incidence and prevalence of T2DM continues to rise. It is well-known that T2DM has detrimental effects on bone quality that increase skeletal fragility, which predisposes subjects to an increased risk of fracture and fracture healing that results in non- or malunion. Diabetics have been found to have perturbations in metabolism, hormone production, and calcium homeostasis-particularly PTH expression-that contribute to the increased risk of fracture and decreased fracture healing. Given the perturbations in PTH expression and the establishment of hPTH (1-34) for use in age-related osteoporosis, it was determined logical to attempt to ameliorate the bone phenotype found in T2DM using hPTH (1-34). Therefore, the present study had two aims: (i) to establish a suitable murine model of the skeletal fragility present in T2DM because no current consensus model exists; and (ii) to determine the effects of hPTH (1-34) on bone fractures in T2DM. The results of the present study suggest that the polygenic mouse of T2DM, TALLYHO/JngJ, most accurately recapitulates the diabetic osteoporotic phenotype seen in humans and that the intermittent systemic administration of hPTH (1-34) increases fracture healing in T2DM murine models by increasing the proliferation of mesenchymal stem cells. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.)

Endothelin-1 (ET-1) is a peptide hormone that functions as a vasoconstrictor in the vasculature, whereas in the collecting duct of the kidney it exerts blood pressure-lowering effects via natriuretic actions. Aberrant ET-1 signaling is associated with several pathological states including hypertension and chronic kidney disease. ET-1 expression is regulated largely through transcriptional control of the gene that encodes ET-1, EDN1 . Here we report a long, non-coding RNA (lncRNA) that appears to be antisense to the EDN1 gene, called EDN1-AS . Because EDN1-AS represents a potential novel mechanism to regulate ET-1 expression, we examined the regulation of EDN1-AS expression and action. A putative glucocorticoid receptor response (GR) element upstream of the predicted EDN1-AS transcription start site was identified using the ENCODE database and the UCSC genome browser. Two homozygous deletion clones of the element were generated using CRISPR/Cas9. This deletion resulted in a significant increase in the expression of EDN1-AS , which was associated with increased secretion of ET-1 peptide from HK-2 cells (two-fold increase in KO cells vs. CNTL, n = 7, P < 0.05). Phenotypic characterization of these CRISPR clones revealed a difference in cell growth rates. Using a standard growth assay, we determined that the KO1 clone exhibited a three-fold increase in growth over 8 days compared to control cells ( n = 4, P < 0.01) and the KO2 clone exhibited a two-fold increase ( n = 4, P < 0.01). These results support a role for EDN1-AS as a novel regulatory mechanism of ET-1 expression and cellular proliferation., (Copyright © 2020 Douma, Solocinski, Masten, Barral, Barilovits, Jeffers, Alder, Patel, Wingo, Brown, Cain and Gumz.)

There are many treatment modalities for benign cystic lesions of bone, but all methods, except for total resection, are plagued with varying rates of recurrence 1 . Thorough curettage with the use of a high-speed burr, however, has demonstrated a low recurrence rate of 12% and has been suggested to be the best method for the treatment of benign cystic lesions. Approximately 90% of aneurysmal bone cysts can be controlled adequately with this treatment alone 2 ., Description: Treatment of benign cystic lesions of bone with the use of excisional curettage requires careful preoperative planning and patient positioning before the initial incision is made. The initial incision must be carefully planned to expose the entire lesion without violating multiple compartments unnecessarily. A sizeable cortical window must then be made using a high-speed burr followed by evacuation of all cystic contents via curettage. The cavity is copiously irrigated before an adjuvant is used, and the lesion is stabilized, if necessary, before closing., Alternatives: There are many types of alternatives to curettage, such as wide resection, radiation, and embolization of feeding vessels., Rationale: In orthopaedics, as in all medical specialties, many interventions and techniques have been rendered obsolete and, ultimately, replaced by newer, safer, and more efficient ones. The appeal of curettage has remained because of its procedural simplicity and adaptability in the management of a plethora of diseases such as benign cystic lesions of bone. Additionally, curettage, unlike wide resection, radiation, and embolization of feeding vessels, is minimally invasive and often definitive in nature when used as a treatment modality 2 . Lastly, curettage grants the performing surgeon the ability to maintain a contained cavity that can be treated with a variety of adjuvant therapies 3-17 . These reasons listed above make curettage a viable option for the surgical treatment of benign cystic lesions such as giant cell tumors of bone, aneurysmal bone cysts, unicameral bone cysts, chondromyxoid fibromas, and symptomatic nonossifying fibromas., (Copyright © 2019 by The Journal of Bone and Joint Surgery, Incorporated.)