Standard of care and outcomes for Maori patients with neck of femur fractures - an Australia & New Zealand Hip Fracture Registry (ANZHFR) study.

BACKGROUND: This study aimed to compare the demographic differences between Maori and NZ Europeans with neck of femur fracture (NOF), identify any differences in management, surgical and post-op care and outcomes. METHODS: All cases in New Zealand between 2018 and 2020 were collected from the Australia & New Zealand Hip Fracture Registry (ANZHFR). Basic demographics, management factors, and surgical factors were collected. Key outcomes at 120 days post-fracture included walking status, residential status and survival. Univariate analysis was performed to compare differences in demographics, and management factors between ethnicities. Multivariable analysis was conducted on key outcome comparisons and management differences. RESULTS: Data from 9432 patients were analyzed. 305 patients were Maori (3.2%). Age-standardized incidence between Maori and NZ European were similar (103 (95% CI 91-115) vs. 95 (95% CI 92-99)/100 000/year). Maori had a longer time to theatre (38.7 vs. 34.5 h, P = 0.01). The only difference between Maori and NZ European in the key outcomes was private residential status (67% vs. 62% P < 0.01). There was no difference in survival (87% vs. 87% P = 0.68) and decrease in walking status (0.43 vs. 0.41 P = 0.99). Following multivariable analysis, Maori ethnicity was an independent risk factor for time to theatre >48 hours after adjustment for other factors (OR 1.44 (95% CI 1.07, 1.93), P = 0.016). DISCUSSION: Although Maori were a small percentage of patients with NOFs, there was similar age-standardized incidence compared to NZ Europeans. While there were no differences in key outcomes, identifying reasons for longer time to theatre for Maori patients is required.

The Safety of Volar to Dorsal Percutaneous Screw Fixation of Bennett Fracture-Dislocation - A Cadaveric Study.

Background: Bennett fractures are traditionally fixed with percutaneous K-wires from dorsal to volar, or with a volar to dorsal screw via a volar open approach. While volar to dorsal screw fixation is biomechanically advantageous, an open approach requires extensive soft tissue dissection, thus increasing morbidity. This study aims to investigate the practicality and safety of Bennett fracture fixation using a percutaneous, volar to dorsal screw, particularly with regard to the median nerve and its motor branch during wire and screw insertion. Methods: Fifteen fresh frozen forearm and hand specimens were obtained from the University of Auckland human cadaver laboratory. A guidewire is placed under image intensifier from volar to dorsal with the thumb held in traction, abduction and pronation. The wire is passed through the skin volarly under image intensifier, then the median nerve is dissected from the carpal tunnel and the motor branch of the median nerve (MBMN) is dissected from its origin to where it supplies the thenar musculature. The distance between the K-wire to the MBMN is measured. Results: In 14 of 15 specimens, the wire was superficial and radial to the carpal tunnel. The mean distance to the origin of the MBMN is 6.2 mm (95% CI 4.1-8.3) with the closest specimen 1 mm away. The mean closest distance the wire gets to any part of the MBMN is 3.7 mm (95% CI 1.6-5.8); in two specimens, the wire was through the MBMN. Conclusions: Wire placement, although done under image intensifier, is subject to significant variation in exiting location. While research has shown the thenar portal in arthroscopic thumb surgery is safe, our guidewire needs to exit further ulnar to capture the Bennett fracture fragment, placing the MBMN at risk. This cadaveric study has demonstrated the proposed technique is unsafe for use.

Quality Assessment of Degenerative Cervical Myelopathy Information on the Internet.

BACKGROUND: Patient education is a key element of spinal surgery informed consent. Patients frequently access health information online, yet this information is unregulated and of variable quality. We aimed to assess the quality of information available on degenerative cervical myelopathy (DCM) websites with a focus on identifying high-quality information websites. METHODS: We performed a Google search using keywords pertaining to DCM. The top 50 websites returned were classified based on their publication source, intended audience, and country of origin. The quality of these websites was assessed using both the DISCERN instrument and Journal of the American Medical Association (JAMA) benchmark criteria. We also utilized a novel Myelopathy Information Scoring Tool (MIST) to assess the comprehensiveness, accuracy, and detail of online DCM information. RESULTS: The mean DISCERN score was 39.9 out of 80. Only one-quarter of these websites were rated "good" or "excellent" using DISCERN, and the remaining were rated "very poor," "poor," and "fair." The mean JAMA benchmark score was 1.6 out of 4, with 23 out of 50 websites scoring 0. Evaluation using MIST found a mean score of 25.6 out of 50. Using 30 points as a satisfactory MIST cutoff, 72% of DCM websites were deemed critically deficient and unsatisfactory for comprehensive patient education. Both DISCERN and MIST indicated poorest information pertaining to surgical risks and complications as well as treatment outcomes. Websites such as Orthoinfo.aaos.org and Myelopathy.org provided reliable, trustworthy, and comprehensive patient education. CONCLUSIONS: Information available on almost three-quarters of DCM websites was of poor quality, with information regarding complications and treatment outcomes most deficient. Clinicians should be aware of quality sites where patients may be directed to augment patient education and surgical counseling.

Combined Growth Factor Hydrogel Enhances Rotator Cuff Enthesis Healing in Rat But Not Sheep Model.

We hypothesized that a combined growth factor hydrogel would improve chronic rotator cuff tear healing in a rat and sheep model. Insulin-like growth factor 1, transforming growth factor ß1, and parathyroid hormone were combined into a tyraminated poly-vinyl-alcohol (PVA-Tyr) hydrogel and applied directly at the enthesis. In total, 30 Sprague-Dawley rats and 16 Romney ewes underwent unilateral rotator cuff tenotomy and then delayed repairs were performed after 3-4 weeks. The animals were divided into a control group (repair alone) and treatment group. The rotator cuffs were harvested at 12 weeks after surgery for biomechanical and histological analyses of the repair site. In the rat model, the stress at failure and Young's modulus were higher in the treatment group in comparison with the control group (73% improvement, p = 0.010 and 56% improvement, p = 0.028, respectively). Histologically, the repaired entheses in the treatment group demonstrated improved healing with higher semi-quantitative scores (10.1 vs. 6.55 of 15, p = 0.032). In the large animal model, there was no observable treatment effect. This PVA-Tyr bound growth factor system holds promise for improving rotator cuff healing. However, our approach was not scalable from a small to a large animal model. Further tailoring of this growth factor delivery system is still required. Level of Evidence: Basic Science Study; Biomechanics and Histology; Animal Model Impact Statement Previous studies using single-growth factor treatment to improve enthesis healing after rotator cuff repair have reported promising, but inconsistent results. A novel approach is to combine multiple growth factors using controlled-release hydrogels that mimic the normal healing process. In this study, we report that a combined growth factor hydrogel can improve the histological quality and strength of rotator cuff repair in a rat chronic tear model. This novel hydrogel growth factor treatment has the potential to be used in human clinical applications to improve healing after rotator cuff repair.

Success of Debridement, Antibiotics, and Implant Retention in Prosthetic Joint Infection Following Primary Total Knee Arthroplasty: Results From a Prospective Multicenter Study of 189 Cases.

BACKGROUND: This study aimed to identify the success rate of debridement, antibiotics, and implant retention (DAIR) for prosthetic joint infection (PJI) in a large prospective cohort of patients undergoing total knee arthroplasty (TKA). The ability for different PJI classification systems to predict success was assessed. METHODS: Prospective data recorded in the Prosthetic Joint Infection in Australia and New Zealand Observational study were analyzed. One hundred eighty-nine newly diagnosed knee PJIs were managed with DAIR between July 2014 and December 2017. Patients were prospectively followed up for 2 years. A strict definition of success was used, requiring the patient being alive with documented absence of infection, no ongoing antibiotics and the index prosthesis in place. Success was compared against the Coventry (early PJI ≤1 month), International Consensus Meeting (early ≤90 days), Auckland (early <1 year), and Tsukayama (early ≤1 month, hematogenous >1 month with <7 days symptoms, chronic >1 month with >7 days symptoms) classifications. RESULTS: DAIR success was 45% (85/189) and was highest in early PJIs defined according to the Coventry (adjusted odds ratio [aOR] = 3.9, P = .01), the International Consensus Meeting (aOR = 3.1, P = .01), and the Auckland classifications (aOR = 2.6, P = .01). Success was lower in both hematogenous (aOR = 0.4, P = .03) and chronic infections (aOR = 0.1, P = .003). CONCLUSION: Time since primary TKA is an important predictor of DAIR success. Success was highest in infections occurring <1 month of the primary TKA and progressively decreased as time since the primary TKA increased.

Comparing modern uncemented, hybrid and cemented implant combinations in older patients undergoing primary total hip arthroplasty, a New Zealand Joint Registry study.

BACKGROUND: Multiple joint registries have reported better implant survival for patients aged > 75 years undergoing total hip arthroplasty (THA) with cemented implant combinations when compared to hybrid or uncemented implant combinations. However, there is considerable variation within these broad implant categories, and it has therefore been suggested that specific implant combinations should be compared. We analysed the most common contemporary uncemented (Corail/Pinnacle), hybrid (Exeter V40/Trident) and cemented (Exeter V40/Exeter X3) implant combinations in the New Zealand Joint Registry (NZJR) for patients aged > 75 years. METHODS: All THAs performed using the selected implants in the NZJR for patients aged > 75 years between 1999 and 2018 were included. Demographic data, implant type, and outcome data including implant survival, reason for revision, and post-operative Oxford Hip Scores were obtained from the NZJR, and detailed survival analyses were performed. Primary outcome was revision for any reason. Reason for revision, including femoral or acetabular failure, and time to revision were recorded. RESULTS: 5427 THAs were included. There were 1105 implantations in the uncemented implant combination group, 3040 in the hybrid implant combination group and 1282 in the cemented implant combination group. Patient reported outcomes were comparable across all groups. Revision rates were comparable between the cemented implant combination (0.31 revisions/100 component years) and the hybrid implant combination (0.40 revisions/100 component years) but were statistically significantly higher in the uncemented implant combination (0.80/100 component years). Femoral-sided revisions were significantly greater in the uncemented implant combination group. CONCLUSION: The cemented implant and hybrid implant combinations provide equivalent survival and functional outcomes in patients aged over 75 years. Caution is advised if considering use of the uncemented implant combination in this age group, predominantly due to a higher risk of femoral-sided revisions. The authors recommend comparison of individual implants rather than broad categories of implants.

Machine learning for the prediction of minor amputation in University of Texas grade 3 diabetic foot ulcers.

Minor amputations are performed in a large proportion of patients with diabetic foot ulcers (DFU) and early identification of the outcome of minor amputations facilitates medical decision-making and ultimately reduces major amputations and deaths. However, there are currently no clinical predictive tools for minor amputations in patients with DFU. We aim to establish a predictive model based on machine learning to quickly identify patients requiring minor amputation among newly admitted patients with DFU. Overall, 362 cases with University of Texas grade (UT) 3 DFU were screened from tertiary care hospitals in East China. We utilized the synthetic minority oversampling strategy to compensate for the disparity in the initial dataset. A univariable analysis revealed nine variables to be included in the model: random blood glucose, years with diabetes, cardiovascular diseases, peripheral arterial diseases, DFU history, smoking history, albumin, creatinine, and C-reactive protein. Then, risk prediction models based on five machine learning algorithms: decision tree, random forest, logistic regression, support vector machine, and extreme gradient boosting (XGBoost) were independently developed with these variables. After evaluation, XGBoost earned the highest score (accuracy 0.814, precision 0.846, recall 0.767, F1-score 0.805, and AUC 0.881). For convenience, a web-based calculator based on our data and the XGBoost algorithm was established (https://dfuprediction.azurewebsites.net/). These findings imply that XGBoost can be used to develop a reliable prediction model for minor amputations in patients with UT3 DFU, and that our online calculator will make it easier for clinicians to assess the risk of minor amputations and make proactive decisions.

Optimal Graft Choice in Athletic Patients with Anterior Cruciate Ligament Injuries: Review and Clinical Insights.

Anterior cruciate ligament (ACL) rupture is a common sporting-related knee injury with a potentially detrimental impact on the athlete's career, yet there is no formal consensus on the optimal graft choice for reconstructing the ruptured ACL in this specific population. Options for reconstruction include autograft, allograft, and artificial grafts. However, each has associated failure risk and donor site morbidity. Our operational definition of the athlete is a skeletally mature individual participating in high level activity with the expectation to return to pre-injury level of activity. The athlete has unique injury characteristics, post-operative expectations, and graft demands that differ to the general population. Long-term outcomes are of particular importance given on-going mechanical demands on the reconstructed knee. Therefore, the purpose of this review is to consolidate current literature on the various ACL reconstruction graft options, with a focus on the optimal graft for returning the athlete to activity with the lowest rate of re-injury.

Tibial metaphyseal cones combined with short stems perform as well as long stems in revision total knee arthroplasty.

BACKGROUNDS: There is uncertainty around optimal tibial stem length in revision total knee arthroplasty (rTKA) utilizing a tibial trabecular metal (TM) cone. The purpose of this study was to compare: (1) functional outcomes, (2) radiographic outcomes and (3) implant survivorship in rTKA utilizing TM cones combined with either short stems (SS) or long stems (LS) at minimum 2 years follow-up. METHODS: In this retrospective, multi-centre study, patients undergoing rTKA utilizing a TM cone between 2008 and 2019 were included. Patients were divided into: SS group (no diaphyseal engagement), and LS group (diaphyseal engagement). All relevant clinical charts and post-operative radiographs were examined. Oxford Knee Score (OKS) and EuroQol-5D (EQ-5D-5L) data were collected at most recent follow-up. RESULTS: In total, 44 patients were included: 18 in the SS group and 26 in the LS group. The mean time of follow-up was 4.0 years. Failure free survival was 94.4% for the SS group and 92.3% for the LS group. All failures were for prosthetic joint infections managed with debridement, antibiotics, and implant retention. At most recent follow-up, 3 patients demonstrated radiographic signs of lucency (1 SS 2 LS, P = 1) and the mean OKS were 37 ± 4 and 36 ± 6 (P = 0.73) in the SS and LS groups, respectively. CONCLUSION: Tibial SS combined with TM cones performed as well as LS in rTKA at minimum 2 years follow-up. A tibial SS in combination with a TM cone is a reliable technique to achieve stable and durable fixation in rTKA.

Intraosseous Regional Administration of Prophylactic Antibiotics in Total Knee Arthroplasty.

Prosthetic joint infection (PJI) after total knee arthroplasty is a devastating complication. With the development of antibiotic resistance, a safe and effective means of delivering antibiotic prophylaxis is needed. Intraosseous regional antibiotics (IORA) achieve higher local concentrations of antibiotics with fewer systemic side effects. Previous studies have proven the safety of IORA, whereas animal models have proven it to be more effective than intravenous antibiotics for preventing infection following surgery. Recently, large-scale retrospective studies have also demonstrated lower PJI rates following TKA when IORA is used when compared to routine intravenous prophylaxis. In this article, we propose an evidence-based method for the administration of intraosseous antibiotics in TKA, cover the up-to-date data supporting its use, and explore future directions for additional research.

Differing Microorganism Profile in Early and Late Prosthetic Joint Infections Following Primary Total Knee Arthroplasty - Implications for Empiric Antibiotic Treatment.

BACKGROUND: Prosthetic joint infection (PJI) is the leading cause of revision following total knee arthroplasty (TKA). Prior to microorganism identification, the choice of the correct empiric antibiotics is critical to treatment success. This study aims to 1) compare the microorganism and resistance profile in early and late PJIs; 2) recommend appropriate empiric antibiotics. METHODS: A multicentre retrospective review was performed over a 15-year period. First episode PJIs were classified by both the Tsukayama Classification and Auckland Classification. For each PJI case, the causative organism and antibiotic sensitivity were recorded. RESULTS: Of eligible patients, 232 culture-positive PJI cases were included. Using either classification system, early PJIs (<4 weeks or <1 year since primary) were significantly more likely to be resistant and polymicrobial. The predominant organisms were coagulase-negative Staphylococci in early PJIs while Staphylococcus aureus was the most common in late PJIs. The distribution of gram-negative cases was higher in early Class-A than late Class-C PJIs (25% versus 6%, P = .004). Vancomycin provided significantly superior coverage when compared to Flucloxacillin for early infections, and addition of a gram-negative agent achieved coverage over 90% using both classification systems. CONCLUSION: Based on the microbiological pattern in Tsukayama criteria, Vancomycin with the consideration of Gram-negative agent should be considered for Class-A infections given the high proportion of resistant and polymicrobial cases. For Class-C infections, Cephazolin or Flucloxacillin is likely sufficient. We recommend antibiotics to be withheld in Class-B infections until cultures and sensitivities are known.

Risk Prediction of Major Adverse Cardiovascular Events Occurrence Within 6 Months After Coronary Revascularization: Machine Learning Study.

BACKGROUND: As a major health hazard, the incidence of coronary heart disease has been increasing year by year. Although coronary revascularization, mainly percutaneous coronary intervention, has played an important role in the treatment of coronary heart disease, major adverse cardiovascular events (MACE) such as recurrent or persistent angina pectoris after coronary revascularization remain a very difficult problem in clinical practice. OBJECTIVE: Given the high probability of MACE after coronary revascularization, the aim of this study was to develop and validate a predictive model for MACE occurrence within 6 months based on machine learning algorithms. METHODS: A retrospective study was performed including 1004 patients who had undergone coronary revascularization at The People's Hospital of Liaoning Province and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from June 2019 to December 2020. According to the characteristics of available data, an oversampling strategy was adopted for initial preprocessing. We then employed six machine learning algorithms, including decision tree, random forest, logistic regression, naïve Bayes, support vector machine, and extreme gradient boosting (XGBoost), to develop prediction models for MACE depending on clinical information and 6-month follow-up information. Among all samples, 70% were randomly selected for training and the remaining 30% were used for model validation. Model performance was assessed based on accuracy, precision, recall, F1-score, confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), and visualization of the ROC curve. RESULTS: Univariate analysis showed that 21 patient characteristic variables were statistically significant (P<.05) between the groups without and with MACE. Coupled with these significant factors, among the six machine learning algorithms, XGBoost stood out with an accuracy of 0.7788, precision of 0.8058, recall of 0.7345, F1-score of 0.7685, and AUC of 0.8599. Further exploration of the models to identify factors affecting the occurrence of MACE revealed that use of anticoagulant drugs and course of the disease consistently ranked in the top two predictive factors in three developed models. CONCLUSIONS: The machine learning risk models constructed in this study can achieve acceptable performance of MACE prediction, with XGBoost performing the best, providing a valuable reference for pointed intervention and clinical decision-making in MACE prevention.

Novel Growth Factor Combination for Improving Rotator Cuff Repair: A Rat In Vivo Study.

BACKGROUND: The lack of healing at the repaired tendon-bone interface is an important cause of failure after rotator cuff repair. While augmentation with growth factors (GFs) has demonstrated promise, the ideal combination must target all 3 tissue types at the tendon-bone interface. HYPOTHESIS: The GF combination of transforming growth factor beta 1, Insulin-like growth factor 1, and parathyroid hormone will promote tenocyte proliferation and differentiation and improve the biomechanical and histological quality of the repaired tendon-bone interface. STUDY DESIGN: Controlled laboratory study. METHODS: In vitro, human tenocytes were cultured in the presence of the GF combination for 72 hours, and cell growth assays and the expression of genes specific to tendon, cartilage, and bone were analyzed. In vivo, adult rats (N = 46) underwent detachment and repair of the left supraspinatus tendon. A PVA-tyramine gel was used to deliver the GF combination to the tendon-bone interface. Histological, biomechanical, and RNA microarray analysis was performed at 6 and 12 weeks after surgery. Immunohistochemistry for type II and X collagen was performed at 12 weeks. RESULTS: When treated with the GF combination in vitro, human tenocytes proliferated 1.5 times more than control (P = .04). The expression of scleraxis increased 65-fold (P = .013). The expression of Sox-9 (P = .011), type I collagen (P = .021), fibromodulin (P = .0075), and biglycan (P = .010) was also significantly increased, while the expression of PPARγ was decreased (P = .007). At 6 and 12 weeks postoperatively, the quality of healing on histology was significantly higher in the GF group, with the formation of a more mature tendon-bone interface, as confirmed by immunohistochemistry for type II and X collagen. The GF group achieved a load at failure and Young modulus >1.5 times higher at both time points. Microarrays at 6 weeks demonstrated upregulation of genes involved in leukocyte aggregation (S100A8, S100A9) and tissue mineralization (Bglap, serglycin, Fam20c). CONCLUSION: The GF combination promoted protendon and cartilage responses in human tenocytes in vitro; it also improved the histological appearance and mechanical properties of the repair in vivo. Microarrays of the tendon-bone interface identified inflammatory and mineralization pathways affected by the GF combination, providing novel therapeutic targets for further research. CLINICAL RELEVANCE: The use of this GF combination is translatable to patients and may improve healing after rotator cuff repair.

Modelling gluteus medius tendon degeneration and repair in a large animal model.

INTRODUCTION: Gluteus medius tendon tears often occur in the context of chronic tendinopathy and remain a difficult clinical problem. Surgical repair is challenging as it is often delayed and performed in degenerative tendons. No animal model currently exists to mimic the delayed repair of tendinopathic gluteus medius tears. The aims of this study were to develop a chronic model of gluteus medius tendinopathy and tear and then compare this model to an acute gluteus medius tear and repair. MATERIALS AND METHODS: Six gluteus medius muscles were dissected and examined in mature sheep to confirm anatomical similarity to the human counterpart. Ten separate adult sheep underwent tendon detachment, followed by relook and histological sampling at 6 and 16 weeks to assess the extent of tendon degeneration. Six adult sheep underwent tendon repair at 6 weeks and were later assessed for healing of the tendon and compared to a further four adult sheep who underwent an acute tendon detachment and repair procedure. RESULTS: The sheep gluteus medius muscle consisted of three compartments, the anterior, middle and posterior. All compartments inserted via the common tendon on the superolateral aspect of the greater trochanter. At both 6 and 16 weeks, there was significant tendinopathic changes on histology compared to controls as assessed by modified Movin's score (p = 0.018, p = 0.047) but no difference between the 6- and 16-week groups (p = 0.25). There were significant differences between delayed and acute repair in both histological appearance (p = 0.025) and biomechanical properties (p = 0.019), with acute repair superior in both. CONCLUSIONS: Tendon detachment for 6 weeks is sufficient to produce histological changes similar to chronic tendinopathy and repair of this degenerative tendon results in significantly poorer healing when compared to an acute repair model. Animal models for gluteus medius tears should use a delayed repair model to improve clinical validity.

Comparing uncemented, hybrid and cemented primary total hip arthroplasty in young patients, a New Zealand Joint Registry study.

BACKGROUND: Despite increasing use of uncemented implants in young patients undergoing total hip arthroplasty (THA), there is minimal evidence for specific implant combinations in this group. We analysed the most commonly used uncemented (Corail-Pinnacle), hybrid (Exeter-Trident/Tritanium), and fully cemented (Exeter) implant combinations in the New Zealand Joint Registry (NZJR) in patients aged under 40 and between 40 and 55 years. METHODS: All THAs recorded in the NZJR between 1999 and 2018 were included. The 40-55 and < 40 age groups were analysed separately. Demographic data, implant type, and outcome data including implant survival, reason for revision, and post-operative Oxford Hip Scores were obtained from the NZJR, and detailed survival analyses were performed. The primary outcome was revision for any reason. RESULTS: We identified 4152 THAs in the 40-55 group and 422 in the < 40 group. In the 40-55 group, revision rates and patient-reported outcome measure scores were comparable between the uncemented implant combination (0.70/100 component years) and the hybrid implant combination (0.62/100 component years), whereas the cemented implant combination exhibited a statistically significant higher revision rate (1.75/100 component years) (p < 0.001). In the < 40 group, revision rate for the hybrid implant combination (0.46/100 component years) was significantly lower than the uncemented implant combination (1.54/100 component years). CONCLUSION: The most commonly used hybrid and uncemented implant combinations provided equivalent survival and functional outcomes in patients aged 40-55 years. More research is required to guide implant selection in patients aged < 40 years. The authors suggest a transition away from comparing classes of implants (cemented, uncemented, hybrid) given the diverse product range within these categories.

Differential Responses of Transplanted Stem Cells to Diseased Environment Unveiled by a Molecular NIR-II Cell Tracker.

Stem cell therapy holds high promises in regenerative medicine. The major challenge of clinical translation is to precisely and quantitatively evaluate the in vivo cell distribution, migration, and engraftment, which cannot be easily achieved by current techniques. To address this issue, for the first time, we have developed a molecular cell tracker with a strong fluorescence signal in the second near-infrared (NIR-II) window (1,000-1,700 nm) for real-time monitoring of in vivo cell behaviors in both healthy and diseased animal models. The NIR-II tracker (CelTrac1000) has shown complete cell labeling with low cytotoxicity and profound long-term tracking ability for 30 days in high spatiotemporal resolution for semiquantification of the biodistribution of transplanted stem cells. Taking advantage of the unique merits of CelTrac1000, the responses of transplanted stem cells to different diseased environments have been discriminated and unveiled. Furthermore, we also demonstrate CelTrac1000 as a universal and effective technique for ultrafast real-time tracking of the cellular migration and distribution in a 100 µm single-cell cluster spatial resolution, along with the lung contraction and heart beating. As such, this NIR-II tracker will shift the optical cell tracking into a single-cell cluster and millisecond temporal resolution for better evaluating and understanding stem cell therapy, affording optimal doses and efficacy.

Smart Self-Assembly Amphiphilic Cyclopeptide-Dye for Near-Infrared Window-II Imaging.

Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near-infrared window (NIR-II, 1000-1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH-sensitive self-assembling cyclopeptide-dye, SIMM1000, as a smart nanoprobe for NIR-II imaging of diseases in living animals, is reported. This small molecule assembled nanoprobe exhibits smart properties by responding to a sharp decrease of pH in the tumor microenvironment (pH 7.0 to 6.8), aggregating from small nanoprobe (80 nm at pH 7.0) into large nanoparticles (>500 nm at pH 6.8) with ≈20-30 times enhanced fluorescence compared with the non-self-assembled CH-4T. It yields micrometer-scale resolution in blood vessel imaging and high contrast and resolution in bone and tumor imaging in mice. Because of its self-aggregation in acidic tumor microenvironments in situ, SIMM1000 exhibits high tumor accumulation and extremely long tumor retention (>19 days), while being excretable from normal tissues and safe. This smart self-assembling small molecule strategy can shift the paradigm of designing new nanomaterials for molecular imaging and drug development.

Infection and periprosthetic fracture are the leading causes of failure after aseptic revision total knee arthroplasty.

AIM: The purpose of this study was to clarify the medium to long term survival of aseptic revision total knee arthroplasty (RTKAs) and identify the common modes of failure following RTKAs. MATERIALS AND METHODS: A multi-center, retrospective study included all aseptic RTKAs performed at three tertiary referral hospitals between 2003 and 2016. Patients were excluded if the revision was for prosthetic joint infection (PJI) or they had previously undergone revision surgery. Minor revisions not involving the tibial or femoral components were also excluded. Demographics, surgical data and post-operative outcomes were recorded and analyzed. Survival analysis was performed and the reasons for revision failure identified. RESULTS: Of 235 aseptic RTKAs identified, 14.8% underwent re-revision at mean follow-up of 8.3 years. Survivorship of RTKA was 93% at 2 years and 83% at 8 years. Average age at revision was 72.9 years (range 53-91.5). The most common reasons for failure following RTKA were periprosthetic joint infection (PJI) (40%), periprosthetic fracture (25.7%) and aseptic loosening (14.3%). Of those whose RTKA failed, the average survival was 3.33 years (8 days-11.4 years). No demographic or surgical factors were found to influence RTKA survival on univariate or multivariate analysis. CONCLUSION: PJI and periprosthetic fracture are the leading causes of re-revision surgery following aseptic revision TKA. Efforts to improve outcomes of aseptic revision TKA should focus on these areas, particularly prevention of PJI.

Sustained Delivery of Lactoferrin Using Poloxamer Gels for Local Bone Regeneration in a Rat Calvarial Defect Model.

Lactoferrin (LF) is a multifunctional milk glycoprotein that promotes bone regeneration. Local delivery of LF at the bone defect site is a promising approach for enhancement of bone regeneration, but efficient systems for sustained local delivery are still largely missing. The aim of this study was to investigate the potential of the poloxamers for sustained delivery of LF to enhance local bone regeneration. The developed LF/poloxamer formulations were liquid at room temperature (20 °C) transforming to a sustained releasing gel depot at body temperature (37 °C). In vitro release studies demonstrated an initial burst release (~50%), followed by slower release of LF for up to 72 h. Poloxamer, with and without LF, increased osteoblast viability at 72 h (p < 0.05) compared to control, and the immune response from THP-1 cells was mild when compared to the suture material. In rat calvarial defects, the LF/poloxamer group had lower bone volume than the controls (p = 0.0435). No difference was observed in tissue mineral density and lower bone defect coverage scores (p = 0.0267) at 12 weeks after surgery. In conclusion, LF/poloxamer formulations support cell viability and do not induce an unfavourable immune response; however, LF delivery via the current formulation of LF200/poloxamer gel did not demonstrate enhanced bone regeneration and was not compatible with the rat calvarial defect model.

Factors predicting repeat revision and outcome after aseptic revision total knee arthroplasty: results from the New Zealand Joint Registry.

PURPOSE: The number of Revision TKAs performed continues to increase; however there is limited data on risk factors for failure. Additionally, clinical decisions regarding when and how to revise a failed TKA may be as important as the technical aspects of the procedure. The purpose of this study was to analyze factors predicting repeat revision following aseptic revision TKA. METHODS: Of 85,769 primary TKAs recorded on the New Zealand National Joint Registry, 1720 patients undergoing subsequent revision for aseptic indications between January 1999 and December 2015 were identified. Re-revision was recorded in 208 patients (12.1%). The analysis included demographic characteristics, surgeon revision case volume, surgical time, surgical ownership of index TKA as independent variables using logistic and linear regression. The primary outcome measure was incidence of subsequent re-revision and Oxford Knee Scores of revised TKAs (OKS). The secondary outcome measure was the influence of component exchange in major revisions on re-revision rate. RESULTS: Younger patients undergoing a revision (HR 0.974) and male gender (HR 0.666) were predictors of re-revision. Elapsed time since index surgery (unstandardized coefficient 0.060) and lower ASA score (UC - 2.749) were significant predictors of OKS. Femoral component revision was a predictor of re-revision (HR 1.696) and had the lowest OKS, compared to tibial and all component revision (p = 0.003). CONCLUSIONS: Repeat revision TKA is a rare and complex procedure influenced by a number of confounding factors. Using raw registry data, younger and male patients were found to be at a higher risk of re-revision after aseptic revision TKA. A longer time between primary TKA and revision was associated with better clinical outcomes. Isolated femoral component exchange led to worse outcomes both in terms of survivorship and functional scores. LEVEL OF EVIDENCE: III.