Efficacy of post-operative X-rays after operatively treated ankle fractures: What is their role?

OBJECTIVE: The utility of routine post-operative imaging in clinically asymptomatic patients is unclear. We sought to determine how frequently X-rays following operatively treated ankle fractures result in a change in management. DESIGN: Retrospective cohort study conducted with hospital electronic health record SETTING: Single level 1 trauma center in major urban city. PATIENTS/PARTICIPANTS: 193 patients with operatively treated ankle fractures at our institution between January 2020 and December 2021. MAIN OUTCOME MEASURES: Patient radiographs were categorized as surveillance X-rays and clinically indicated X-rays. Changes in management were defined as alteration in follow-up, deviation from standard post-operative protocols, or revision surgery. A logistic regression was performed looking at factors predicting whether an X-ray changes management. A cost analysis was also performed looking at the financial implications of asymptomatic surveillance of ankle fractures. RESULTS: 438 post-operative X-rays were found and included in analysis. Of these, 391 were considered surveillance X-rays and 47 clinically indicated. 23 X-rays were determined to have resulted in changes in management (18 clinically indicated, 5 taken in asymptomatic patients). The number of management changing X-rays was significantly higher in the clinically indicated group (p < 0.0001). The only factor associated with whether an X-ray changed management was whether the patient was symptomatic at the visit (p < 0.0001). Asymptomatic surveillance X-rays cost our institution 21,825.62 USD per year. CONCLUSIONS: Radiographs in clinically asymptomatic patients with operatively managed ankle fractures have a low likelihood of changing management. Such imaging represents costs to the healthcare system, increased time for patients during clinic visits, and radiation exposure. The use of screening radiographic studies remains commonplace because the risk of delayed diagnosis is great, and the goal of any surgeon should be the swift identification of complications in order to minimize patient morbidity. Future surveillance protocols should consider the findings of this and other studies on the use of screening radiographs and strike a careful balance between minimizing unnecessary imaging, maximizing early complication detection, and ensuring a personalized approach towards patient-level factors to optimize care and efficiency for both patient and health system. LEVEL OF EVIDENCE: Level III.

Forgetting the Frail: National Trends in Vitamin D Prescription After Fragility Fracture-A Large Insurance Claims Database Study.

INTRODUCTION: Vitamin D plays a critical role in bone health, affecting bone mineral density and fracture healing. Insufficient serum vitamin D levels are associated with increased fracture rates. Despite guidelines advocating vitamin D supplementation, little is known about the prescription rates after fragility fractures. This study aims to characterize vitamin D prescription rates after three common fragility fractures in patients older than 50 years and explore potential factors influencing prescription rates. METHODS: The study used the PearlDiver Database, identifying patients older than 50 years with hip fractures, spinal compression fractures, or distal radius fractures between 2010 and 2020. Patient demographics, comorbidities, and vitamin D prescription rates were analyzed. Statistical methods included chi-square analysis and univariate and multivariable analyses. RESULTS: A total of 3,214,294 patients with fragility fractures were included. Vitamin D prescriptions increased from 2.50% to nearly 6% for all fracture types from 2010 to 2020. Regional variations existed, with the Midwest having the highest prescription rate (4.25%) and the West the lowest (3.31%). Patients with comorbidities such as diabetes, tobacco use, obesity, female sex, age older than 60 years, and osteoporosis were more likely to receive vitamin D prescriptions. DISCUSSION: Despite a notable increase in vitamin D prescriptions after fragility fractures, the absolute rates remain low. Patient comorbidities influenced prescription rates, perhaps indicating growing awareness of the link between vitamin D deficiency and these conditions. However, individuals older than 60 years, a high-risk group, were markedly less likely to receive prescriptions, possibly because of practice variations and concerns about polypharmacy. Educational initiatives and revised guidelines may have improved vitamin D prescription rates after fragility fractures. However, there is a need to raise awareness about the importance of vitamin D for bone health, particularly in older adults, and additional study variations in prescription practices. These findings emphasize the importance of enhancing post-fracture care to reduce morbidity and mortality associated with fragility fractures. LEVEL OF EVIDENCE: III.

Depression, anxiety, and post-traumatic stress disorder following upper versus lower extremity fractures.

INTRODUCTION: Orthopaedic trauma has been linked to major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Post-injury rates of psychiatric diagnoses and their relationship to various injury characteristics are not well characterized. We aimed to determine the association between orthopaedic trauma and MDD, GAD, and PTSD diagnoses at 5-year follow-up. METHODS: A national insurance claims database was used to create upper extremity fracture (UEF) and lower extremity fracture (LEF) cohorts, with further stratification by isolated versus multiple fractures. Patient undergoing elective upper or lower extremity orthopaedic procedures served as controls. Rates of post-injury psychiatric diagnoses were calculated. Univariate logistic regression was conducted after matching in a 1:1 ratio based on relevant comorbidities such as psychiatric history. All significant variables were included in multivariate analysis. RESULTS: A total of 308,578 UEF patients and 360,510 LEF patients were identified. Within the UEF cohort, the diagnosis rates following either isolated or multiple fractures were identified: MDD (25% to 30%), GAD (10% to 11%), and PTSD (4%). LEF cohort rates were as follows: MDD (30% to 38%), GAD (11% to 14%), and PTSD (4% to 7%). Compared to non-injured controls, both the UEF and LEF cohorts were associated with higher rates of all psychiatric diagnoses. In comparing UEF and LEF cohorts, isolated UEF was associated with MDD, GAD, and PTSD; however, multiple UEF was associated with MDD and GAD, whereas multiple LEF was associated with PTSD. CONCLUSION: Psychiatric pathology is prevalent following orthopaedic trauma. Even after controlling for psychiatric history, orthopaedic trauma is independently associated with post-injury psychiatric diagnoses and may be more predictive of PTSD and GAD than of MDD. Upper extremity fractures may portend higher psychiatric risk. With negative stigma surrounding mental health and the early role of orthopaedic surgeons in providing care, it is imperative to normalize psychiatric care with patients and discuss warning symptoms that may indicate the onset of psychiatric disorders. LEVEL OF EVIDENCE: Prognostic, Level III.

ChatGPT's Ability to Assist with Clinical Documentation: A Randomized Controlled Trial.

INTRODUCTION: Clinical documentation is a critical aspect of health care that enables healthcare providers to communicate effectively with each other and maintain accurate patient care records. Artificial intelligence tools, such as chatbots and virtual assistants, have the potential to assist healthcare providers in clinical documentation. ChatGPT is an artificial intelligence conversational model that generates human-like responses to text-based prompts. In this study, we sought to investigate ChatGPT's ability to assist with writing a history of present illness based on standardized patient histories. METHODS: A blinded, randomized controlled study was conducted to compare the use of typing, dictation, and ChatGPT as tools to document history of present illness (HPI) of standardized patient histories. Eleven study participants, consisting of medical students, orthopaedic surgery residents, and attending surgeons, completed three HPIs using a different documentation technique for each one. Participants were randomized into cohorts based on the type of documentation technique. Participants were asked to interview standardized patients and document the patient's history of present illness using their assigned method. RESULTS: ChatGPT was found to be intermediate for speed; dictation was fastest, but produced markedly longer and higher quality patient histories based on Physician Documentation Quality Instrument score compared with dictation and typing. However, ChatGPT included erroneous information in 36% of the documents. Poor agreement existed on the quality of patient histories between reviewers. DISCUSSION: Our study suggests that ChatGPT has the potential to improve clinical documentation by producing more comprehensive and organized HPIs. ChatGPT can generate longer and more detailed documentation compared with typing or dictation documentation methods. However, additional studies are needed to investigate and address concerns regarding privacy, bias, and accuracy of information.

Are Social Deprivation and Low Traditional Health Literacy Associated With Higher PROMIS CAT Completion in Orthopaedic Surgery?

BACKGROUND: The Patient-Reported Outcomes Measurement Information System® (PROMIS®) may be used to assess an individual patient's perspective of their physical, mental, and social health through either standard or computer adaptive testing (CAT) patient questionnaires. These questionnaires are used across disciplines; however, they have seen considerable application in orthopaedic surgery. Patient characteristics associated with PROMIS CAT completion have not been examined within the context of social determinants of health, such as social deprivation or health literacy, nor has patient understanding of the content of PROMIS CAT been assessed. QUESTIONS/PURPOSES: (1) What patient demographics, including social deprivation, are associated with completion of PROMIS CAT questionnaires? (2) Is health literacy level associated with completion of PROMIS CAT questionnaires? (3) Do patients with lower health literacy have a higher odds of completing PROMIS CAT without fully understanding the content? METHODS: Between June 2022 and August 2022, a cross-sectional study was performed via a paper survey administered to patients at a single, urban, quaternary academic medical center in orthopaedic subspecialty clinics of foot and ankle, trauma, and hand/upper extremity surgeons. We considered all English-speaking patients aged 18 or older, including those with limited reading and/or writing abilities, as eligible provided they received an iPad in clinic to complete the PROMIS CAT questionnaire as part of their routine standard clinical care or they completed the questionnaire via a patient portal before the visit. In all, 946 patients were considered eligible during the study period and a convenience sample of 36% (339 of 946) of patients was approached for inclusion due to clinic time constraints. Fifteen percent (52 of 339) declined to participate, leaving 85% (287 of 339) of patients for analysis here. Median (range) age of study participants was 49 years (35 to 64). Fifty-eight percent (167 of 287) of study participants self-identified as non-Hispanic Black or African American and 26% (75 of 287) as non-Hispanic White. Even proportions were observed across education levels (high school graduate or less, 29% [82 of 287]; some college, 25% [73 of 287]; college graduate, 25% [71 of 287]; advanced degree, 20% [58 of 287]). Eighteen percent (52 of 287) of patients reported an annual income bracket of USD 0 to 13,000, and 17% (48 of 287) reported more than USD 120,000. Forty-six percent (132 of 287) of patients worked full-time, 21% (59 of 287) were retired, and 23% (66 of 287) were unemployed or on disability. The primary outcome of interest was self-reported PROMIS CAT questionnaire completion grouped as: fully completed, partially completed, or no part completed. Overall, self-reported PROMIS CAT questionnaire completion proportions were: 80% (229 of 287) full completion, 13% (37 of 287) partial completion, and 7% (21 of 287) no part completed. We collected the National Area Deprivation Index (ADI) score and the Brief Health Literacy Screening Tool (BRIEF) as part of the study survey to associate with level of completion. Additionally, patient understanding of PROMIS CAT was assessed through Likert-scaled responses to a study survey question that directly asked whether the patient understood all of the questions on the PROMIS CAT questionnaire. Responses to this question may have been limited by social desirability bias, and hence may overestimate how many individuals genuinely understood the questionnaire content. However, the benefit of this approach was it efficiently allowed us to estimate the ceiling effect of patient comprehension of PROMIS CAT and likely had a high degree of specificity for detecting lack of comprehension. RESULTS: ADI score adjusted for age was not associated with PROMIS CAT completion (partial completion OR 1.00 [95% CI 0.98 to 1.01]; p = 0.72, no part completed OR 1.01 [95% CI 0.99 to 1.03]; p = 0.45). Patients with lower health literacy scores, however, were more likely to not complete any part of their assigned questionnaires than patients with higher scores (no part completed OR 0.85 [95% CI 0.75 to 0.97]; p = 0.02). Additionally, 74% (26 of 35) of patients who did not fully understand all of the PROMIS CAT questionnaire questions still fully completed them-hence, 11% (26 of 229) of all patients who fully completed PROMIS CAT did not fully understand the content. Among patients self-reporting full completion of PROMIS CAT with health literacy data (99% [227 of 229]), patients with inadequate/marginal health literacy were more likely than patients with adequate health literacy to not fully understand all of the questions (21% [14 of 67] versus 8% [12 of 160], OR 3.26 [95% CI 1.42 to 7.49]; p = 0.005). CONCLUSION: Within an urban, socioeconomically diverse, orthopaedic patient population, health literacy was associated with PROMIS CAT questionnaire completion. Lower health literacy levels increased the likelihood of not completing any part of the assigned PROMIS CAT questionnaires. Additionally, patients completed PROMIS CAT without fully understanding the questions. This indicates that patient completion does not guarantee comprehension of the questions nor validity of their scores, even more so among patients with low health literacy. This is a substantive concern for fidelity of data gathered from PROMIS CAT. CLINICAL RELEVANCE: Clinical implementation of the PROMIS CAT in orthopaedic populations will benefit from further research into health literacy to increase questionnaire completion and to ensure that patients understand the content of the questions they are answering, which will increase the internal validity of the outcome measure.

Civilian Ballistic Arthrotomies: Infection Rates and Operative Versus Nonoperative Management.

OBJECTIVES: The purpose of this study was to determine whether a significant difference existed in the rate of infection after ballistic traumatic arthrotomy managed operatively compared with those managed without surgery. DESIGN: Retrospective cohort study. SETTING: Academic Level I Trauma Center. PATIENT SELECTION CRITERIA: Patients with ballistic traumatic arthrotomies of the shoulder, elbow, wrist, hip, knee, or ankle who received operative or nonoperative management. OUTCOME MEASURES AND COMPARISONS: The rates of infection and septic arthritis in those who received operative or nonoperative management. RESULTS: One hundred ninety-five patients were studied. Eighty patients were treated nonoperatively (Non-Op group), 16 patients were treated with formal irrigation and debridement in the operating room (I&D group), and 99 patients were treated with formal I&D and open reduction and internal fixation (ORIF) (I&D + ORIF group). Patients in all 3 groups received local wound care and systemic antibiotics. No patients in the Non-Op or I&D group developed an infection. Six patients in the I&D + ORIF group developed extra-articular postoperative infections requiring additional interventions. CONCLUSIONS: The infection rate in the I&D + ORIF group was consistent with the infection rates reported in orthopaedic literature after fixation alone. In addition, none of the infections were cases of septic arthritis. This suggests that traumatic arthrotomy does not increase the risk for infection beyond what is expected after fixation alone. Importantly, the Non-Op group represented a series of 80 patients who were treated nonoperatively without developing an infection, indicating that I&D may not be necessary to prevent infection after ballistic arthrotomy. The results suggest that septic arthritis after civilian ballistic arthrotomy is a rare complication regardless of the choice of treatment. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Efficacy of Postoperative Radiographs After Intramedullary Nailing of the Tibia and Femur: When Are They Useful?

INTRODUCTION: Postoperative radiographs are used to monitor fractures of the tibia and femur after intramedullary fixation. This study sought to examine how frequently these radiographs change management. METHODS: This was a single-center chart review of patients over a 4-year period at a level I trauma center. Radiographs were defined as either performed for routine surveillance or performed with some clinical correlate on history and examination. Participants received intramedullary nailing for diaphyseal fractures of the femur or tibia. Patients required at least one postoperative radiograph. All patients were subject to our institution's follow-up protocol: visits at 2, 6, 12, and 24 weeks. Radiographs that changed management were those that led to alterations in follow-up, directed counseling, or contributed to the decision to proceed with revision surgery. RESULTS: A total of 374 patients were found. Two hundred seventy-seven received at least one post-op radiograph. The median follow-up was 23 weeks. Six hundred seventeen total radiographs were reviewed. Nine radiographs contributed to a change in management (9/617 = 1.5%). No surveillance radiograph taken before 14 weeks resulted in changes in management. DISCUSSION: Our results suggest that radiographs taken in the first 3 months post-op in asymptomatic patients treated with lower extremity intramedullary rods do not result in changes to clinical management.

Ankle Fractures in Diabetic Patients: A Critical Analysis.

¼: Patients with diabetes are at higher risk for complications after surgical fixation of unstable fractures due to impaired neurovascular functioning and wound-healing capabilities. ¼: Patients with uncontrolled diabetes have higher rates of complications when compared with patients with controlled diabetes. ¼: Despite higher rates of complications, operative fixation of unstable ankle fractures in diabetic patients reliably leads to a functional lower extremity with an overall lower rate of complications than nonoperative management. ¼: Operatively and nonoperatively managed ankle fractures in patients with diabetes should remain non-weight-bearing for an extended period of time. ¼: Discussion of risk of poor outcomes including deep infection, loss of reduction, return to the operating room, and risk of arthrodesis or amputation should be explicitly discussed with patients and families when managing unstable ankle fractures in diabetic patients.

Comparison of a Novel Modified All-Suture Construct versus Suspensory Suture-button Fixation in a Syndesmotic Injury Model.

OBJECTIVES: To biomechanically investigate a novel modified all-suture construct compared with commercially available suspensory button fixation for stabilization of the syndesmosis. METHODS: Eight matched pairs of cadaver lower limbs were obtained. We used a material testing machine and Optotrak optoelectronic 3D motion measurement system for testing. Syndesmotic injuries were simulated, and specimens were fixed with either a suspensory suture button or modified all-suture construct. Repaired specimens were then cyclically loaded for 500 cycles. Spatial relationship of the tibia and fibula were continuously monitored for the intact, destabilized, and repaired states. The results were analyzed using independent samples t test. RESULTS: There was no significant difference in sagittal or coronal plane translation between intact and either repair. Compared with the intact state, both repair techniques demonstrated significantly more external rotation of the fibula relative to the tibia and decreased construct stiffness. Cycling of the specimens did not significantly increase coronal or sagittal plane translation; however, external rotation of the fibula relative to the tibia increased and stiffness decreased with cycling for both repair techniques. CONCLUSIONS: Our data suggest that sagittal and coronal plane translation is no different from the intact state for both fixation techniques. However, rotation of the fibula relative to the tibia was increased, and construct stiffness was decreased compared with the intact state for both fixation techniques. These findings suggest that an all-suture construct could offer syndesmotic fixation comparable with proprietary suspensory button fixation in a cadaver model.

Salvage of Chronic Syndesmosis Instability: A Retrospective Review With Mid-Term Follow-Up.

Malreduced syndesmotic injuries lead to poor outcomes. No consensus exists regarding preferred surgical treatment. This study aims to assess clinical and radiographic outcomes in patients undergoing distal tibiofibular arthrodesis or stabilization. Retrospective review identified patients undergoing distal tibiofibular arthrodesis or stabilization between 2003 and 2019. Surgical factors, revision surgeries, and American Orthopedic Foot and Ankle Score ankle-hindfoot scores were collected. Radiographs were independently evaluated by 4 surgeons. Seventy patients were included. Mean American Orthopedic Foot and Ankle Score scores (n = 33) improved from 48 ± 16 preoperatively to 85 ± 14 (p < .001) at a median follow-up of 31.1 months. Mean Kellgren scores (n = 47) increased from 2.1 ± 1 to 2.5 ± 1 (p < .001) and the mean medial clear space decreased from 3.2 mm ± 0.8 mm to 2.8 mm ± 0.8 mm (p <.001) with no differences between the arthrodesis and stabilization groups. Zero patients progressed to arthroplasty or fusion. Patients demonstrated significant functional improvement after distal tibiofibular arthrodesis and stabilization. Progression of arthritis, while statistically significant, was not clinically significant.

Orthopaedic Management of Gout.

Gout is characterized by the deposition of monosodium urate crystals in patients with chronically elevated blood levels of uric acid. It is the most common form of inflammatory arthritis in the United States and is often comorbid with hypertension, obesity, and chronic kidney disease. Initial presentation is usually an acutely warm, swollen joint, most commonly the first metatarsophalangeal joint, but a variety of locations may be affected. The main treatment for gout is medical management of acute inflammation and chronic uric acid levels, but surgical treatment may be indicated in cases of damage to the surrounding soft tissue, concomitant septic arthritis, symptomatic cartilage loss, or neurologic deficits. Based on the literature to date, gout does not seem to independently affect outcomes after total hip, knee, and ankle arthroplasty, but associated comorbidities affecting outcomes in these patients should be considered.

Diabetic Kidney Disease Is Associated With Increased Complications Following Operative Management of Ankle Fractures.

Background: Diabetes mellitus and peripheral neuropathy are established risk factors for complications in operatively treated ankle fractures. Generally, the presence of peripheral neuropathy and diabetic nephropathy have been used as independent variables in studies of diabetic ankle fracture cohorts but are typically treated as binary risk factors. Our purpose was to quantify the effects of risk factors on complication rate specific to diabetic patients undergoing ankle fracture fixation. Methods: We identified 617 rotational ankle fractures treated operatively at a single academic medical center from 2010 to 2019, of which 160 were identified as diabetic. Of these, 91 ankle fractures in 90 diabetic patients met criteria for retrospective review of clinical and radiographic data. Criteria included perioperative laboratory studies, including glycated hemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR), as well as follow-up radiographs in the electronic record. We defined complications in this surgical cohort as deep surgical site infection, unplanned return to the operating room, and failure of fixation. Logistic regression was performed and odds ratios (ORs) calculated. Results: The overall complication rate was 28.6% (26/91) in this cohort. Median follow-up was 29 weeks (range: 5-520 weeks). Mean perioperative HbA1c in patients who experienced postoperative complications was 7.6% (range: 5.1%-14.2%) compared with 7.8% (range: 5.6%-13.5%) who did not (P = .69). Diabetic patients with chronic kidney disease (eGFR <60 mL/min per body surface area) (OR 5.29, P = .006) and peripheral neuropathy (OR 4.61, P = .003) were at significantly higher risk of all complications compared with diabetic patients without these comorbidities. Of note, we did not find an association between perioperative HbA1c or body mass index and complication rate. Conclusion: Patients with diabetes complicated by chronic kidney disease are at significantly higher risk of complications following operative management of ankle fractures. Our study also corroborated previous reports that within this high-risk cohort, the presence of peripheral neuropathy is a significant risk factor for complications. These sequalae of diabetic disease are manifestations of microvascular disease, glycosylation of soft tissues, and impaired metabolic pathways. Identifying these risk factors in diabetic patients allows for patient-specific risk stratification, education, and management decisions of ankle fractures. Level of Evidence: Level III, retrospective cohort study.

The Effect of Fascia Iliaca Compartment Blockade on Mortality in Patients With Hip Fractures: Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The purpose of this meta-analysis was to determine whether perioperative fascia iliaca compartment blockade (FICB) decreases mortality in patients with hip fracture. METHODS: MEDLINE (PubMed and Ovid platforms), Web of Science, EMBASE, and Cochrane Database of Systemic Reviews were screened for "fascia iliaca compartment block, hip fracture" articles in English, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, from January 1, 2005, to March 1, 2020. All relevant randomized controlled trials and cohort and case-control studies were included for analysis. Relevant article titles were identified, and their corresponding abstracts were independently reviewed by two authors for inclusion. The full-text articles were then obtained for all relevant identified abstracts and assessed for inclusion in the meta-analysis. Conflicts in quality assessment between the two independent reviewers were resolved by a consensus vote of all authors. RESULTS: Study quality was assessed objectively using the Jadad and Newcastle-Ottawa Scale. This meta-analysis was done in accordance with the PRISMA (http://links.lww.com/JAAOS/A731) and QUORUM guidelines. Quantitative synthesis analysis was done using Cochrane Reviews Review Manager (version 5.3). All analyses were completed using random-effects models and comparing the individual effect sizes within each study. DISCUSSION: Management of hip fracture pain with FICB does not markedly decrease short-term mortality. Our findings support the continued use of FICB for the management of hip fractures in geriatric patients and suggest the need for future prospective randomized controlled trials to further determine FICB's effect on short-term and long-term mortality and functional status. LEVEL OF EVIDENCE: Therapeutic level I.

A functional autophagy pathway is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs).

Mesenchymal stem cells (MSCs) are capable of differentiating into bone, cartilage and adipose tissues. We identified BMP9 as the most potent osteoinductive BMP although detailed mechanism underlying BMP9-regulated osteogenesis of MSCs is indeterminate. Emerging evidence indicates that autophagy plays a critical role in regulating bone homeostasis. We investigated the possible role of autophagy in osteogenic differentiation induced by BMP9. We showed that BMP9 upregulated the expression of multiple autophagy-related genes in MSCs. Autophagy inhibitor chloroquine (CQ) inhibited the osteogenic activity induced by BMP9 in MSCs. While overexpression of ATG5 or ATG7 did not enhance osteogenic activity induced by BMP9, silencing Atg5 expression in MSCs effectively diminished BMP9 osteogenic signaling activity and blocked the expression of the osteogenic regulator Runx2 and the late marker osteopontin induced by BMP9. Stem cell implantation study revealed that silencing Atg5 in MSCs profoundly inhibited ectopic bone regeneration and bone matrix mineralization induced by BMP9. Collectively, our results strongly suggest a functional autophagy pathway may play an essential role in regulating osteogenic differentiation induced by BMP9 in MSCs. Thus, restoration of dysregulated autophagic activity in MSCs may be exploited to treat fracture healing, bone defects or osteoporosis.

Development of a simplified and inexpensive RNA depletion method for plasmid DNA purification using size selection magnetic beads (SSMBs).

Plasmid DNA (pDNA) isolation from bacterial cells is one of the most common and critical steps in molecular cloning and biomedical research. Almost all pDNA purification involves disruption of bacteria, removal of membrane lipids, proteins and genomic DNA, purification of pDNA from bulk lysate, and concentration of pDNA for downstream applications. While many liquid-phase and solid-phase pDNA purification methods are used, the final pDNA preparations are usually contaminated with varied degrees of host RNA, which cannot be completely digested by RNase A. To develop a simple, cost-effective, and yet effective method for RNA depletion, we investigated whether commercially available size selection magnetic beads (SSMBs), such as Mag-Bind® TotalPure NGS Kit (or Mag-Bind), can completely deplete bacterial RNA in pDNA preparations. In this proof-of-principle study, we demonstrated that, compared with RNase A digestion and two commercial plasmid affinity purification kits, the SSMB method was highly efficient in depleting contaminating RNA from pDNA minipreps. Gene transfection and bacterial colony formation assays revealed that pDNA purified from SSMB method had superior quality and integrity to pDNA samples cleaned up by RNase A digestion and/or commercial plasmid purification kits. We further demonstrated that the SSMB method completely depleted contaminating RNA in large-scale pDNA samples. Furthermore, the Mag-bind-based SSMB method costs only 5-10% of most commercial plasmid purification kits on a per sample basis. Thus, the reported SSMB method can be a valuable and inexpensive tool for the removal of bacterial RNA for routine pDNA preparations.

Applications of Biocompatible Scaffold Materials in Stem Cell-Based Cartilage Tissue Engineering.

Cartilage, especially articular cartilage, is a unique connective tissue consisting of chondrocytes and cartilage matrix that covers the surface of joints. It plays a critical role in maintaining joint durability and mobility by providing nearly frictionless articulation for mechanical load transmission between joints. Damage to the articular cartilage frequently results from sport-related injuries, systemic diseases, degeneration, trauma, or tumors. Failure to treat impaired cartilage may lead to osteoarthritis, affecting more than 25% of the adult population globally. Articular cartilage has a very low intrinsic self-repair capacity due to the limited proliferative ability of adult chondrocytes, lack of vascularization and innervation, slow matrix turnover, and low supply of progenitor cells. Furthermore, articular chondrocytes are encapsulated in low-nutrient, low-oxygen environment. While cartilage restoration techniques such as osteochondral transplantation, autologous chondrocyte implantation (ACI), and microfracture have been used to repair certain cartilage defects, the clinical outcomes are often mixed and undesirable. Cartilage tissue engineering (CTE) may hold promise to facilitate cartilage repair. Ideally, the prerequisites for successful CTE should include the use of effective chondrogenic factors, an ample supply of chondrogenic progenitors, and the employment of cell-friendly, biocompatible scaffold materials. Significant progress has been made on the above three fronts in past decade, which has been further facilitated by the advent of 3D bio-printing. In this review, we briefly discuss potential sources of chondrogenic progenitors. We then primarily focus on currently available chondrocyte-friendly scaffold materials, along with 3D bioprinting techniques, for their potential roles in effective CTE. It is hoped that this review will serve as a primer to bring cartilage biologists, synthetic chemists, biomechanical engineers, and 3D-bioprinting technologists together to expedite CTE process for eventual clinical applications.

Notch signaling: Its essential roles in bone and craniofacial development.

Notch is a cell-cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.

Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine.

Bone is a dynamic organ with high regenerative potential and provides essential biological functions in the body, such as providing body mobility and protection of internal organs, regulating hematopoietic cell homeostasis, and serving as important mineral reservoir. Bone defects, which can be caused by trauma, cancer and bone disorders, pose formidable public health burdens. Even though autologous bone grafts, allografts, or xenografts have been used clinically, repairing large bone defects remains as a significant clinical challenge. Bone tissue engineering (BTE) emerged as a promising solution to overcome the limitations of autografts and allografts. Ideal bone tissue engineering is to induce bone regeneration through the synergistic integration of biomaterial scaffolds, bone progenitor cells, and bone-forming factors. Successful stem cell-based BTE requires a combination of abundant mesenchymal progenitors with osteogenic potential, suitable biofactors to drive osteogenic differentiation, and cell-friendly scaffold biomaterials. Thus, the crux of BTE lies within the use of cell-friendly biomaterials as scaffolds to overcome extensive bone defects. In this review, we focus on the biocompatibility and cell-friendly features of commonly used scaffold materials, including inorganic compound-based ceramics, natural polymers, synthetic polymers, decellularized extracellular matrix, and in many cases, composite scaffolds using the above existing biomaterials. It is conceivable that combinations of bioactive materials, progenitor cells, growth factors, functionalization techniques, and biomimetic scaffold designs, along with 3D bioprinting technology, will unleash a new era of complex BTE scaffolds tailored to patient-specific applications.

FAMSi: A Synthetic Biology Approach to the Fast Assembly of Multiplex siRNAs for Silencing Gene Expression in Mammalian Cells.

RNA interference (RNAi) is mediated by an ∼21-nt double-stranded small interfering RNA (siRNA) and shows great promise in delineating gene functions and in developing therapeutics for human diseases. However, effective gene silencing usually requires the delivery of multiple siRNAs for a given gene, which is often technically challenging and time-consuming. In this study, by exploiting the type IIS restriction endonuclease-based synthetic biology methodology, we developed the fast assembly of multiplex siRNAs (FAMSi) system. In our proof-of-concept experiments, we demonstrated that multiple fragments containing three, four, or five siRNA sites targeting common Smad4 and/or BMPR-specific Smad1, Smad5, and Smad8 required for BMP9 signaling could be assembled efficiently. The constructed multiplex siRNAs effectively knocked down the expression of Smad4 and/or Smad1, Smad5, and Smad8 in mesenchymal stem cells (MSCs), and they inhibited all aspects of BMP9-induced osteogenic differentiation in bone marrow MSCs (BMSCs), including decreased expression of osteogenic regulators/markers, reduced osteogenic marker alkaline phosphatase (ALP) activity, and diminished in vitro matrix mineralization and in vivo ectopic bone formation. Collectively, we demonstrate that the engineered FAMSi system provides a fast-track platform for assembling multiplexed siRNAs in a single vector, and thus it may be a valuable tool to study gene functions or to develop novel siRNA-based therapeutics.

The new 'normal': Rapid adoption of telemedicine in orthopaedics during the COVID-19 pandemic.

BACKGROUND: Telemedicine provides a safe and effective means for the delivery of care by physicians amongst many subspecialties. Historically, orthopaedic practices in the United States have not widely utilized telemedicine for the delivery of orthopaedic care. As technology improves the adoption and utilization of telemedicine will likely grow, especially in light of the novel coronavirus (COVID-19) pandemic. Our study aims to assess patient and surgeon satisfaction and efficacy of telemedicine during a rapid adoption due to the global pandemic. METHODS: All patients who completed a telemedicine encounter (telephone or video) with an orthopaedic surgeon were contacted. Patients were individually contacted after their visit, and a standardized validated post-visit satisfaction survey was completed. Orthopaedic surgeons completed a standardized post-encounter survey after each visit. Pre-COVID-19 patient satisfaction data was used for comparison. RESULTS: Orthopaedic surgeons completed 612 telehealth encounters either via phone or video consultation between April 6, 2020 and May 22, 2020. 95% of patients rated both surgeon sensitivity to their needs and response to their concerns as 'good' or 'very good.' 93% of patients reported they would participate in a telemedicine encounter again. Surgeons reported high satisfaction with telemedicine encounters (80%, 86% phone and video respectively), and that 78.4% of the time a telemedicine encounter was successful in replacing an in-person visit. CONCLUSION: Patients and orthopaedic surgeons documented high levels of satisfaction with telehealth encounters during the novel coronavirus (COVID-19) pandemic. Telemedicine does not appear to be a replacement for all in-person clinic encounters, however, when used in the appropriate context demonstrated favourable results. LEVEL OF EVIDENCE: Level 4 Study.