Endothelial progenitor cells for diabetic cardiac and kidney disease.

The management of diabetes mellitus and its resultant end organ dysfunction represents a major challenge to global health-care systems. Diabetic cardiac and kidney disease commonly co-occur and are significant contributors to the morbidity and mortality of patients with diabetes, carrying a poor prognosis. The tight link of these parallel end organ manifestations suggests a deeper common underlying pathology. Here, we outline the mechanistic link between diabetic cardiac and kidney disease, providing evidence for the role of endothelial dysfunction in both processes and the potential for cellular therapy to correct these disorders. Specifically, we review the preclinical and clinical evidence for endothelial progenitor cell therapy in cardiac, kidney, and cardio-renal disease applications. Finally, we outline novel approaches to endothelial progenitor cell therapy through cell enhancement and the use of extracellular vesicles, discussing published and future work.

Management of non-union of rib fractures secondary to trauma: A scoping review.

OBJECTIVE: Rib fracture non-union is an uncommon complication of traumatic rib fractures. Our objective was to perform a scoping review of the literature for the management of rib fracture non-union. This included analysis of the variations in surgical technique, complications experienced, and reported outcomes. METHODS: We conducted a scoping review and searched databases (MEDLINE, CINAHL, and Embase). We performed abstract and full-text screening, and abstracted data related to pre-operative assessment, surgical technique, complications, and reported outcome measures. RESULTS: We included 29 articles of which 19 were case reports and 10 were case series. The data quality was generally heterogeneous. The studies included 229 patients and the commonest symptoms of rib fracture non-union included chest pain, clicking, dyspnea and deformities. The patients underwent surgical management of rib fracture non-union (excluding first rib fractures) using various techniques. The majority used surgical stabilization of rib fracture with or without a graft. The reported outcomes were inconsistent between studies, but showed high rates of union (>94 %), reduction in reported VAS scores, and improved return to work when included. Implant failure occurred in 10 % of the 229 total patients reported in our studies, the re-operation rate was 13 %, and the overall complication rate was 27 %. CONCLUSION: Surgical management of rib fracture non-union often involving locking plates and screws with or without a graft has been shown in several case reports and series as an effective treatment with acceptable implant failure and complication rates. Surgical management is therefore a viable option for symptomatic patients. Further research is required to determine optimal management strategies that further reduce surgical complications for these patients.

Distal femur fractures: basic science and international perspectives.

Distal femur fractures are challenging injuries to manage, and complication rates remain high. This article summarizes the international and basic science perspectives regarding distal femoral fractures that were presented at the 2022 Orthopaedic Trauma Association Annual Meeting. We review a number of critical concepts that can be considered to optimize the treatment of these difficult fractures. These include biomechanical considerations for distal femur fixation constructs, emerging treatments to prevent post-traumatic arthritis, both systemic and local biologic treatments to optimize nonunion management, the relative advantages and disadvantages of plate versus nail versus dual-implant constructs, and finally important factors which determine outcomes. A robust understanding of these principles can significantly improve success rates and minimize complications in the treatment of these challenging injuries.

Early Versus Delayed Weight Bearing and Mobilization After Ankle Fracture Fixation Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

The purpose of this review was to determine whether there is a benefit to early weight bearing or mobilization in surgically treated ankle fractures. All randomized controlled trials that analyzed early vs delayed weight bearing and/or mobilization after an ankle surgery were included. The primary outcome measure was the pooled Olerud Molander Ankle Score 1 year postoperatively. No significant differences in ankle function were found at 1 year postoperatively between early and delayed weight bearing and mobilization. The 12-week results demonstrated superior early ankle function scores for patients who had early weight bearing. Patients who had early mobilization were at increased risk for postoperative complications. In surgically treated ankle fractures, early weight bearing resulted in improved short-term ankle function scores. [Orthopedics. 2024;47(2):71-78.].

Optimal delivery of endothelial progenitor cells in a rat model of critical-size bone defects.

Nonunion and segmental bone defects are complex issues in orthopedic trauma. The use of endothelial progenitor cells (EPCs), as part of a cell-based therapy for bone healing is a promising approach. In preclinical studies, culture medium (CM) is commonly used to deliver EPCs to the defect site, which has the potential for immunogenicity in humans. The goal of this study was to find an effective and clinically translatable delivery medium for EPCs. Accordingly, this study compared EPCs delivered in CM, phosphate-buffered saline (PBS), platelet-poor plasma (PPP), and platelet-rich plasma (PRP) in a rat model of femoral critical-size defects. Fischer 344 rats (n = 35) were divided into six groups: EPC+CM, EPC+PBS, EPC+PPP, EPC+PRP, PPP alone, and PRP alone. A 5 mm mid-diaphyseal defect was created in the right femur and stabilized with a miniplate. The defect was filled with a gelatin scaffold impregnated with the corresponding treatment. Radiographic, microcomputed tomography and biomechanical analyses were performed. Overall, regardless of the delivery medium, groups that received EPCs had higher radiographic scores and union rates, higher bone volume, and superior biomechanical properties compared to groups treated with PPP or PRP alone. There were no significant differences in any outcomes between EPC subgroups or between PPP and PRP alone. These results suggest that EPCs are effective in treating segmental defects in a rat model of critical-size defects regardless of the delivery medium used. Consequently, PBS could be the optimal medium for delivering EPCs, given its low cost, ease of preparation, accessibility, noninvasiveness, and nonimmunogenic properties.

Reducing the Burden of Disease Associated With Periprosthetic Fractures: Prevention and the Need for Improved Perioperative Care.

The management of periprosthetic fractures remains challenging and controversial. There continues to be a significant burden of disease and substantial resource implications associated with fractures following total joint arthroplasty. Achieving consensus opinions regarding the prevention and treatment of this problem has important implications given the profound effect on patient outcomes. Multidisciplinary care in the preoperative and postoperative settings is critical, with a specific focus on bone health.

Fixation Strategies for Periprosthetic Fractures With Stable Implants.

The fixation of periprosthetic fractures remains challenging and controversial. It is important to achieve consensus opinions regarding the management of stable periprosthetic fractures with internal fixation. Key strategies to optimize surgical decision making and fixation and manage complications following these difficult injuries are addressed.

The Role of Revision Total Joint Arthroplasty for Periprosthetic Fractures With Unstable Implants.

The management of periprosthetic fractures with unstable prosthetic implants is a challenging and commonly encountered problem. It is important to address the many current issues and controversies regarding the treatment of periprosthetic fractures with revision total joint arthroplasty. Key strategies to optimize surgical decision making around the use of arthroplasty and management of complications following these complex injuries will be addressed.

Management of aseptic nonunions and severe bone defects: let us get this thing healed!

Effective nonunion and bone defect management requires consideration of multiple potential contributing factors including biomechanics, biology, metabolic, and patient factors. This article reviews these factors as well as several potential nonunion or bone defect treatments including bone grafts, bone graft substitutes, the induced membrane technique, and distraction osteogenesis. A summary of these concepts and guidelines for an overall approach to management are also provided.

Great debates in trauma biomechanics.

At the 2021 annual meeting of the Orthopaedic Trauma Association, the Basic Science Focus Forum hosted its first ever debate-style symposium focused on biomechanics and fracture repair. The 3 subjects of debate were "Mechanics versus Biology-Which is 'More Important' to Consider?" "Locked Plate versus Forward Dynamization versus Reverse Dynamization-Which Way Should I Go?" and "Sawbones versus Cadaver Models-What Should I Believe Most?" These debates were held because fracture healing is a highly organized synergistic response between biological factors and the local mechanical environment. Multiple studies have demonstrated that both factors play roles in governing bone healing responses, and the causal relationships between the 2 remain unclear. The lack of clarity in this space has led to a spectrum of research with the common goal of helping surgeons make good decisions. Before reading further, the reader should understand that the questions posed in the debate titles are unanswerable and might represent a false choice. Instead, the reader should appreciate that the debates were held to gain a more thorough understanding of these topics based on the current state of the art of experimental and clinical studies, by using an engaging and thought-provoking format.

Operative vs Nonoperative Treatment of Acute Unstable Chest Wall Injuries: A Randomized Clinical Trial.

Importance: Unstable chest wall injuries have high rates of mortality and morbidity. In the last decade, multiple studies have reported improved outcomes with operative compared with nonoperative treatment. However, to date, an adequately powered, randomized clinical trial to support operative treatment has been lacking. Objective: To compare outcomes of surgical treatment of acute unstable chest wall injuries with nonsurgical management. Design, Setting, and Participants: This was a multicenter, prospective, randomized clinical trial conducted from October 10, 2011, to October 2, 2019, across 15 sites in Canada and the US. Inclusion criteria were patients between the ages of 16 to 85 years with displaced rib fractures with a flail chest or non-flail chest injuries with severe chest wall deformity. Exclusion criteria included patients with significant other injuries that would otherwise require prolonged mechanical ventilation, those medically unfit for surgery, or those who were randomly assigned to study groups after 72 hours of injury. Data were analyzed from March 20, 2019, to March 5, 2021. Interventions: Patients were randomized 1:1 to receive operative treatment with plate and screws or nonoperative treatment. Main Outcomes and Measures: The primary outcome was ventilator-free days (VFDs) in the first 28 days after injury. Secondary outcomes included mortality, length of hospital stay, intensive care unit stay, and rates of complications (pneumonia, ventilator-associated pneumonia, sepsis, tracheostomy). Results: A total of 207 patients were included in the analysis (operative group: 108 patients [52.2%]; mean [SD] age, 52.9 [13.5] years; 81 male [75%]; nonoperative group: 99 patients [47.8%]; mean [SD] age, 53.2 [14.3] years; 75 male [76%]). Mean (SD) VFDs were 22.7 (7.5) days for the operative group and 20.6 (9.7) days for the nonoperative group (mean difference, 2.1 days; 95% CI, -0.3 to 4.5 days; P = .09). Mortality was significantly higher in the nonoperative group (6 [6%]) than in the operative group (0%; P = .01). Rates of complications and length of stay were similar between groups. Subgroup analysis of patients who were mechanically ventilated at the time of randomization demonstrated a mean difference of 2.8 (95% CI, 0.1-5.5) VFDs in favor of operative treatment. Conclusions and Relevance: The findings of this randomized clinical trial suggest that operative treatment of patients with unstable chest wall injuries has modest benefit compared with nonoperative treatment. However, the potential advantage was primarily noted in the subgroup of patients who were ventilated at the time of randomization. No benefit to operative treatment was found in patients who were not ventilated. Trial Registration: ClinicalTrials.gov Identifier: NCT01367951.

Elbow Trauma: An Evidence-Based Approach to Improving Outcomes.

The management of elbow fractures remains difficult and controversial. The failure rate of surgical intervention in elbow fractures remains higher than that seen with other fractures, and there remains significant room for improvement in the care of these injuries. Evidence-based management strategies for elbow fractures and how to prevent and manage complications following elbow fracture surgery have been described.

Augmentation of Fracture Repair: Is Anything Ready for Prime Time?

There continues to be a significant burden of disease associated with the delayed healing of common fractures. Despite a number of trials focused on the augmentation of fracture repair, management remains controversial and evidence regarding cost-effectiveness is lacking. The recent evidence that has challenged traditional thinking regarding management of fracture healing problems will be evaluated.

The induced membrane technique: Optimization of bone grafting in a rat model of segmental bone defect.

INTRODUCTION: The induced membrane technique (IMT) is a two-stage surgical procedure used to treat fracture nonunion and bone defects. Although there is an increasing number of animal studies investigating the IMT, few have examined the outcomes of bone healing after a second stage grafting procedure. This study aimed at comparing two bone grafting procedures, as part of the IMT, in order to establish a rat model providing consistent healing outcomes. METHODS: In male Fischer 344 rats, we created a 5 mm defect in the right femur, stabilized the bone with a plate and screws, and inserted a polymethylmethacrylate spacer into the defect. Four weeks later, the spacer was removed. Bone graft was harvested from a donor rat and placed into the defect, followed by membrane and wound closure. Experiments were conducted in two groups. In group 1 (n = 11), the bone graft contained a variable amount of cortical and cancellous bone, the time from donor euthanasia to grafting was up to 240 min, and one donor rat provided graft for 5-6 recipients. In group 2 (n = 12), we reduced the contribution of cortical bone to the graft, included bone marrow, and kept donor euthanasia to grafting time under 150 min. One donor was used per 3-4 recipients. The volume of graft per recipient and all other elements of the protocol were the same across groups. Bone healing at 12 weeks post grafting was compared radiographically by two orthopaedic surgeons in a blinded fashion, based on union status and a modified Lane & Sandhu score. RESULTS: Healing rates improved from 36.4% in Group 1 to 91.6% in Group 2. There was a significant relationship between the methods and resulting union status (p = 0.004). The odds of achieving full union were significantly higher in group 2 compared to group 1 (odds ratio=19.25, 95% confidence interval [1.77-209.55]; p = 0.009). The average radiographic score was also significantly higher in group 2 (p = 0.005). CONCLUSION: The revised bone grafting method significantly improved the healing outcomes and contributed to establishing a consistent rat model of the IMT. This model can benefit preclinical investigations by allowing for reliable and clinically-relevant comparisons.

The induced membrane technique in animal models: a systematic review.

Objectives: The induced membrane technique (IMT) is a 2-stage surgical approach that has become increasingly popular to manage bone defects. Preclinical investigations have been conducted to better understand and define several aspects of this technique. This review summarizes the literature regarding the IMT performed in animal models and identifies potential future directions. Data Sources: Biosis Citation Index, Ovid Embase, and Ovid MEDLINE databases were searched from inception up to June 23, 2021 for articles related to the IMT. Study Selection: Animal studies involving the use of the IMT for segmental defects in long bones were selected. Only full-length original research articles published in English or French were included. Data Extraction: Two authors extracted the data from the selected studies and a third author verified the accuracy of the information. Data Synthesis: Information concerning the animal model, the surgical procedures, and the outcome measures were recorded for each study and compiled. Conclusions: Forty-seven studies were included in this review. Twenty-nine studies (62%) performed both stages of the technique, but only 8 (17%) reported on radiographic union rates explicitly and 5 (11%) included biomechanical testing. A large proportion of the preclinical literature on the IMT has failed to report on radiographic union as an outcome. While studies reporting membrane properties are valuable, they may not provide information that translates into clinical practice or further clinical research if the ultimate outcome of bony healing is not considered. Future animal studies of the IMT should consider this in their study design.

A Comparison of Acute Complications and Mortality Between Geriatric Knee and Hip Fractures: A Matched Cohort Study.

INTRODUCTION: To compare acute complication and mortality rates for operatively treated, closed, isolated, low-energy geriatric knee fractures (distal femur [DFF] or tibial plateau [TPF]) with hip fractures (HFs). METHODS: This is a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program. We identified all patients ≥ 70 years from 2011 to 2016 who underwent surgery for DFF, TPF, or HF. We recorded patient demographics, functional status, complications, and mortality. We matched DFF:TPF:HF patients on a 1:1:10 ratio based on age, sex, body mass index, baseline functional status, and comorbidity. We used the chi square, Fisher exact, and Mann Whitney U tests to compare unadjusted differences between groups and multivariable logistic regression to compare the risk of complications, readmission, or death while adjusting for relevant covariates. RESULTS: When compared with HF, patients in the DFF and TPF groups had longer length of stay and time to index surgery and were more likely to be discharged home. The rate of deep vein thrombosis was significantly higher in the TPF group (TPF = 3.9%, DFF = 1.3%, and HF = 1.2%, P = 0.005). CONCLUSION: Geriatric knee fractures pose a similar risk of acute complications, mortality, and readmission compared with patients with HF. Future studies investigating strategies to decrease risk in this patient cohort are warranted. LEVEL OF EVIDENCE: Therapeutic Level III.

Operative Versus Nonoperative Treatment of Acute Displaced Distal Clavicle Fractures: A Multicenter Randomized Controlled Trial.

OBJECTIVES: To evaluate the differences in patient outcomes after operative or nonoperative treatment of displaced, type II distal clavicle fractures. DESIGN: Multicenter, prospective, randomized controlled trial. SETTING: Level I trauma centers. PATIENTS/PARTICIPANTS: Patients with completely displaced type II distal clavicle fractures were included. Fifty-seven patients were randomized: 27 to the operative group and 30 to the nonoperative group. INTERVENTION: Patients randomized to nonoperative care received a standard shoulder sling, followed by pendulum or gentle range of motion shoulder exercises at any time as directed by the attending surgeon. Patients randomized to the operative group received plate fixation with a precontoured distal clavicular plate or a "hook" plate within 28 days from injury. MAIN OUTCOME MEASURE: Disabilities of the Arm, Shoulder and Hand scores at 1 year. RESULTS: There were no between-group differences in Disabilities of the Arm, Shoulder and Hand or Constant scores at 1 year. More patients in the operative group went on to union (95% vs. 64%, P = 0.02) within 1 year. Twelve patients in the operative group underwent a second operation for implant removal (12/27, 44%). In the nonoperative group, 6 patients (6/30, 20%) subsequently underwent 8 operative procedures. CONCLUSION: Although this study failed to demonstrate a difference in functional outcomes between operative and nonoperative treatment of Neer type II distal clavicle fractures, nonoperative management led to more complications including a moderate rate of nonunion, which often required secondary surgery to correct, a higher rate of early dissatisfaction with shoulder appearance, and a delayed return to activities in the first 6 months. Operative management provided a safe and reliable treatment option with few complications, but often required secondary implant removal, especially with hook plate fixation. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.