Skin Antisepsis before Surgical Fixation of Extremity Fractures.

BACKGROUND: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). METHODS: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications. RESULTS: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups. CONCLUSIONS: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.).

Using AI to Write a Review Article Examining the Role of the Nervous System on Skeletal Homeostasis and Fracture Healing.

PURPOSE OF REVIEW: Three review articles have been written that discuss the roles of the central and peripheral nervous systems in fracture healing. While content among the articles is overlapping, there is a key difference between them: the use of artificial intelligence (AI). In one paper, the first draft was written solely by humans. In the second paper, the first draft was written solely by AI using ChatGPT 4.0 (AI-only or AIO). In the third paper, the first draft was written using ChatGPT 4.0 but the literature references were supplied from the human-written paper (AI-assisted or AIA). This project was done to evaluate the capacity of AI to conduct scientific writing. Importantly, all manuscripts were fact checked and extensively edited by all co-authors rendering the final manuscript drafts significantly different from the first drafts. RECENT FINDINGS: Unsurprisingly, the use of AI decreased the time spent to write a review. The two AI-written reviews took less time to write than the human-written paper; however, the changes and editing required in all three manuscripts were extensive. The human-written paper was edited the most. On the other hand, the AI-only paper was the most inaccurate with inappropriate reference usage and the AI-assisted paper had the greatest incidence of plagiarism. These findings show that each style of writing presents its own unique set of challenges and advantages. While AI can theoretically write scientific reviews, from these findings, the extent of editing done subsequently, the inaccuracy of the claims it makes, and the plagiarism by AI are all factors to be considered and a primary reason why it may be several years into the future before AI can present itself as a viable alternative for traditional scientific writing.

Role of the Neurologic System in Fracture Healing: An Extensive Review.

PURPOSE OF REVIEW: Despite advances in orthopedics, there remains a need for therapeutics to hasten fracture healing. However, little focus is given to the role the nervous system plays in regulating fracture healing. This paucity of information has led to an incomplete understanding of fracture healing and has limited the development of fracture therapies that integrate the importance of the nervous system. This review seeks to illuminate the integral roles that the nervous system plays in fracture healing. RECENT FINDINGS: Preclinical studies explored several methodologies for ablating peripheral nerves to demonstrate ablation-induced deficits in fracture healing. Conversely, activation of peripheral nerves via the use of dorsal root ganglion electrical stimulation enhanced fracture healing via calcitonin gene related peptide (CGRP). Investigations into TLR-4, TrkB agonists, and nerve growth factor (NGF) expression provide valuable insights into molecular pathways influencing bone mesenchymal stem cells and fracture repair. Finally, there is continued research into the connections between pain and fracture healing with findings suggesting that anti-NGF may be able to block pain without affecting healing. This review underscores the critical roles of the central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (ANS) in fracture healing, emphasizing their influence on bone cells, neuropeptide release, and endochondral ossification. The use of TBI models contributes to understanding neural regulation, though the complex influence of TBI on fracture healing requires further exploration. The review concludes by addressing the neural connection to fracture pain. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair.

PURPOSE OF REVIEW: The traditionally understated role of neural regulation in fracture healing is gaining prominence, as recent findings underscore the peripheral nervous system's critical contribution to bone repair. Indeed, it is becoming more evident that the nervous system modulates every stage of fracture healing, from the onset of inflammation to repair and eventual remodeling. RECENT FINDINGS: Essential to this process are neurotrophins and neuropeptides, such as substance P, calcitonin gene-related peptide, and neuropeptide Y. These molecules fulfill key roles in promoting osteogenesis, influencing inflammation, and mediating pain. The sympathetic nervous system also plays an important role in the healing process: while local sympathectomies may improve fracture healing, systemic sympathetic denervation impairs fracture healing. Furthermore, chronic activation of the sympathetic nervous system, often triggered by stress, is a potential impediment to effective fracture healing, marking an important area for further investigation. The potential to manipulate aspects of the nervous system offers promising therapeutic possibilities for improving outcomes in fracture healing. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Do Not Lose Your Nerve, Be Callus: Insights Into Neural Regulation of Fracture Healing.

PURPOSE OF REVIEW: Fractures are a prominent form of traumatic injury and shall continue to be for the foreseeable future. While the inflammatory response and the cells of the bone marrow microenvironment play significant roles in fracture healing, the nervous system is also an important player in regulating bone healing. RECENT FINDINGS: Considerable evidence demonstrates a role for nervous system regulation of fracture healing in a setting of traumatic injury to the brain. Although many of the impacts of the nervous system on fracture healing are positive, pain mediated by the nervous system can have detrimental effects on mobilization and quality of life. Understanding the role the nervous system plays in fracture healing is vital to understanding fracture healing as a whole and improving quality of life post-injury. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Clinical Assessments of Fracture Healing and Basic Science Correlates: Is There Room for Convergence?

PURPOSE OF REVIEW: The purpose of this review is to summarize the clinical and basic science methods used to assess fracture healing and propose a framework to improve the translational possibilities. RECENT FINDINGS: Mainstays of fracture healing assessment include clinical examination, various imaging modalities, and assessment of function. Pre-clinical studies have yielded insight into biomechanical progression as well as the genetic, molecular, and cellular processes of fracture healing. Efforts are emerging to identify early markers to predict impaired healing and possibly early intervention to alter these processes. Despite of the differences in clinical and preclinical research, opportunities exist to unify and improve the translational efforts between these arenas to develop and optimize our ability to assess and predict fracture healing, thereby improving the clinical care of these patients.

Outcomes Following Intramedullary Nailing of Select Periarticular Distal Tibia Fractures.

Intramedullary nailing (IMN) of periarticular distal tibia fractures may offer advantages compared to plating. This study aims to report on the outcomes of select periarticular distal tibia fractures treated with IMN. Patients over 17 years of age that underwent IMN for extraarticular distal tibia fractures (Osteosynthesefragen/Orthopaedic Trauma Association [AO/OTA] 43-A), partial articular with associated segmental shaft component (43-B), and simple intraarticular (43-C1/2) at a Level I trauma center were included. The primary outcome was physical function (PF) and pain interference (PI) assessed via Patient-Reported Outcomes Measurement Information System (PROMIS). Secondary outcomes included reoperation, nonunion, infection, and malalignment. Eighty-four patients with > 12 months follow up were included. Mean PROMIS PI and PF scores were 55.5 and 45.0, respectively. The rate of nonunion and deep infection each were 8%. Eighty-four percent of patients achieved normal alignment. There were no differences detected in clinical outcomes between patients with intraarticular injuries compared with those with extraarticular fractures. Satisfactory clinical, radiographic, and patient-reported outcomes can be expected following treatment of extraarticular and simple intraarticular distal tibia fractures with IMN. (Journal of Surgical Orthopaedic Advances 32(4):246-251, 2023).

Halicin Is Effective Against Staphylococcus aureus Biofilms In Vitro.

BACKGROUND: Biofilms protect bacteria from the host immune system and many antibiotics, making the treatment of orthopaedic infections difficult. Halicin, a recently discovered antibiotic, has potent activity against nonorthopaedic infections in mice and the planktonic, free-living forms of many bacterial species, including Staphylococcus aureus , a common cause of orthopaedic infections. Importantly, halicin did not induce resistance in vitro and was effective against drug-resistant bacteria and proliferating and quiescent bacteria. Quiescence is an important cause of antibiotic tolerance in biofilms. However, whether halicin acts on biofilms has not been tested. QUESTIONS/PURPOSES: (1) Does halicin reduce the viability of S. aureus in less mature and more mature biofilms as it does in planktonic cultures? (2) How do the relative effects of halicin on S. aureus biofilms and planktonic cultures compare with those of conventional antibiotics (tobramycin, cefazolin, vancomycin, or rifampicin) that are commonly used in clinical orthopaedic infections? METHODS: To measure minimal biofilm eradication concentrations (MBECs) with less mature 3-day and more mature 7-day biofilms, we used 96-well peg plates that provided high throughput and excellent reproducibility. After S. aureus -Xen36 biofilm formation, planktonic bacteria were removed from the cultures, and the biofilms were exposed to various concentrations of halicin, tobramycin, cefazolin, vancomycin, or rifampicin for 20 hours. Biofilm viability was determined by measuring resazurin reduction or by counting colony-forming units after sonication. To determine effects of halicin and the conventional antibiotics on biofilm viability, we defined MBEC 75 as the lowest concentration that decreased viability by 75% or more. To determine effects on bacterial viability in planktonic cultures, minimum inhibitory concentrations (MICs) were determined with the broth dilution method. Each result was measured in four to 10 independent experiments. RESULTS: We found no differences between halicin's effectiveness against planktonic S. aureus and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 25 µM [interquartile range 25 to 25 and 25 to 25, respectively]; p > 0.99). Halicin was eightfold less effective against more mature 7-day biofilms (MBEC 75 = 200 µM [100 to 200]; p < 0.001). Similarly, tobramycin was equally effective against planktonic culture and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 20 µM [20 to 20 and 10 to 20, respectively]; p > 0.99). Tobramycin's MBEC 75 against more mature 7-day biofilms was 320 µM (320 to 480), which is 16-fold greater than its planktonic MIC (p = 0.03). In contrast, the MBEC 75 for cefazolin, vancomycin, and rifampicin against more mature 7-day biofilms were more than 1000-fold (> 1000; p < 0.001), 500-fold (500 to 875; p < 0.001), and 3125-fold (3125 to 5469; p = 0.004) greater than their planktonic MICs, respectively, consistent with those antibiotics' relative inactivity against biofilms. CONCLUSION: Halicin was as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but eightfold higher concentrations were needed for more mature 7-day biofilms. Tobramycin, an antibiotic whose effectiveness depends on biofilm maturity, was also as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but 16-fold higher concentrations were needed for more mature 7-day biofilms. In contrast, cefazolin, vancomycin, and rifampicin were substantially less active against both less and more mature biofilms than against planktonic cultures. CLINICAL RELEVANCE: Halicin is a promising antibiotic that may be effective against S. aureus osteomyelitis and infections on orthopaedic implants. Future studies should assess the translational value of halicin by testing its effects in animal models of orthopaedic infections; on the biofilms of other bacterial species, including multidrug-resistant bacteria; and in combination therapy with conventional antibiotics.

Predicting fracture healing with blood biomarkers: the potential to assess patient risk of fracture nonunion.

Fracture non-union is a significant orthopaedic problem affecting a substantial number of patients yearly. Treatment of nonunions is devastating to patients and costly to the healthcare system. Unfortunately, the diagnosis of non-union is typically made in a reactionary fashion by an orthopaedic surgeon based on clinical assessment and radiographic features several months into treatment. For this reason, investigators have been trying to develop prediction algorithms; however, these have relied on population-based approaches and lack the predictive capability necessary to make individual treatment decisions. There is also a growing body of literature focussed on identifying blood biomarkers that are associated with non-union. This review describes the research that has been done in this area. Further studies of patient-centered, precision medicine approaches will likely improve fracture non-union diagnostic/prognostic capabilities.

Intramedullary Nail Fixation of Intra-articular and Extra-articular Proximal Tibia Fractures.

Recent studies suggest advantages to intramedullary nailing (IMN) of extra-articular proximal tibia fractures compared to plating. To our knowledge, no studies have evaluated IMN treatment of proximal tibia fractures with simple articular extension. We sought to compare rate of reoperation, malalignment, and patient-reported outcomes in patients with intra-articular versus extra-articular proximal tibia fractures treated via IMN. This retrospective cohort study compared patients that underwent IMN of extra-articular proximal tibia fractures (AO/OTA 41A2 and A3; n = 33) to simple intra-articular fractures (AO/OTA 41C1 and C2; n = 20) with minimum 12-month follow-up. With the numbers available, no significant differences were detected between the extra- and intra-articular groups for unplanned reoperation (9/33 vs. 2/20, p = 0.18), infection (4/33 vs. 1/20, p = 0.64), nonunion (4/33 vs. 2/20, p > 0.99), or malunion (5/30 vs. 3/19, p > 0.99). IMN of simple intra-articular proximal tibial fractures is a reasonable treatment strategy that may be desirable in certain clinical situations. (Journal of Surgical Orthopaedic Advances 30(1):055-060, 2021).

Retrograde intramedullary nailing below a hip arthroplasty prosthesis: a viable fixation option for periprosthetic and interprosthetic femur fractures.

BACKGROUND: Periprosthetic femur fractures (PPFF) distal to a femoral stem are traditionally treated with open reduction and internal fixation (ORIF) with plate and screws. To our knowledge, no studies exist comparing outcomes following ORIF vs retrograde intramedullary nails (RIMN) for this injury. METHODS: This is a retrospective comparison of PPFFs distal to a femoral stem treated by ORIF (n = 17) vs RIMN (n = 13). The primary outcome was unplanned re-operation. RESULTS: There was no difference in unplanned re-operation (17.6 vs 23.1%, p > 0.99), infection, nonunion, refracture, and alignment between groups. The RIMN group had shorter surgical time (89 vs 157 min, p < 0.01), less blood loss (137 vs 291 ml, p = 0.03), and greater obesity. CONCLUSION: RIMN is a potential option for operative fixation of PPFF distal to a femoral stem worthy of additional study.

Total Knee Arthroplasty in Patients with Blount Disease or Blount-Like Deformity.

Blount disease is associated with complex deformity of the proximal tibia, and some patients will develop knee osteoarthritis. Five patients (eight knees) with Blount disease or Blount-like deformity underwent total knee arthroplasty. Mean proximal tibial metaphyseal-diaphyseal angle was 20.75°. Each patient had substantial posteromedial tibial bony defects and six knees required extensive medial releases. Two knees required increased constraint at index procedure. One patient has undergone bilateral revision surgery with rotating hinge prostheses. Mean WOMAC scores were 13.5 and Knee Society scores were 212.5 at average 75.2 month follow-up. Despite technical challenges, patients with these deformities can have successful outcomes after total knee arthroplasty. Surgeons should be prepared to address posteromedial tibial bony defects and consider constrained arthroplasty at the index procedure.

Irreducible ankle fracture-dislocation due to tibialis anterior subluxation: a case report.

Irreducible ankle fracture-dislocations are rare. Several cases of irreducible ankle fracture-dislocation have been reported in published studies secondary to the tibialis posterior tendon, deltoid ligament, or extensor digitorum longus tendon blocking the reduction. We report a case of irreducible ankle fracture-dislocation resulting from posteromedial subluxation of the tibialis anterior tendon around a medial malleolar fracture fragment. Ultimately, the ankle required open reduction of the incarcerated tendon to reduce the joint and proceed with internal fixation of the associated fracture. The patient's postoperative course was uncomplicated, and the tibialis anterior tendon was functioning at 10 months postoperatively, after which he did not return for follow-up examinations. To our knowledge, this is the first reported case of the tibialis anterior tendon blocking closed reduction of an ankle fracture-dislocation.

Fracture-related infection blood-based biomarkers: Diagnostic strategies.

Fracture-related infections are significant postoperative complications that carry substantial patient burden and additional healthcare costs. Despite their impact on outcome, early diagnosis of these infections remains challenging due to current available tests lacking acceptable diagnostic parameters. This review compiles existing information on blood-based biomarkers that have been evaluated as early diagnostic tools and highlights the challenges in their reliability. To begin to overcome these challenges new avenues of biomarker discovery utilizing "omics" technologies and novel analytical methods are being investigated in recent years. It appears that, despite their complexity, these newer approaches may be the future in biomarker discovery for fracture-related infection diagnosis.

External Fixation Before Planned Conversion to Internal Fixation in Orthopaedic Trauma: Controversies and Current Trends.

External fixation is a widely used technique for a myriad of bone fractures and pathologies in all extremities. Despite its widespread use, controversies and unknowns still exist. This review article seeks to discuss current literature surrounding pin insertion technique, pin-site care, intraoperative use during conversion to definitive fixation, the relationship of pin sites to definitive fixation, and pin-site management after removal for temporary external fixation.

A Novel Use of a Schanz Pin-Rectal Foreign Body Extraction: A Case Report.

Introduction: Retained rectal foreign bodies (RFBs) can be difficult to extract, forcing the surgeon to get creative. This is the first case report utilizing orthopedic drilling and joystick manipulation techniques for foreign body extraction. Case Report: A 63-year-old male presented to the emergency department with a pool ball in his rectum for two days. Extraction attempts under anesthesia both transanally and through a low midline laparotomy were unsuccessful due to the patient's pelvic anatomy. Orthopedic surgery was consulted to see if any manipulation or resection of the pelvis might aid in extraction. Ultimately, a Schanz pin was drilled retrogradely from the rectum into the pool ball and successfully manipulated the pool ball out of the patient. Conclusion: Techniques such as drilling and joystick manipulation are common in orthopedic surgery but rarely used in other surgical fields. This case presented a novel use of a Schanz pin in RFB extraction. Application of orthopedic surgical technique in a colorectal surgery in this case saved the patient from more invasive interventions such as pubic symphysiotomy or ischial tuberosity resection.

Plating Versus Intramedullary Nailing of OTA/AO 43C1 and C2 Intra-articular Distal Tibia Fractures: A Propensity Score and Multivariate Analysis.

OBJECTIVE: To compare rates of reduction loss, nonunion, and infection in intra-articular distal tibia fractures (IADTF) treated with limited open reduction internal fixation and intramedullary nailing (IMN) as compared to open reduction internal fixation with plate and screws (plate fixation [PF]). DESIGN: Retrospective review. SETTING: Level-I academic trauma center. PATIENT SELECTION CRITERIA: Patients age ≥ 18 with OTA/AO 43C1 and C2 IADTF treated with IMN or PF between 2013-2021. OUTCOME MEASURES AND COMPARISONS: Loss of reduction, surgical site infection (SSI), nonunion, and patient-reported outcomes (PROs) were compared for IMN versus PF treatments. RESULTS: One hundred ten patients met the inclusion criteria (IMN 33 and PF 77). There was no loss of reduction found. Seventeen nonunions (15% overall; IMN 4/33 and PF 13/77) and 13 SSIs (12% overall; IMN 2/33 and PF11/77) were identified. Despite several risk factors being identified for nonunion and SSI in bivariate analysis, only open fracture remained significant as a risk factor for both nonunion (odds ratio 0.09 for closed fracture, 95% confidence interval, 0.02-0.56, P = 0.009) and SSI (odds ratio 0.07 for closed fracture, 95% confidence interval, 0.06-0.26, P = 0.012) in the multivariate model. Propensity scoring based on presurgical variables was significantly different between patients who received IMN versus PF ( P = 0.03); however, logistic regression incorporating the propensity score revealed no significant association with nonunion and SSI. Adjusting for the propensity score, there remained no association comparing IMN versus PF with nonunion and SSI ( P = 0.54 and P = 0.17, respectively). There was also no difference in PROs between IMN and PF (physical function: P = 0.25 and pain interference: P = 0.21). CONCLUSIONS: Overall nonunion and SSI prevalence was 15% and 12%, respectively, in operatively treated OTA/AO 43C1 and C2 IADTF. An open fracture was a significant risk factor for nonunion and SSI. Metaphyseal fixation through IMN or PF did not affect loss of reduction, nonunion, SSI, or PROs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A Scoring System for Predicting Nonunion After Intramedullary Nailing of Femoral Shaft Fractures.

INTRODUCTION: Femoral shaft nonunion negatively affects patient quality of life. Although multiple risk factors have been identified for femoral shaft nonunion after intramedullary nail (IMN) fixation, there is no quantitative model for predicting nonunion. STUDY DESCRIPTION: The study is a retrospective cohort study of patients with femoral shaft fractures treated at two level one trauma centers who were followed to fracture union or nonunion. Patient, injury, and surgical characteristics were analyzed to create a quantitative model for nonunion risk after intramedullary nailing. METHODS: Eight hundred one patients aged 18 years and older with femoral shaft fractures treated with reamed, locked IMNs were identified. Risk factors including demographics, comorbidities, surgical variables, and injury-related characteristics were evaluated. Multivariate analysis was conducted, and several variables were included in a scoring system to predict nonunion risk. RESULTS: The overall nonunion rate was 7.62% (61/801). Multivariate analysis showed significant association among pulmonary injury (odds ratio [OR] = 2.19, P = 0.022), open fracture (OR=2.36, P = 0.02), current smoking (OR=3.05, P < 0.001), postoperative infection (OR=12.1, P = 0.007), AO/OTA fracture pattern type A or B (OR=0.43, P = 0.014), and percent cortical contact obtained intraoperatively ≥25% (OR=0.41, P = 0.021) and nonunion. The scoring system created to quantitatively stratify nonunion risk showed that a score of 3 or more yielded an OR of 6.38 for nonunion (c-statistic = 0.693, P < 0.0001). CONCLUSIONS: Femoral shaft nonunion risk is quantifiable based on several independent injury, patient, and surgical factors. This scoring system is an additional tool for clinical decision making when caring for patients with femoral shaft fractures treated with IMNs.

Early Treatment of Acetabular Fractures Using an Anterior Approach Increases Blood Loss but not Packed Red Blood Cell Transfusion.

OBJECTIVE: The objective of this study was to determine whether time from hospital admission to surgery for acetabular fractures using an anterior intrapelvic (AIP) approach affected blood loss. DESIGN: Retrospective review. SETTING: Three level 1 trauma centers at 2 academic institutions. PATIENT SELECTION CRITERIA: Adult (18 years or older) patients with no pre-existing coagulopathy treated for an acetabular fracture via an AIP approach. Excluded were those with other significant same day procedures (irrigation and debridement and external fixation were the only other allowed procedures). OUTCOME MEASURES AND COMPARISONS: Multiple methods for evaluating blood loss were investigated, including estimated blood loss (EBL), calculated blood loss (CBL) by Gross and Hgb balance methods, and packed red blood cell (PRBC) transfusion requirement. Outcomes were evaluated based on time to surgery. RESULTS: 195 patients were studied. On continuous linear analysis, increasing time from admission to surgery was significantly associated with decreasing CBL at 24 hours (-1.45 mL per hour by Gross method, P = 0.003; -0.440 g of Hgb per hour by Hgb balance method, P = 0.003) and 3 days (-1.69 mL per hour by Gross method, P = 0.013; -0.497 g of Hgb per hour by Hgb balance method, P = 0.010) postoperative, but not EBL or PRBC transfusion. Using 48 hours from admission to surgery to define early versus delayed surgery, CBL was significantly greater in the early group compared to the delayed group (453 [IQR 277-733] mL early versus 364 [IQR 160-661] delayed by Gross method, P = 0.017; 165 [IQR 99-249] g of Hgb early versus 143 [IQR 55-238] g Hgb delayed by Hgb balance method, P = 0.035), but not EBL or PRBC transfusion. In addition, in multivariate linear regression, neither giving tranexamic acid nor administering prophylactic anticoagulation for venous thromboembolism on the morning of surgery affected blood loss at 24 hours or 3 days postoperative ( P > 0.05). CONCLUSION: There was higher blood loss with early surgery using an AIP approach, but early surgery did not affect PRBC transfusion and may not be clinically relevant. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Halicin remains active against Staphylococcus aureus in biofilms grown on orthopaedically relevant substrates.

Aims: Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods: S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results: Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion: Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection.